PED5 INHIBITOR SEMI-SOLID COMPOSITIONS AND METHODS OF MAKING AND USING THEREOF

Abstract

A chewable composition comprising an active pharmaceutical ingredient (API) composition, a surfactant composition, a binding composition, and a gelling composition in a sufficient amount to provide a cohesive gelled product. The API composition comprises a PED5 inhibitor; the surfactant composition and the API composition have a weight ration from about 0.1 to about 15; and the binding composition comprises a mono- or di-saccharide, a sugar alcohol, an oligosaccharide, or a combination thereof. In one embodiment, the API composition comprises tadalafil, sildenafil, vardenafil, avanafil, or a combination thereof.

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Claims

1. A chewable composition, comprising, an active pharmaceutical ingredient (API) composition, comprising a PED5 inhibitor, a surfactant composition, wherein the surfactant composition and the API composition have a weight ration from about 0.1 to about 15, a binding composition, comprising a mono- or di-saccharide, a sugar alcohol, an oligosaccharide, or a combination thereof, and a gelling composition in a sufficient amount to provide a cohesive gelled product.

2. The chewable composition of claim 1, wherein the API composition comprises tadalafil, sildenafil, vardenafil, avanafil, or a combination thereof.

3. The chewable composition of claim 1, wherein the API composition comprises tadalafil from about 2 mg to about 20 mg per dose.

4. The chewable composition of claim 1, wherein the surfactant composition comprises tween 80, sodium dodecyl sulfate, alpha Tocopherol, benzalkonium chloride, benzyl alcohol, cetostearyl Alcohol, cetrimide, cetylpyridinium chloride, docusate dodium, glyceryl monostearate, glyceryl palmitostearate, linoleic acid, macrogol 15 hydroxystearate, myristic acid, myristyl alcohol, macrogol cetostearyl ether, macrogol lauryl ether, macrogol oleyl ether, macrogol stearyl ether, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polyoxyethylene stearates, polyoxyl 40 stearate, caprylocaproyl macrogolglycerides, lauroyl macrogolglycerides, linoleoyl macrogolglycerides, oleoyl macrogolglycerides, stearoyl macrogolglycerides, polyoxylglycerides, sodium stearyl fumarate, sorbitan esters (sorbitan fatty acid esters), sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan stearate, sorbitan trioleate, sorbitan sesquioleate, stearic acid, stearyl alcohol, or a combination thereof.

5. The chewable composition of claim 1, comprising from 0.1% to 10% by weight of the surfactant composition.

6. The chewable composition of claim 1, wherein the ratio of the API composition and the surfactant composition is from 8 to about 12.

7. The chewable composition of claim 1, further comprising a complexing agent, wherein the complexing agent comprises cyclodextrin, a nucleotide, resistant starch, an amide, a peptide, or a combination thereof.

8. The chewable composition of claim 1, wherein the binding composition comprises glucose, sucrose, fructose, or a combination thereof.

9. The chewable composition of claim 1, further comprising a polymer stabilizer, and wherein the polymer stabilizer comprises a polymer of glucose monomer or mannose monomer linked through glycosidic bonds, wherein the glycosidic bond is substantially free of 1,4-alpha-glycosidic bond, and wherein the binding composition is essentially free of glucose, sucrose, or fructose, wherein the chewable composition.

10. The chewable composition of claim 10, wherein the binding composition comprises sugar alcohol.

11. The chewable composition of claim 10, wherein the binding composition comprises allulose, isomaltose, trehalose, tagatose, raffinose, or a combination thereof.

12. The chewable composition of claim 1, wherein the gelling composition comprises gelatin, starch, pectin, gellan gum, guar gum, tapioca, protein, alginin, gum Arabic, carrageenan, guar, agar, agar-agar, carboxymethylcellulose, hydroxyethylcellulose, sago, alginate, locust bean gum, xanthan gum, or derivatives thereof.

13. The chewable composition of claim 1, wherein the gelling composition comprises pectin having a methoxyl content of less than 15% by weight of pectin.

14. The chewable composition of claim 1, wherein the gelling composition comprises pectin having an amide content of more than 20% by weight of pectin.

15. The chewable composition of claim 1, wherein the gelling composition comprises pectin, gelatin, collagen, or a combination thereof.

16. The chewable composition of claim 1, wherein the gelling composition comprises pectin and collagen in a ratio from about 1:1 to about 1:3.

17. The chewable composition of claim 1, further comprising an herb composition, an antioxidant composition, a vitamin composition, a mineral composition, an amino acid composition, a probiotics composition, or a prebiotics composition.

18. The chewable composition of claim 19, further comprising an additive selected from sweeteners, food acids, flavoring agents, coloring agents, humectants, bulking agents, fatty acids, triglycerides, plasticizers, thickeners, preservatives, or and a mixture thereof.

19. The chewable composition of claim 1, wherein the gelling composition comprises pectin, wherein the pH of the composition is more than 4.

20. A method of making the chewable composition of claim 1, comprising, dividing the binding composition into a first binding portion and a second binding portion, combining a first mixture and water and heating to at a first elevated temperature to provide a first solution, wherein the first mixture comprises the first binding portion, combining the second mixture and water at a second elevated temperature to provide a second solution, wherein the second mixture comprises the gelling composition, the second binding portion, and the complexing agent, wherein the second binding portion is at least twice the mass of the gelling composition, mixing the second solution into the first solution at a third elevated temperature to provide a third mixture, wherein the third mixture has a Brix number from about 78 to about 86, and adjusting pH of the third solution with a buffer salt to from about 3 to about 7.

21. The method of claim 20, wherein the first mixture further comprises a polymer stabilizer.

22. The method of claim 20, wherein the second mixture or the third mixture further comprises the API composition, the surfactant composition or both.

23. The method of claim 20, further comprising the step of adding a coloring agent, a flavoring agent, or a combination thereof into the third mixture to provide a molding mix having a Brix from about 78 to about 86.

24. The method of claim 20, further comprising adding the API composition and the surfactant composition to the molding mixture.

25. A method for treating erectile dysfunction in a subject, benign prostatic hyperplasia in a subject, or pulmonary arterial hypertension in a subject or comprising administrating an effective amount of the chewable composition of claim 1 to the subject.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0092] The foregoing and other features of this disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments arranged in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:

[0093] FIG. 1 shows the chemical structure of tadalafil;

[0094] FIG. 2 shows, from top to bottom, representative non-ionic, anionic, cationic, and zwitterionic surfactants;

[0095] FIG. 3 shows the capture of tadalafil by the hydrophobic interior of a micelle;

[0096] FIG. 4 shows the chelation of a drug by cyclodextrin;

[0097] FIG. 5 shows a representative amide resonance; and

[0098] FIG. 6 shows the association of tadalafil with N-acetylglucosamine through the amide moiety, in which the nitrogen with a partial positive charge associates with the oxygen with a partial negative charge, the association of the two amide groups results in a six-member ring, one association is shown for clarity and either one (on either amide tadalafil amide) or two associations are possible.

DETAILED DESCRIPTION

[0099] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.

[0100] This disclosure is generally drawn, inter alia, to compositions, methods, and processes related to semi-solid chewable composition.

[0101] As used herein, semi-solid chewable gel composition, chewable composition and gummy composition are used interchangeably.

[0102] As used herein, allulose and psicose are used interchangeably.

[0103] As used herein, isomaltulose and palatinose are used interchangeably.

[0104] As used herein, mix and mixture may be used interchangeably.

[0105] In one embodiment, the chewable composition comprising an active pharmaceutical ingredient (API) composition comprising a PED5 inhibitor, a surfactant composition, wherein the surfactant composition and the API composition have a weight ration from about 0.1 to about 15, a binding composition, comprising a mono- or di-saccharide, a sugar alcohol, an oligosaccharide, or a combination thereof, and a gelling composition in a sufficient amount to provide a cohesive gelled product.

[0106] Active Pharmaceutical Ingredients (APIs)

[0107] In one embodiment, the API composition comprises tadalafil, sildenafil, vardenafil, avanafil, or a combination thereof. In one embodiment, the API composition comprises tadalafil. In one embodiment, the API composition comprises sildenafil. In one embodiment, the chewable composition comprises from 0.16% to 0.63% w/w of the API composition.

[0108] Gummy can be used as an efficient delivery mechanism for an API. Firstly, gummy composition is easy to consume especially for patient populations having swallowing difficulty including without limitation pediatric and geriatric population. Second, gummy, if formulated to taste good, increases patient's compliance in taking medication. Third, when being consumed, gummy composition dissolves and coats the mucosal membrane allowing for direct absorption of APIs through a trans-mucosal process, potentially bypassing the digestion track and reducing first-pass effect.

[0109] A good tasting gummy product has the advantage of being palatable and convenient to consume, leading to increased patients' compliance in taking the medication. The act of chewing and dissolving the gummy allows for trans-mucosal absorption of the API directly into blood circulation for fast action and bypassing the liver and avoiding first-pass effect.

[0110] Gummy has not been used for the delivery of active pharmaceutical ingredient(s) (API). One reason is that many APIs are extremely foul or bitter in taste. Tadalafil is one example. The inclusion of the API may lead to a foul-tasting product. Hence, pharmaceuticals have typically been reserved for non-chewable items that make for minimal mouth contact. Thus, a major advancement in API delivery is a delivery mechanism that allows chewing and mouth contact with little to none of the bitterness or medicinal taste of the API. This disclosure gives a delivery mechanism for the PED5 inhibitor that eliminates the bitterness and medical taste of the API allowing the formulation to be chewed.

[0111] Tadalafil is a type-V phosphodiesterase (PDE-5) inhibitor that increases blood flow to genital parts of the body. Tadalafil is indicated for erectile dysfunction, sexual dysfunction, and certain cardiac symptoms. Tadalafil is also known as Cialis. Tadalafil is bitter and unpleasant tasting.

[0112] In one embodiment, the gummy formulation for the delivery of tadalafil is presented. The gummy delivers 2.5, 5, 10 20 mg, or 40 mg of tadalafil in a format that has a pleasing taste. In one embodiment, the gummy consists of a gelling agent, sugars, water, and complexing agents that chelates tadalafil. Tadalafil is coordinated in the gummy structure which leads to a reduction or elimination of the unpleasant perception of the tadalafil API. The tadalafil gummy allows for fast absorption and faster relief of symptoms.

[0113] The chemical structure for tadalafil is shown in FIG. 1. The IUPAC name for tadalafil is 2R,8R)-2-(1,3-benzodioxol-5-yl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.0.sup.3,8.0.sup.11,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione.

[0114] Tadalafil functions by increasing the level of the cyclic guanosine-3,5-monophosphate (cGMP), which is an important secondary messenger that controls many physiological processes. The level of intracellular cGMP is determined by the activities of the cyclase enzyme which produces it, and the type-V phosphodiesterase (PDE-5) that degrades it. The inhibition of PDE-5 increases the level of cGMP, and therefore can be used in a therapeutic strategy for male erectile dysfunction, and also for the treatment of cardiovascular diseases.

[0115] Surfactants

[0116] Applicant discovered that surfactants are useful with improving flavor and stability of tadalafil gummy formulation. Surfactants are molecules with amphiphilic properties. Surfactants form micelles when added to water. The interior of the micelle is hydrophobic whereas the exterior is hydrophilic. Micelles have the ability to dissolve hydrophobic materials and suspend them in water forming emulsions.

[0117] There are many types of surfactants: cationic, anionic, zwitterionic, or non-ionic. Cationic examples include ammonium or pyridinium; anionic examples include carboxylates, sulfonates, sulfates, and phosphates; zwitterionic examples include tetraalkyl ammonium carboxylates, tetraalkyl ammonium sulfates, and ammonium phosphates, while non-ionic include polyethers, and alcohols. The concept of surfactants is shown in FIG. 2.

[0118] One problem that needs to be solved for using surfactants is the pH of the gummy. Gummies are typically acidic and have a typical pH range from a pH of 2.5 to pH of 4. If the pKa of the surfactant is higher that the pH of the gummy then the surfactant may become non-functional and precipitate. For example, the pKa of stearic acid, of which sodium stearate is a surfactant, is 4.75. At a pH above the pKa the sodium stearate surfactant is ionized and functions well, but below a pH below the pKa the stearate is protonated to stearic acid which is insoluble in water and the surfactant precipitates. Thus, the pKa of the surfactant needs to be below the acidity of the gummy formulation. In one embodiment, the surfactants are sulfonates and/or sulphate surfactants since their pKa's are typically below 0. The phosphate surfactants with pKa is below 2 can be useful. Non-ionic surfactants and zwitterionic surfactants can also be useful if they are stable in a high ionic strength medium.

[0119] Surfactants are particularly well suited to capturing molecules inside their micelles; especially hydrophobic molecules such as Tadalafil. Applicant found that the addition of a surfactant helps to solubilize tadalafil into water and make it more accessible to the cyclodextrin molecules to chelate. FIG. 3 illustrates the process of tadalafil uptake by micelles formed from surfactants. While tadalafil is practically insoluble, there is a small, mol fraction solubility (5.74.Math.10E-7 at 298.15 K) in water. The tadalafil that solubilizes is captured by the micelles. By Le Chatelier's principle the capture of tadalafil by micelles leads to more tadalafil being solubilized by water which in turn leads to more capture by micelles. In this way the micelles help to dissolve the tadalafil.

[0120] The micelles help the flavor profile and stability of tadalafil gummies. In initial water solution the tadalafil is surrounded by the surfactant, which keeps the drug away from the taste buds on the tongue. The surfactant can aid in the transfer of tadalafil to the complexing agent, such as cyclodextrin, as the gummy becomes increasingly rich in carbohydrates during the formation process.

[0121] Complexing Agents

[0122] Complexing agents may be useful to complex with API masking or modulating flavor profile, reducing bitterness, increasing the solubility of the API, or increasing the stability of the formulation. In one embodiment, the complexing agent may form an inclusion complex with API. In one embodiment, the complexing agent comprises cyclic glucose (i.e. cyclic dextrin).

[0123] Cluster dextrin have a ring structure with many branches of long chains of glucose units pendent to the ring forming a helical structure. The helical structure along with the ring structure of cluster dextrin are both able to chelate small molecules such as, at least partially, tadalafil. The chelation takes place by the aromatic rings of tadalafil fitting inside the helical structure.

[0124] There are three major forms of cyclodextrin: alpha, beta, and gamma. Alpha cyclodextrin consists of a ring of 6 glucose units while beta has 7 glucose units in a ring and gamma has 8 glucose units in a ring. The ring structures form a crown. The inside of the crown is able to chelate small molecules; especially hydrophobic molecules.

[0125] The chelation of a drug by cyclodextrin is shown in FIG. 4. The aromatic group of tadalafil may fit inside the cyclodextrin ring structure. The inside cavity of the cyclodextrin structure is largely hydrophobic, which is favorable for complexing aromatic systems that are also hydrophobic. The formation of the chelate structure is endothermically favorable due to electrostatic interactions of the p system of the aromatic moiety within the hydrophobic cavity and electronic interaction with the hydrogen atoms and glycidyl ether bonds. It is these electronic interactions between these systems of the cyclodextrin and the pi system that gives the favorable heat of formation. The alpha, beta, and gamma cyclodextrins do not form the complex with tadalafil equally. Tadalafil forms stable complexes with all the cyclodextrins with gamma being the most stable complex and alpha being the least stable.

[0126] The coordination of tadalafil by cluster dextrin molecules is more by chance therefore the complexing efficiency may be low. Cluster dextrin molecules have a broad range of cyclic ring and helical structures. Statistically there are some cyclic and helical structures that meet the criteria for chelation of tadalafil.

[0127] An effective method of flavor mitigation for an API that has functionality similar in structure to nucleotide bases is the addition DNA or RNA or sources rich in RNA and DNA. The base structures on DNA consists of two purines and two pyrimidines. The purines are adenine and guanine while the two pyrimidines are cytosine and thymine.

[0128] A chemical structure such as tadalafil which has a pyrimidine-like structural unit will be naturally attracted and bind the purine bases in DNA thereby complexing the API and reducing its contribution to the overall flavor of the gummy. Foods that are particularly high in DNA are the fruits and vegetables and their powders. Fruits and vegetables have many strands of DNA and RNA that go beyond the normal helix (diploid). The strawberry is famous for being particularly rich in DNA. Each cell in a strawberry contains 8 copies of its genetic information (octoploid), while most animal cells only contain 2 copies (diploid). Other examples of high-density DNA and/or RNA are the sweet potato (hexaploid), sugar cane (octoploid), apple (triploid), peanut (tetraploid), and kumquats (tetraploid). Any polyploidy plant material can be used as the DNA/RNA source.

[0129] In one embodiment, the chewable composition further includes a complexing agent that coordinates (or complexes) with tadalafil. The complexing agent may be a cyclodextrin, a cluster dextrin, a nucleotide, a nucleic acid, or N-acetylglucosamine. Through extensive research, Applicant discovered with surprise that N-acetylglucosamine works to help reduce the bitterness or unpleasant flavors as well as the surfactant and cyclodextrin. The result is a tadalafil gummy that has excelling chew, taste, and flavor profile.

[0130] N-Acetylglucosamine is an amino sugar where the hydroxy moiety on carbon 2 has been substituted with an amino moiety and subsequently amidated with acetic acid. Amides have the chemical structure

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The chemical structure is such that there is an electron rich group, containing the nitrogen, adjacent to an electron deficient group, the carbonyl which contains the carbon and oxygen. Electron density can be transferred from the nitrogen to the carbonyl to form a resonance structure as shown in FIG. 5.

[0131] The resonance structure is a Zwitterionic form of the amide structure where there is a positive charge on the nitrogen, a negative charge on the oxygen and a double bond between the nitrogen and carbon atoms.

[0132] Tadalafil is also an amide, in fact, tadalafil has two amide structures. The amide structures that exist for N-acetylglucosamine also exist for tadalafil. The N-acetylglucosamine is able to associate with the tadalafil though the amide group as shown in FIG. 6. The association of N-acetylglucosamine with tadalafil through the amide moiety contributes to the reduction in the bitter medicinal taste.

[0133] Binding Composition

[0134] Binding composition binds the chewable (gummy) together through interaction with the gelling composition. The interaction may be through hydrogen bonding or through covalent bonding. In one embodiment, the binding composition comprises sugars, sugar derivatives, sugar alcohols, or a combination thereof. The binding composition may keep texture of the product soft by acting as a humectant.

[0135] In one embodiment, the binding composition comprises sucrose, glucose, fructose, or a combination thereof. In one embodiment, the chewable composition comprises from about 50% to about 90%, from about 60% to about 85% of the binding composition.

[0136] In one embodiment, the binding composition comprises a mono- or di-saccharide (i.e., sugar) having a glycemic index of less than 35, 30, 25, 20, 15, or 10, a sugar alcohol, or a combination thereof. In one embodiment, the chewable composition is substantially free of sugar having a glycemic index of more than 35. In one embodiment, the semi-solid chewable composition has a glycemic index of not more than 8, 10, 15 or 20.

[0137] In one embodiment, the chewable composition is substantially free of sucrose, fructose, glucose, sugar alcohol, sugar substitute, or non-sugar sweetener. Example sugar substitutes include, without limitation, sucralose, stevia extract or derivatives, monk fruit extract, licorice extract or derivative, tamarind extract or derivative, or their derivative thereof.

[0138] In one embodiment, the binding composition comprises a low GI sugar having a glycemic index (GI) of not more than 18, 20, 30 or 35. In one embodiment, the low GI sugar comprises allulose, sorbose, tagatose, trehalose, isomaltulose, raffinose, or a combination thereof. In one embodiment, the binding composition comprising tagatose, allulose (also known as allulose), sorbose, isomaltulose, trehalose (also known as mycose), mannose, maltose, ribose, xylose, tetroses, pentoses, hexoses, heptoses, their acid forms or a combination thereof. In one embodiment, the binding composition consists essentially of allulose, isomaltulose, and a third low GI sugar selected from a group consisting of trehalose, sorbose, tagatose, or a combination thereof. In one embodiment, the binding composition further comprises N-acetyl glucosamine.

[0139] Through extensive experimentation, processes are developed to used allulose, sorbose, tagatose, isomaltulose, trehalose in the gummy formulation allowing these sugars behave like conventional sugars such as sucrose and fructose but without the caloric significance of the convention sugars.

[0140] In one embodiment, the binding composition comprises allulose, trehalose and isomaltulose. In one embodiment, the binding composition comprises more than 20% isomaltulose. In one embodiment, the binding composition comprises from 15% to 35% isomaltulose. In one embodiment, the binding composition comprises not more than 75% of allulose. In one embodiment, the binding composition comprises from 45% to 60% allulose. In one embodiment, the binding composition comprises not more than 45% of trehalose.

[0141] In one embodiment, the binding composition comprises allulose and tagatose. In one embodiment, the binding composition comprises not more than 50% tagatose. In one embodiment, the binding composition comprises from 30% to 45% tagatose. In one embodiment, the binding composition comprises not more than 70% of allulose.

[0142] In one embodiment, the binding composition comprises isomaltulose and tagatose. In one embodiment, the binding composition comprises from 30% to 60% tagatose. In one embodiment, the binding composition comprises not more than 70% of isomaltulose.

[0143] Sugar alcohols are sweet, non-cariogenic, not digestible and provide fewer calories than many sugars. In some embodiments, sugar alcohols may mask other flavors. For example, mannitol may be used to mask bitterness Mannitol masks bitterness by a mechanism that involves the endothermic nature of mannitol dissolving into water.

[0144] In one embodiment, the binding composition comprises essentially of sugar alcohols. Example sugar alcohols include sorbitol, mannitol, erythritol, xylitol, isomalt, maltitol, lactitol, and hydrogenated starch hydrolysates. In one embodiment, the binding composition comprises mannitol, maltitol, or isomalt. In one embodiment, the binding composition comprises mannitol, sorbitol, isomalt, or a combination thereof. In one embodiment, the binding composition consists essentially of mannitol, maltitol, sorbitol, or a combination thereof. In one embodiment, the binding composition consists essentially of mannitol, maltitol, xylitol, or a combination thereof. In one embodiment, the binding composition consists essentially of mannitol, xylitol, isomalt, or a combination thereof. In one embodiment, the binding composition consists essentially of mannitol, xylitol, sorbitol or a combination thereof. In one embodiment, the binding composition consists essentially of mannitol, sorbitol, isomalt, resistant starch or a combination thereof. In one embodiment, the binding composition consists essentially of mannitol, maltitol, sorbitol, maltodextrin or a combination thereof. In one embodiment, the binding composition consists essentially of mannitol, sorbitol, or a combination thereof. In one embodiment, the binding composition consists essentially of mannitol, sorbitol, erythritol or a combination thereof.

[0145] Erythritol ((2R,3S)-Butan-1,2,3,4-tetrol) is a non-caloric polyol with a moderate sweetness of 60-80% of sucrose. Erythritol exhibits a cooling effect due to its negative heat of solution. Erythritol can improve the mouth feeling and mask certain unwanted aftertastes such as astringency and the irritant effect of intense sweeteners.

[0146] Sorbitol is highly soluble in water and is an excellent humectant. Xylitol not only non-cariogenic, it actually prevents tooth decay. Lactitol has about 30-40% of sugar's sweetening power. Its taste and solubility profile resemble sugar. Isomalt is 45-65% as sweet as sugar and does not tend to lose its sweetness or break down during the heating process. Isomalt absorbs little water. Maltitol is 75% as sweet as sugar and provides about 2-3 kcal/g. It gives a creamy texture to the formulation.

[0147] In one embodiment, the binding composition may include hydrogenated starch hydrolysates (HSH). HSH is a form of sugar alcohol from the hydrogenation of starch. The hydrogenation process yields a mixture of several sugar alcohols. HSH are nutritive sweeteners that provide 40-90% of the sweetness of sugar.

[0148] Gelling Composition

[0149] In one embodiment, the gelling composition comprises pectin, gelatin, or a combination thereof. In one embodiment, gelatin may be combined with other hydrocolloidspectin, agar, starch, gum Arabicto create desired textures. In one embodiment, gelatin may be combined with gum arabic as the gelling composition.

[0150] In one embodiment, the gelling composition comprises starch such as amylose starch or modified starch. There are a variety of starch modification techniques, such as contacting starch with acid, sodium or potassium hydroxide, or oxidizing the starch.

[0151] In one embodiment, the gelling composition comprises agar. Agar may be combined with locust bean gum as a gelling composition. Locust bean gum helps to prevent weeping of agar gels. The two polysaccharides from agar and locust bean gum synergistically interact with each other to form a strong gel that does not weep.

[0152] In one embodiment, the gelling composition comprises carageenans. Carrageenans or carrageenins are linear sulfated polysaccharides. Kappa-carrageenan has one sulphate group per disaccharide and forms strong, rigid gels in the presence of potassium ions. In one embodiment, locust bean gum may be used with kappa-carrageenan to prevent weeping. Gels formed from kappa-carrageenan and potassium ions are thermally reversible.

[0153] In one embodiment, the gelling composition comprises alginic acid or alginate. Alginate may form strong hydrogels when crosslinked with calcium ions.

[0154] Polymer Stabilizer

[0155] The polymer stabilizer serves to stabilize the chewable composition. In one embodiment, the polysaccharide may be water soluble.

[0156] In one embodiment, the polymer stabilizer comprises a polysaccharide of mono- or di-saccharide monomers. In one embodiment, the monomers may include glucose, fructose, mannose, galactose, arabinose, rhamnose, xylose, galacturonate, glucuronate, N-acetylgalactosamine, N-acetylglucosamine, or a combination thereof. The polysaccharide comprises from about 5 to about 50 monosaccharide monomers.

[0157] In one embodiment, the polymer stabilizer comprises polydextrose, resistant starch, cellulose, maltodextrin, resistant maltodextrin, beta-glycan, soluble fiber, inulin, oligofructose, mannan-oligosaccharide, mannose oligosaccharide, galacto-oligosaccahride, fructo-ligosaccharide, galactomannan oligomers, oligomers of ribose, xylose, arabinose, rhamnose, hyaluronic acid, or a combination thereof.

[0158] Maltodextrin is an oligiosaccharide consisting of 6-20 glucose units. Maltodextrin can be in digestible or resistant forms. Digestible maltodextrin consists of a chain of 6-20 glucose units connected by alpha-1,4-glycosidic bonds. Resistant maltodextrin consists of a chain of 6-20 glucose units connected through alpha-1,2, alpha-1,3, beta-1,2, beta-1,3, and/or beta-1,4 glycosidic bonds. As the name implies, resistant maltodextrin resists digestion as the enzyme amylase is inactive on the bonds that constitute resistant maltodextrin whereas amylase is active on the bonds that constitute maltodextrin. Maltodextrin provides for 4 Calories per gram whereas resistant maltodextrin provides for 1.6 Calories per gram. Applicant discovered that the inclusion of roughly 5% w/w maltodextrin can help stabilize the gummy products against crystallization.

[0159] In one embodiment, the polymer stabilizer may include a polysaccharide derived from an herb. In one embodiment, the polysaccharide may derive from Cistanche deserticola, Astragalus membranaceus, Rubia cordifolia, Nerium indicum, Adhatoda vasica, Withauia somnifera, and Glycyrrhiza glabra, aloe vera, Bletilla striata, Kobjar, Goji berry, elderberry, or a combination thereof.

[0160] In one embodiment, the polymer stabilizer may include a mushroom polysaccharide. In one embodiment, the mushroom polysaccharide may derive from schizophyllum commune (Schizophyllum commue), Brazilian mushroom (Agarics blaze), Cordyceps sinensis (Cordyceps sinensis), glossy ganoderma (Ganoderma lucidum), rainbow conk (Coriolus versicolor), camphor tree sesame (Anthodia camphorate), Phellinus (Phellinus linteus), coral mushroom (Pleurotus citrinopileatus), mushroom (Lentinula edodes), Liu Songgu (Agrocybe aegerita), Hericium erinaceus (Hericium erinaceus), pleurotus eryngii (Pleurotus eryngiig), petal fine and soft (Sparrasis crispa), black fungus (Auricularia auricula), Asparagus (Flammulina velutipes) or a combination thereof. In one embodiment, the mushroom polysaccharide may include chitin, hemicellulose, - and -glucans, mannans, xylansand, or galactans. In one embodiment, the mushroom polysaccharides may include -glucan polymers, with the main chain consisting of -(1.fwdarw.3) linkages with some -(1.fwdarw.6) branches as well as chitin, mannans, galactans, and xylans.

[0161] In one embodiment, the semi-solid composition may include from about 5% to about 15% of polymer stabilizer. In one embodiment, the ratio of the binding composition and the polymer stabilizer is from about 8:1 to about 20:1.

[0162] Coating Composition

[0163] The gummy pieces or semi-solid chewable composition disclosed herein may be coated with a coating composition. In one embodiment, the coating compositions may include sugar, sugar alcohol, or a combination thereof.

[0164] In one embodiment, the coating composition may include sucrose (sanding sugar).

[0165] For low sugar or sugar free composition, example sugars may include allulose, sorbose, tagatose, trehalose, and isomaltulose, or a combination thereof. Example sugar alcohols may include erythritol, sorbitol, mannitol, maltitol, isomalt, xylitol, or a combination thereof. In one embodiment, the coating composition comprises resistant starches, fibers, inulin, or a combination thereof in one embodiment, the coating composition may include matitol, isomalte, allulose, or a combination herein.

[0166] The chewable composition may further comprise an herb composition, an antioxidant composition, a vitamin composition, a mineral composition, an amino acid composition, a probiotics composition, or a prebiotics composition.

[0167] Herbal Composition

[0168] Herbal extract or derivatives useful for the application may include flavanoids, allied phenolic compounds, polyphenolic compounds, terpenoids, alkaloids, sulphur-containing compounds, polysaccharides, flavone, flavonoids, quinone, or combinations thereof. In one embodiment, the herbal composition may comprise an adaptagen.

[0169] Antioxidants

[0170] Antioxidant may include astaxanthin, carotenoids, coenzyme Q10 (CoQ10), flavonoids, glutathione, Goji (wolfberry), hesperidin, lacto-wolfberry, lignan, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin C, vitamin E, zeaxanthin, or combinations thereof.

[0171] Vitamins

[0172] Vitamins may include vitamin A, Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (niacin, inositol hexanicotinate or niacinamide), Vitamin B5 (pantothenic acid or pantothenic acid salt), Vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride), Vitamin B7 (biotin), Vitamin B9 (folic acid), and Vitamin B12 (various cobalamins, commonly cyanocobalamin in vitamin supplements), vitamin C, vitamin D, vitamin E, vitamin K, K1 and K2 (i.e., MK-4, MK-7), folic acid, biotin, choline, or combinations thereof.

[0173] Minerals

[0174] Minerals may include boron, calcium, chromium, copper, iodine, iron, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, selenium, silicon, tin, vanadium, zinc, amino acid chelated minerals, yeast cell wall chelated minerals, or combinations thereof.

[0175] Amino Acids

[0176] Amino acid may include for example alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, valine, taurine, theanine, carnitine, its derivative, or combinations thereof. In one embodiment, the amino acid may be a branched-chain amino acid. In one embodiment, the amino acid may be a natural amino acid. In one embodiment, the amino acid may be a non-natural amino acid.

[0177] Taurine, or 2-aminoethanesulfonic acid, is an amino acid that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to 0.1% of total human body weight. Taurine can reduce bitterness by 50% when added at a concentration of 300 mM.

[0178] Probiotics

[0179] The term probiotic is recognized in the state of the art as a microorganism which, when administered in adequate amounts, confers a health benefit to the host. A probiotic microorganism must fulfil several requirements related to lack of toxicity, viability, adhesion and beneficial effects.

[0180] Probiotic may include Aerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Micrococcus, Mucor, Oenococcus, Pediococcus, Penicillium, Peptostrepococcus, Pichia, Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus, Streptococcus, Torulopsis, Weissella, non-replicating microorganisms, or combinations thereof.

[0181] The chewable composition may contain probiotic strains in an amount ranging from 10.sup.5 and 10.sup.12 cfu/g. In one embodiment, the chewable comprises between 10.sup.7-10.sup.10 cfu/g.

[0182] Prebiotics

[0183] Useful prebiotics are Lactose, Inulin, Fructo oligosacccharides, Galacto oligosaccharides and Xylo oligosaccharides. Prebiotics are naturally found plenty in certain fruits like bananas, asparagus, garlic, tomato and onion wheat. The characteristic features of ideal prebiotics are as follows. They are neither to be hydrolysed nor absorbed by mammalian enzymes or tissues. They selectively enrich beneficial bacteria. The most important characteristic feature is that prebiotics can alter the intestinal micro-flora and its activities.

[0184] Prebiotics when combined with probiotics have many advantages. Basically, prebiotics selectively stimulate the growth of probiotics, which is dose and strain dependent. Prebiotics serve as a selective growth substrate for the probiotics strain during fermentation, during the period of storage, or during its passage through the gut.

[0185] Prebiotic may include for example acacia gum, alpha glucan, arabinogalactans, beta glucan, dextrans, fructooligosaccharides, fucosyllactose, galactooligosaccharides, galactomannans, gentiooligosaccharides, glucooligosaccharides, guar gum, inulin, isomaltooligosaccharides, lactoneotetraose, lactosucrose, lactulose, levan, maltodextrins, milk oligosaccharides, partially hydrolyzed guar gum, pecticoligosaccharides, resistant starches, retrograded starch, sialooligosaccharides, sialyllactose, soyoligosaccharides, sugar alcohols, xylooligosaccharides, their hydrolysates, or combinations thereof.

[0186] Humectants

[0187] A pharmaceutically acceptable humectant can include one or a mixture of humectants, such as, for example, glycerin, sorbitol and polyethylene glycol, for the gummy composition embodiments. The humectant content can be in the range of from about of 1% w/w to about 30% w/w and such as about 2% w/w to about 25% w/w.

[0188] Humectants are low molecular weight species that give the sensation of moisture in the gummy composition. The humectants mimic water in the gummy composition and which allows for very low water levels (2-6%) in the gummy composition. The humectant can act as a moisturizing agent in the mouth. The humectant prevents the gummy composition from drying out and helps to maintain softness and shelf life. A very low vapor press is an important property of the humectant for the maintenance of softens so it does not evaporate out. Example humectants are glycerol (glycerin, 1,2,3-propantriol), propylene glycol (1,2-propandiol), aloe vera gel, glyceryl triacetate, and a-hydroxyacids (lactic acid).

[0189] In one embodiment, the humectant comprises glycerol. Applicant notes that glycerol extends the shelf life of gummy composition by helping gummies retain their softness and chewability for longer period.

[0190] Sweeteners

[0191] Example sugar substitutes include saccharin, aspartame, sucralose and acesulfame K. In some embodiments, the sweetener used in the composition not only provides sweetness but also decreases the populations of bacteria in the mouth that lead to oral health problems.

[0192] In one embodiment, the sweetener is selected from one or more of saccharin, aspartame, cyclamate, sucralose, Stevia, mannitol, sorbitol, xylitol and similar glycols.

[0193] Plasticizers

[0194] Plasticizers impart flexibility by lowering the glass transition temperature of the polymers. They act in gummy composition decrease brittleness and increase chewiness. Some plasticizers that can be added to the chewable are lecithin, hydrogenated vegetable oils, glycerol mono, di and tri acetate ester, lanolin, methyl ester of the fatty acids, pentaerythritol mono, di, and tri acetate ester, rice bran wax, stearic acid, sodium and potassium stearates.

[0195] Flavoring Agents

[0196] A pharmaceutically acceptable flavoring agent can include one or a mixture of flavoring agents, such as for example bubble gum flavor, cherry flavor, grape flavor, anise oil, cassia oil, vanilla extract, vanilla creme, orange flavor, anethole, licorice, spearmint oil, phenylacetaldehyde diisobutyl acetal, and mixtures thereof, such as spearmint essential oil. Some flavoring agents can also act as sweeteners and can be use as such and include, for example, neohespiridin dehydrochalcone, xylitol, Sucralose, and mixtures thereof, such as xylitol. The flavoring agent content can be in the range of from about of 0.05% w/w to about 3% w/w and such as about 0.5% w/w to about 1% w/w.

[0197] Flavors and colors are for sensory appeal. Flavor components in gum exist in liquid, powder or micro-encapsulated forms. Liquid flavor incorporations are either water-soluble, oil-soluble, or water-dispersible emulsions. The oil-soluble flavors remain in the gum longer, resulting in longer lasting flavor sensations, because the gum base is hydrophobic and attracted to oil-based components. Conversely, water soluble flavors dissolve into saliva and as such are extract out of the gum which leads to quicker loss in flavor.

[0198] In one embodiment, the flavoring agent is a phenolic flavoring agent selected from eucalyptol, thymol, methyl salicylate, menthol, chlorothymol, phenol, wintergreen oil, spearmint oil, peppermint oil and similar essential oils, and halogenated and other derivatives thereof.

[0199] Flavoring Modulating Agents

[0200] Taurine, or 2-aminoethanesulfonic acid, is an organic compound that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to of total human body weight. Taurine can reduce bitterness by 50% when added at a concentration of 300 mM.

[0201] Coatings

[0202] A coating can be applied to the chewable composition. Alternatively, the gummy composition can be wrapped in wax paper. The coating can include sugars such allulose, sorbose, tagatose, trehalose, and isomaltulose or sugar alcohols such as erythritol, sorbitol, mannitol, maltitol, isomalt, and xylitol. Resistant starches may also be used for coating.

[0203] Preservatives

[0204] A pharmaceutically acceptable preservative can include one or a mixture of preservatives, such as, for example, benzoic acid, sodium benzoate, methylparaben, propylparaben, sorbic acid and potassium sorbate. These preservative may present at levels ranging from about 0.01% w/w to about 2% w/w.

EXAMPLES

Example. Tadalafil Low GI Pectin Gummy

[0205] 78.0 grams pectin; 1020.5 grams Allulose; 538.0 grams Trehalose, 362.0 grams Ismaltulose, 30.0 grams, Mannitol, 3.0 grams Sodium Citrate; 35.0 grams beta-cyclodextrin; 150 grams Maltodextrin, 10.00 grams Tadalafil; Sodium Dodecyl Sulfate, Citric Acid; Malic Acid; CFR Title 21 Granular Pineapple Flavor; CFR Title 21 FD&C Yellow.

[0206] In a separate container is added the allulose, trehalose, isomaltulose, maltodextrin, and mannitol. The carbohydrates are combined and mixed until homogeneous. This is mix 1. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. In a separate container is added the tadalafil, sodium dodecyl sulfate and sodium citrate. This is mix 2. water is added to a container and heated to 99 C. Mix 2 is added and stirred. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin mixture is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Tadalafil Low GI Pectin Gummy

[0207] 75.0 grams pectin; 1020.5 grams Allulose; 538.0 grams Trehalose, 362.0 grams Ismaltulose, 30.0 grams, Mannitol, 3.0 grams Sodium Citrate; 35.0 grams beta-cyclodextrin; 200 grams Maltodextrin, 6.0 grams Tadalafil; Sodium Dodecyl Sulfate, Citric Acid; Malic Acid; CFR Title 21 Granular Pineapple Flavor; CFR Title 21 FD&C Yellow.

[0208] In a separate container is added the allulose, trehalose, isomaltulose, maltodextrin, and mannitol. The carbohydrates are combined and mixed until homogeneous. This is mix 1. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. In a separate container is added the tadalafil, sodium dodecyl sulfate and sodium citrate. This is mix 2. water is added to a container and heated to 99 C. Mix 2 is added and stirred for 2 hours. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin mixture is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free Tadalafil Gummy

[0209] 75.0 grams pectin; 1050.5 grams Maltitol; 840.5 grams Isomalt, 180 grams Maltodextrin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams beta-cyclodextrin; 10.00 grams Tadalafil, Sodium Dodecyl Sulfate, Citric Acid; Malic Acid; CFR Title 21 Granular Pineapple Flavor; CFR Title 21 FD&C Yellow Color.

[0210] In a separate container is added the maltitol, cyclodextrin, isomalt, maltodextrin and mannitol. The three are combined and mixed until homogeneous. This is mix 1. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. In a separate container is added the tadalafil, sodium dodecyl sulfate and sodium citrate. This is mix 2. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin mixture is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free Tadalafil Gummy

[0211] 76.0 grams pectin; 1050.5 grams Maltitol; 840.5 grams Isomalt, 180 grams Maltodextrin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 30.0 grams beta-cyclodextrin; 5.00 grams Tadalafil, 0.5 gram Sodium Dodecyl Sulfate, Acid; Malic Acid; 12 grams CFR Title 21 Granular Pineapple Flavor; 5 grams CFR Title 21 FD&C Yellow Color.

[0212] In a separate container is added the maltitol, cyclodextrin, isomalt, maltodextrin and mannitol. The three are combined and mixed until homogeneous. This is mix 1. Mix 1 is added to a separate container and water is added. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. In a separate container is added the tadalafil, sodium dodecyl sulfate and sodium citrate. This is mix 2. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin mixture is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. 10 mg Tadalafil Gummy

[0213] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; Orange Flavor USP; 1.36 grams Tadalafil; 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); glycerol; Root Beer flavor; 0.6 grams brown caramel color

[0214] In a separate container is added the pectin, 100 grams of sucrose, tadalafil, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, brown color, and root beer flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 79 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example 2. 10 mg Tadalafil Gummy

[0215] 40 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 2.80 grams Tadalafil; 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); glycerol; Bourbon Flavor; brown caramel color

[0216] In a separate container is added the pectin, 100 grams of sucrose, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, cyclodextrin, tadalafil hydrochloride, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 79 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. Sugar Free 10 mg Tadalafil Gummy

[0217] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Maltodextrin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 11.00 grams Tadalafil; Citric Acid; Malic Acid; Pineapple Flavor; Yellow Color.

[0218] In a separate container is added the maltodextrin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. Sugar Free 10 mg Tadalafil Gummy

[0219] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Soluble Corn Fiber, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams cyclodextrin; 11.00 grams Tadalafil; Citric Acid; 4.0 grams Malic Acid; Pineapple Flavor; Yellow Color.

[0220] In a separate container is added the soluble corn fiber, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. Sugar Free 10 mg Tadalafil Gummy

[0221] Water; 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Soluble Tapioca Fiber, grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 11.00 grams Tadalafil; 8 grams Citric Acid; 4.0 grams Malic Acid; 12 grams Pineapple Flavor; 6 grams Yellow Color.

[0222] In a separate container is added the soluble tapioca fiber, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. Sugar Free 10 mg Tadalafil Gummy

[0223] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Inulin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 11.00 grams Tadalafil; Citric Acid; Malic Acid; 2 grams Pineapple Flavor; Yellow Color.

[0224] In a separate container is added the inulin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 3 is added to the water solution of Mix 2 with stirring. Mix 3 is added to the water solution of Mix 2 with stirring. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. Sugar Free 10 mg Tadalafil Gummy

[0225] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; cyclodextrin; 10.00 grams Tadalafil; 4 grams Citric Acid; 4.0 grams Malic Acid; 8 grams Pineapple Flavor; Chili Flavor: Yellow Color.

[0226] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. Sugar Free 10 mg Tadalafil Gummy

[0227] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams cyclodextrin; 10.00 grams Tadalafil; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0228] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 5 mg Tadalafil Gummy

[0229] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams -cyclodextrin; 5.00 grams Tadalafil; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0230] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 5 mg Tadalafil Gummy

[0231] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Maltodextrin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 5.50 grams Tadalafil; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0232] In a separate container is added the maltodextrin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 5 mg Tadalafil Gummy

[0233] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Inulin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams cyclodextrin; 5.50 grams Tadalafil; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0234] In a separate container is added the inulin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 10 mg Tadalafil Gummy with Zinc

[0235] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Soluble Tapioca Fiber, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams cyclodextrin; 11.00 grams Tadalafil; 2.10 grams Zinc Sulfate, 8 grams Citric Acid; 4.0 grams Malic Acid; 12 grams Pineapple Flavor; Yellow Color.

[0236] In a separate container is added the soluble tapioca fiber, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sodium citrate, zinc sulfate and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. Sugar Free 10 mg Tadalafil Gummy with Zinc

[0237] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Inulin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams beta-cyclodextrin; 11.00 grams Tadalafil; 2.10 grams Zinc Sulfate, 8 grams Citric Acid; 4.0 grams Malic Acid; 12 grams Pineapple Flavor; 6 grams Yellow Color.

[0238] In a separate container is added the inulin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sodium citrate, zinc sulfate and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. 10 mg Tadalafil Gummy with Zinc

[0239] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 2.80 grams Tadalafil; 0.400 grams zinc sulfate, 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 4.5 grams Bourbon Flavor; 0.6 grams brown caramel color

[0240] In a separate container is added the pectin, sucrose, cyclodextrin, zinc sulfate and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, cyclodextrin, tadalafil hydrochloride, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 83 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. Sugar Free 10 mg Tadalafil Gummy with Vardenafil

[0241] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Inulin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 11.00 grams Tadalafil; 1.10 grams Vardenafil Hydrochloride, 8 grams Citric Acid; 4.0 grams Malic Acid; 12 grams Pineapple Flavor; 6 grams Yellow Color.

[0242] In a separate container is added the inulin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, vardenafil hydrochloride, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example 16. Sugar Free 10 mg Tadalafil Gummy with Vardenafil

[0243] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams -cyclodextrin; 11.00 grams Tadalafil; 1.10 grams Vardenafil Hydrochloride, 8 grams Citric Acid; 4.0 grams Malic Acid; 12 grams Pineapple Flavor; 6 grams Yellow Color.

[0244] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, vardenafil hydrochloride, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. 10 mg Tadalafil Gummy with Vardenafil

[0245] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 2.80 grams Tadalafil; 0.200 grams vardenafil hydrochloride, 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 4.5 grams Bourbon Flavor; 0.6 grams brown caramel color

[0246] In a separate container is added the pectin, 100 grams of sucrose, cyclodextrin, zinc sulfate and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, cyclodextrin, tadalafil, vardenafil hydrochloride, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 83 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. Sugar Free 10 mg Tadalafil Gummy with Sildenafil

[0247] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Inulin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams O-cyclodextrin; 11.00 grams Tadalafil; 1.10 grams Sildenafil Citrate, 8 grams Citric Acid; 4.0 grams Malic Acid; 12 grams Pineapple Flavor; 6 grams Yellow Color.

[0248] In a separate container is added the inulin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sildenafil citrate, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. 10 mg Tadalafil Gummy with Sildenafil

[0249] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams gamma-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 2.80 grams Tadalafil; 0.200 grams sildenafil citrate, 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 4.5 grams Bourbon Flavor; 0.6 grams brown caramel color.

[0250] In a separate container is added the pectin, 100 grams of sucrose, cyclodextrin, zinc sulfate and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, cyclodextrin, tadalafil, sildenafil citrate, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 83 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. Sugar Free 10 mg Tadalafil Gummy with Flibanserin

[0251] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Inulin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 11.00 grams Tadalafil; 1.10 grams Flibanserin, 8 grams Citric Acid; 4.0 grams Malic Acid; 12 grams Pineapple Flavor; 6 grams Yellow Color.

[0252] In a separate container is added the inulin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, flibanserin, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. 10 mg Tadalafil Gummy with Flibanserin

[0253] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 2.80 grams Tadalafil; 0.200 grams Flibanserin, 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 4.5 grams Bourbon Flavor; 0.6 grams brown caramel color.

[0254] In a separate container is added the pectin, 100 grams of sucrose, cyclodextrin, and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, cyclodextrin, tadalafil, flibanserin, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 83 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. Sugar Free 10 mg Tadalafil Gummy with Mirodenafil

[0255] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 200 grams Inulin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 11.00 grams Tadalafil; 1.10 grams Mirodenafil, 8 grams Citric Acid; 4.0 grams Malic Acid; 12 grams Pineapple Flavor; 6 grams Yellow Color.

[0256] In a separate container is added the inulin, maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, mirodenafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 83 at which time the flavor and color are added. The syrup is then added to molds to yield gummies that were 3200 mg is mass.

Example. 10 mg Tadalafil Gummy with Mirodenafil

[0257] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 2.80 grams Tadalafil; 0.200 grams Mirodenafil, 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 4.5 grams Bourbon Flavor; 0.6 grams brown caramel color.

[0258] In a separate container is added the pectin, 100 grams of sucrose, cyclodextrin, and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, cyclodextrin, tadalafil, mirodenafil, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 83 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. Sugar Free 10 mg Tadalafil Gummy

[0259] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 10.00 grams Tadalafil; 1.0 gram Sodium dodecyl sulfate, 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0260] In a separate container is added the maltitol, cyclodextrin, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil and sodium citrate. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. and the sodium dodecyl sulfate added. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 10 mg Tadalafil Gummy

[0261] 75.0 grams pectin; 1050.5 grams Maltitol; 840.5 grams Isomalt, 180 grams Maltodextrin, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 10.00 grams Tadalafil; 1.0 gram Sodium dodecyl sulfate, 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; CFR Title 21 beta-Carotene Orange Color.

[0262] In a separate container is added the maltitol, cyclodextrin, isomalt, maltodextrin and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil and sodium citrate. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. and the sodium dodecyl sulfate added. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup.

Example. Sugar Free 10 mg Tadalafil Gummy

[0263] 75.0 grams pectin; 1120.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 20 grams N-Acetylglucosamine, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 10.00 grams Tadalafil; 1.0 gram Sodium dodecyl sulfate, 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0264] In a separate container is added the maltitol, N-acetylglucosamine, cyclodextrin, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil and sodium citrate. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. and the sodium dodecyl sulfate added. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 10 mg Tadalafil Gummy

[0265] 78 g pectin; 1030.5 grams Maltitol; 840.5 grams Isomalt, 180 grams Maltodextrin, 30.0 grams Mannitol, grams N-Acetylglucosamine, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 10.00 grams Tadalafil; 1.0 gram Sodium dodecyl sulfate, 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0266] In a separate container is added the maltitol, maltodextrin, N-acetylglucosamine, cyclodextrin, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil and sodium citrate. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. water is added to a container and heated to 99 C. and the sodium dodecyl sulfate added. Mix 2 is added to the water with stirring. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds. Mix 3 is added to the water solution of Mix 2 with stirring. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 10 mg Tadalafil Gummy

[0267] 74 pectin; 1140.5 grams Sorbitol; 930.5 grams Xylitol, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 10.00 grams Tadalafil; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0268] In a separate container is added the sorbitol, xylitol and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil, sodium citrate, and cyclodextrin. This is mix 2. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 10 mg Tadalafil Gummy

[0269] 72 g pectin; 1120.5 grams Sorbitol; 930.5 grams Xylitol, 30.0 grams Mannitol, 20 grams N-Acetylglucosamine, 3.0 grams Sodium Citrate; 35.0 grams -cyclodextrin; 10.00 grams Tadalafil; 1.0 gram Sodium dodecyl sulfate, 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0270] In a separate container is added the maltitol, N-acetylglucosamine, cyclodextrin, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil and sodium citrate. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. and the sodium dodecyl sulfate added. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds. Mix 3 is added to the water solution of Mix 2 with stirring. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. Sugar Free 10 mg Tadalafil Gummy

[0271] 75.0 grams pectin; 1140.5 grams Sorbitol; 930.5 grams Xylitol, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 10.00 grams Tadalafil; 1.0 gram Sodium dodecyl sulfate, 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0272] In a separate container is added the maltitol, N-acetylglucosamine, cyclodextrin, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the tadalafil and sodium citrate. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. and the sodium dodecyl sulfate added. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is heated to Brix 83 and then added to molds.

Example. 10 mg Tadalafil Gummy

[0273] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Glucose Syrup; 2.8 grams Tadalafil; 0.3 grams Sodium dodecyl sulfate, 10 Grams Citric Acid; 4.5 grams Bourbon Flavor; 0.6 grams brown caramel color

[0274] In a separate container is added the pectin, 100 grams of sucrose, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, cyclodextrin, tadalafil hydrochloride, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan and sodium dodecyl sulfate is added. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 83 at which time Mix 3 was added dropwise with stirring. The gummy syrup was then added to silicone molds.

Example. 10 mg Tadalafil Gummy

[0275] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 120 Grams Sucrose; 10 grams N-acetylglucosamine, 100 grams Fructose; 15.0 grams beta-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Glucose Syrup; 2.80 grams Tadalafil; 10 Grams Citric Acid; 4.5 grams Root Beer Flavor; 0.6 grams brown caramel color. [what is N-acetylglucosamine for/]

[0276] In a separate container is added the pectin, 100 grams of sucrose, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, N-acetylglucosamine, and mannitol. The components are mixed until homogeneous. This is mix 2. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. In a separate container is added the citric acid solution, cyclodextrin, tadalafil hydrochloride, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan and sodium dodecyl sulfate is added. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. The mixture was heated to Brix 83 at which time Mix 3 was added dropwise with stirring. The gummy syrup was then added to silicone molds.

Example. 10 mg Tadalafil Gummy

[0277] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 120 Grams Sucrose; 10 grams N-acetylglucosamine, 100 grams Fructose; 0.3 grams Sodium dodecyl sulfate, 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Glucose Syrup; 2.80 grams Tadalafil; 10 Grams Citric Acid; 4.5 grams Root Beer Flavor; 0.6 grams brown caramel color

[0278] In a separate container is added the pectin, sucrose, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cyclodextrin, fructose, N-acetylglucosamine, and mannitol. The components are mixed until homogeneous. This is mix 2. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. In a separate container is added the citric acid solution, cyclodextrin, tadalafil hydrochloride, brown color, and bourbon flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan and sodium dodecyl sulfate is added. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells. The solution is brought to a boil. The mixture was heated to Brix 83 at which time Mix 3 was added dropwise with stirring. The gummy syrup was then added to silicone molds.

Example. Sugar Free 30 mg Sildenafil Gummy

[0279] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 50.0 grams -cyclodextrin; 31.50 grams Sildenafil Citrate; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0280] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the sildenafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is then heated to Brix 83 and then added to molds.

Example. Sugar Free 25 mg Mirodenafil Gummy

[0281] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 50.0 grams -cyclodextrin; 25.4 grams Mirodenafil; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0282] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the mirodenafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is then heated to Brix 83 and then added to molds.

Example. Sugar Free 25 mg Fibanserin Gummy

[0283] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 50.0 grams -cyclodextrin; 25.4 grams Flibanserin; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0284] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the flibanserin, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is then heated to Brix 83 and then added to molds.

Example. 2 mg Vardenafil Gummy

[0285] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams alpha-cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 1.51 grams vardenafil hydrochloride; 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 4.5 grams Root Beer flavor; 0.6 grams brown caramel color

[0286] In a separate container is added the pectin, 100 grams of sucrose, vardenafil hydrochloride, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, brown color, and root beer flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 79 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. Sugar Free 20 mg Vardenafil Gummy

[0287] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams gamma-cyclodextrin; 20.20 grams Vardenafil Hydrochloride; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0288] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the vardenafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is then heated to Brix 83 and then added to molds.

Example. Sugar Free 10 mg Vardenafil Gummy

[0289] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams -cyclodextrin; 10.0 grams Vardenafil Hydrochloride; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Raspberry Flavor; 6 grams CFR Title 21 Watermelon Red Color.

[0290] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the vardenafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and 400 grams of water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is then heated to Brix 83 and then added to molds.

Example. 8 mg Sildenafil Gummy

[0291] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 15.0 grams -cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 7.65 grams sildenafil citrate; 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 4.5 grams Raspberry flavor; 0.6 grams Red color

[0292] In a separate container is added the pectin, 100 grams of sucrose, sildenafil citrate, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, red color, and raspberry flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 79 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. 8 mg Sildenafil Chocolate Gummy

[0293] 285.0 grams Water; 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 30 grams Cacao Powder, 15.0 grams -cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 8.10 grams sildenafil citrate; 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 1.2 grams Raspberry flavor

[0294] In a separate container is added the pectin, 100 grams of sucrose, sildenafil citrate, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, cacao powder, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, and raspberry flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 79 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. 30 mg Sildenafil Gummy

[0295] 40.3 grams pectin; 100.0 grams Sucrose; 3.0 grams Sodium Citrate; 130 Grams Sucrose; 100 grams Fructose; 30.0 grams -cyclodextrin; 20.0 grams Mannitol; 410.0 grams Boling Glucose Syrup; 31.5 grams sildenafil citrate; 20.0 grams 50% Citric Acid solution (in 50% glycerol/water); 5.0 grams glycerol; 4.5 grams Raspberry flavor; 0.6 grams Red color

[0296] In a separate container is added the pectin, 100 grams of sucrose, sildenafil citrate, cyclodextrin and the sodium citrate. The components are mixed until homogeneous. This is mix 1. In a separate container is added the remaining sucrose, fructose, and mannitol. The components are mixed until homogeneous. This is mix 2. In a separate container is added the citric acid solution, red color, and raspberry flavor. All is mixed and warmed to 175 F. until all is dissolved. This is Mix 3. Water is heated to 200 F. in a saucepan. To the hot water is added Mix 1. The mixture is stirred until the pectin fully swells and disperses which takes roughly 3-5 minutes. The solution is brought to a boil. Mix 2 is added to the boiling glucose syrup is then added to the boiling pectin/sugars/oil mix. The mixture was heated to Brix 79 at which time Mix 3 was added dropwise with stirring. The molding mixture was then added to silicone molds.

Example. Sugar Free 10 mg Sildenafil Gummy

[0297] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams beta-cyclodextrin; 10.0 grams Sildenafil Citrate; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0298] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the sildenafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is then heated to Brix 83 and then added to molds.

Example. Sugar Free 20 mg Sildenafil Gummy

[0299] 75.0 grams pectin; 1140.5 grams Maltitol; 930.5 grams Isomalt, 30.0 grams Mannitol, 3.0 grams Sodium Citrate; 35.0 grams alpha-cyclodextrin; 20.20 grams Sildenafil Citrate; 4 grams Citric Acid; 4.0 grams Malic Acid; 12 grams CFR Title 21 Granular Orange Flavor; 6 grams CFR Title 21 beta-Carotene Orange Color.

[0300] In a separate container is added the maltitol, isomalt and mannitol. The three are combined and mixed until homogeneous. This is mix 1. In a separate container is added the sildenafil, sodium citrate, and cyclodextrin. This is mix 2. In a separate container is added the pectin. 300 grams from mix 1 is added to the pectin and mixed until homogeneous. This is Mix 3. Water is added to a container and heated to 99 C. Mix 2 is added to the water with stirring. This solution is allowed to stir for the 30 minutes. Mix 1 is added to a separate container and water is added. The container temperature is set to 270 F. The mixture is heated and begins to boil to create a hot syrup solution. The malic and citric acids are added to the syrup. Mix 3 is added to the water solution of Mix 2 with stirring. The solution is allowed to stir for 5-10 minutes. The pectin container is then added to the hot syrup. The mixture is allowed to heat until Brix 82 at which time the flavor and color are added. The solution is then heated to Brix 83 and then added to molds.