A NON-SWALLOWED, ANTACID CHEWING GUM PRODUCT, A PROCESS FOR ITS PREPARATION AND USES THEREOF

Abstract

The present invention provides a non-swallowed, antacid chewing gum tablet comprising various antacid components with improved organoleptic properties. The invention also provides an extrusion process for obtaining the non-swallowed, antacid chewing gum tablet as well as the use of the extruded chewing gum tablet as an antacid medicament, and for the prevention and/or the treatment of antacid diseases.

Claims

1. A non-swallowed, antacid chewing gum tablet comprising a core and a coating, wherein the tablet comprises calcium carbonate as antacid active ingredient, and, the core comprises: gum base in a percentage between 32.0% and 52.0% w/w of the core, sodium alginate as antacid active ingredient in a percentage between 12.0% and 25.0% w/w of the core, and sodium bicarbonate as antacid active ingredient in a percentage between 4.0% and 9.0% w/w of the core.

2. (canceled)

3. The chewing gum tablet of claim 1, with the proviso that the antacid chewing gum tablet does not include a C.sub.2-C.sub.5 polyol or poly(C.sub.2-C.sub.5 alkylene glycol).

4. The chewing gum tablet of claim 1, wherein the sodium alginate is in a percentage between 13.0% and 18.0% % w/w of the core with the proviso that the antacid chewing gum tablet does not include a C.sub.2-C.sub.5 polyol or poly(C.sub.2-C.sub.5 alkylene glycol).

5. The chewing gum tablet of claim 1, wherein the calcium carbonate of the tablet is in the coating.

6. The chewing gum tablet of claim 1, wherein the gum base:sodium alginate % w/w ratio is between 2.3:1 and 3.5:1.

7. The chewing gum tablet of claim 1, wherein the gum base:sodium alginate % w/w ratio is between 2.6:1 and 3:1.

8. The chewing gum tablet of claim 1, wherein the sodium bicarbonate is in a percentage between 5.5% and 7.5% w/w of the core.

9. The chewing gum tablet of claim 1, wherein the calcium carbonate is in a percentage between 24.0% and 32.0% % w/w of the coating.

10. The chewing gum tablet of claim 9, wherein the calcium carbonate is in a percentage between 22.0% and 30.0% % w/w of the coating.

11. The chewing gum tablet of claim 1, wherein the gum base is in a percentage between 38.0% and 47.0% % w/w of the core.

12. The chewing gum tablet of claim 1, wherein one single chewing gum tablet comprises sodium alginate between 8.0 and 14.0% w/w of the tablet and sodium bicarbonate between 2.0 and 6.0% w/w of the tablet.

13. The chewing gum tablet of claim 1, wherein one single chewing gum tablet comprises calcium carbonate between 6.0 and 10.0% w/w of the tablet.

14. The chewing gum tablet of claim 1, wherein one single tablet weights from 2,100 to 2,500 mg and includes sodium alginate from 237 to 263 mg, sodium bicarbonate from 100 to 113 mg, and calcium carbonate from 187 to 207 mg.

15. (canceled)

16. The chewing gum tablet of claim 1, wherein the core further comprises at least one sweetener, humectant, bulking agent or flavoring agent, and the coating further comprises at least one of coloring agent, sweetener, flavoring, emulsifier and polishing agent.

17. (canceled)

18. (canceled)

19. (canceled)

20. A non-swallowed, antacid chewing gum tablet of claim 1 obtained by an extrusion method comprising: a) preparing a mixture with the core ingredients; b) extruding the mixture obtained in step a) and forming the cores; c) preparing a coating syrup with the coating ingredients; d) coating the extruded and formed cores of step b) using the coating syrup of step c) to obtain the non-swallowed, antacid chewing gum tablet, wherein the non-swallowed, antacid chewing gum tablet comprises physical stability of the non-ingestible chewing gum after releasing the antacid components, so that it remains chewable.

21. An extrusion process for manufacturing a non-swallowed, antacid chewing gum tablet comprising a core and a coating as defined in claim 1, wherein the tablet comprises calcium carbonate as antacid active ingredient, and wherein the process comprises the steps of: a) preparing a mixture with the core ingredients, the core ingredients comprising gum base, sodium alginate and sodium bicarbonate; b) extruding the mixture obtained in step a) and forming the cores; c) preparing a coating syrup with the coating ingredients; d) coating the extruded and formed cores of step b) using the coating syrup of step c) to obtain the non-swallowed, antacid chewing gum tablet.

22. The process of claim 21, wherein the extruded and formed cores of step b) are standing until getting harden prior to coating of step d).

23. The process of claim 21, wherein the calcium carbonate is present in the coating, and wherein the process comprises the steps of: a) preparing a mixture with the core ingredients including the gum base, the sodium alginate and the sodium bicarbonate, b) extruding the mixture obtained in step a) and forming the cores; c) preparing a coating syrup with the coating ingredients including the calcium carbonate; d) coating the extruded and formed cores of step b) using the coating syrup of step c) to obtain the non-swallowed, antacid chewing gum tablet.

24. The process of claim 21, wherein the preparation of the coating syrup of step c) includes an initial syrup and/or an antacid syrup and a finishing syrup.

25. (canceled)

26. (canceled)

27. A method of preventing and/or treating a disorder or disease selected from the group consisting of acid regurgitation, heartburn, dyspepsia, gastric reflux, oesophagitis and peptic ulceration, the method comprising: orally administering the non-swallowed, antacid chewing gum tablet of claim 1.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0066] FIG. 1. Raft strength (g) of a tablet of the invention and of Gaviscon Forte.

[0067] FIG. 2. Resilience test of the invention and of Gaviscon Forte.

[0068] FIG. 3. Average calcium dissolution (in mg) of the invention by time in minutes.

DETAILED DESCRIPTION OF THE INVENTION

[0069] As used herein, the term chewing gum includes bubble gum and all types of chewing gum. In the present invention, the terms non-swallowed and non-ingestible have been used indistinctly. Therefore, non-swallowable means non-ingestible, or not to be ingested, not even after being chewed or kept in the mouth. The chewing gum of the invention comprises gum base which is meant to be disposed after being chewed, that is, the remaining solid, which is the gum base, is not-swallowed or not-ingested. The other ingredients of the chewing gum, in particular the active ingredients, are to be ingested, as they are released to the gastrointestinal tract during the chewing act.

[0070] The present invention is directed to an antacid chewing gum comprising a core and a coating that fully or partially covers the core. The antacid chewing gum is formulated in the form of a tablet.

[0071] All percentages used herein are weight percentages unless otherwise specified.

Core

[0072] The core comprises sodium alginate, sodium bicarbonate and gum base.

[0073] The weight of the sodium alginate may be about 12% to about 25% of the weight of the core. In a preferable embodiment, the weight of the sodium alginate may be about 13% to about 18% of the weight of the core.

[0074] The weight of the sodium bicarbonate may be about 4% to about 9% of the weight of the core. In a preferable embodiment, the weight of the sodium bicarbonate may be about 5.5% to about 7.5% of the weight of the core.

[0075] The weight of the gum base may be about 32% to about 52% of the weight of the core. In a preferable embodiment, the weight of the gum base may be about 38% to about 47% of the weight of the core.

[0076] The weight of one core can be from 1.2 to 1.9 g. The weight of one core may vary 5%. In a preferable embodiment, the weight of one core is from 1.5 to 1.7 g.

[0077] As stated above, in the most preferred embodiment, the core comprises the aforementioned components, and the calcium carbonate is in the coating. However, the present invention also contemplates the alternative in which the core further comprises the calcium carbonate.

Coating

[0078] In the most preferred embodiment, the calcium carbonate of the tablet is in the coating. In this preferred embodiment, the weight of the calcium carbonate may be about 20% to about 34% of the weight of the coating. In a preferable embodiment, the weight of the calcium carbonate may be about 22% to about 32% of the weight of the coating. In a still preferable embodiment, from about 24% to about 30% of the weight of the coating.

[0079] In a preferred embodiment, the coating fully coats the core. In another embodiment the coating partially coats the core.

Chewing Gum Tablet

[0080] The weight of the core may be about 60% to about 80% of the weight of the chewing gum tablet. In a preferable embodiment, the weight of the core may be about 65% to about 75% of the weight of the chewing gum tablet.

[0081] The weight of the sodium alginate may be about 8% to about 14% of the weight of the chewing gum tablet. In a preferable embodiment, the weight of the sodium alginate may be about 9% to about 12.5% of the weight of the chewing gum tablet.

[0082] The weight of the sodium bicarbonate may be about 2% to about 6% of the weight of the chewing gum tablet. In a preferable embodiment, the weight of the sodium bicarbonate may be about 3.5% to about 5.2% of the weight of the chewing gum tablet.

[0083] The weight of the gum base may be about 25% to about 35% of the weight of the chewing gum tablet. In a preferable embodiment, the weight of the gum base may be about 27% to about 32% of the weight of the chewing gum tablet.

[0084] The weight of the coating may be about 20% to about 40% of the weight of the chewing gum tablet. In a preferable embodiment, the weight of the coating may be about 25% to about 35% of the weight of the chewing gum tablet.

[0085] The weight of the calcium carbonate may be about 6% to about 10% of the weight of the chewing gum tablet. In a preferable embodiment, the weight of the calcium carbonate may be about 7% to about 9% of the weight of the chewing gum tablet. In a still more preferable embodiment, the weight of the calcium carbonate may be about 7.5% to about 8.5% of the weight of the chewing gum tablet.

[0086] The weight of one single chewing gum tablet is from 2.1 to 2.5 g. The weight of one single tablet may vary 6%. In a preferable embodiment, the weight of one single chewing gum tablet is from 2.2 to 2.4 g.

[0087] The one single tablet weights and includes sodium alginate from 237 to 263 mg, sodium bicarbonate from 100 to 113 mg, and calcium carbonate from 180 to 207 mg.

[0088] Various grades of sodium alginate are commercially available that yield aqueous solutions of varying viscosity. Preferable sodium alginate is of low viscosity grade, particularly from 200 to 800 mPa.Math.s. Generally, the viscosity of a 10% weight/volume aqueous solution, when determined on a Brookfield RVT viscometer using spindle number 3 at 20 r.p.m. at 20 C., falls within the range of 200 to 800 mPa.Math.s. Preferable sodium alginate is selected having a viscosity between 300 and 700 mPa.Math.s. See more detailed information in International Journal of Pharmaceutics 294 (2005) 137-147.

[0089] The insoluble gum base generally comprises elastomers, resins, fats and oils, waxes, softeners and inorganic fillers. The elastomers may include polyisobutylene, isobutyiene-isoprene copolymer, styrene butadiene rubber and natural latexes such as chicle. The resins may include polyvinylacetate and terpene resins. Low molecular weight polyvinylacetate is a preferred resin. Fats and oils may include tallow, soybean and cottonseed oils, hydrogenated vegetable oils and cocoa butter. Gum bases typically also contain antioxidants, colors and emulsifiers. The present invention contemplates employing any commercially acceptable gum base.

[0090] It is understood by the skilled person in this field that the core and the coating may also comprise further, optional components.

[0091] Preferably, the core further comprises at least one of sweeteners, humectants, bulking agents and flavoring agents.

[0092] Preferably, the coating further comprises at least one of coloring agents, sweeteners, flavoring agents, emulsifiers and polishing agents.

[0093] The preferable sweeteners are selected from the group consisting of isomalt, isomaltidex, maltitol, acesulfame potassium, aspartame, saccharin, Lycasin (80/55 maltitol syrup) and mixtures thereof.

[0094] In a preferred embodiment, humectants may be selected from glycerin, Lycasin (80/55 maltitol syrup) and mixtures thereof.

[0095] In a preferred embodiment emulsifier is selected from Arabic gum.

Manufacture of the Chewing Gum Tablet

[0096] The extrusion process for manufacturing the non-swallowed, antacid chewing gum tablet of the first aspect of the invention comprises the steps of: [0097] a) preparing a mixture with the core ingredients; [0098] b) extruding the mixture obtained in step a) and forming the cores; [0099] c) preparing a coating syrup with the coating ingredients; [0100] d) coating the extruded and formed cores of step b) using the coating syrup of step c) to obtain the non-swallowed, antacid chewing gum tablet.
Step aPreparing a Mixture with the Core Ingredients.

[0101] The core ingredients are mixed with the gum base in a mixer. Due to the mixing process the temperature increases and favors that all the ingredients are mixed and/or melted together. Preferably, the temperature reached during the process is around 30 C.-55 C.

[0102] For example, the mixing process can be done in a double sigma mixer.

Step bExtruding the Mixture Obtained in Step a) and Forming the Cores.

[0103] The chewing gum mixture obtained in step a) is cut into portions to feed an extruder that will produce a thick sheet of chewing gum that a forming machine will laminate and produce precut cores at the proper thickness that once conditioned will be coated.

[0104] Preferably, the temperature during this step is below 50 C.

[0105] For example, this step is performed in rolling and scoring machines.

[0106] Preferably, the formed cores stand until getting harden before being coated in step d. Preferably they stand at controlled conditions of humidity and temperature. Preferably they stand at controlled conditions of less than 60% of relative humidity (RH). Preferably they stand at controlled conditions of temperature of less than 25 C., more preferably between 14 and 22 C.

Step cPreparing a Coating Syrup with the Coating Ingredients.

[0107] A coating syrup is preferably an antacid coating syrup which contains calcium carbonate.

[0108] Preferably, the calcium carbonate is present in powder form in the antacid syrup. Preferable calcium carbonate has a purity equal or higher than 99%.

[0109] In one embodiment, the antacid coating syrup comprises calcium carbonate, a sweetener agent, water, and a syrup mucilage.

[0110] The syrup mucilage is a thick aqueous solution that can be prepared with for example a gum such as gum Arabic or with a dextrin. The syrup mucilage, in the antacid coating syrup, is used to suspend insoluble substances and to increase viscosity. The syrup mucilage preferably comprises water and a coating agent. In a preferred embodiment the coating agent is an emulsifying agent or a plasticizer agent. In a preferred embodiment the coating agent is Arabic gum or a dextrin. Preferably, the mucilage comprises water and a coating agent in a ratio of about 55:45 and 45:55% w/w, more preferably in a ratio of about 50:50% w/w. In one embodiment, the syrup mucilage is water and Arabic Gum in a ratio of 50:50% w/w.

[0111] The sweetener agent is preferably isomalt.

[0112] In an alternative embodiment it also contains flavour.

[0113] In a preferred embodiment, the coating comprises various coatings or sub-coatings. In a preferable embodiment, three coating or sub-coatings syrups are prepared and used in subsequent coatings for obtaining a first sealing coating, a second antacid coating and a third finishing coating, for polishing and shining appearance. In another embodiment, where calcium carbonate is only present in the core and not in the coating, there is not a second antacid coating.

[0114] In a preferred embodiment, the respective coating syrups for obtaining each of the coatings (or sub-coatings) included in the coating are prepared as follows:

[0115] In one embodiment, the first coating syrup is the sealing coating syrup which is to be applied to cover the hardened cores formed in step b).

[0116] The sealing coating syrup is obtained from a mixture comprising water and a coating agent. In a preferred embodiment the coating agent is an emulsifying agent or a plasticizer agent. In a preferred embodiment the coating agent is Arabic gum or a dextrin. In a preferable embodiment this initial syrup preferably comprises water and a coating agent in a ratio from 75:25 to 65:35% w/w. Preferably, it comprises water and a coating agent in a ratio of about 70:30% w/w. In a preferred embodiment the coating agent is Arabic gum or a dextrin. In a more preferred embodiment, this initial syrup is a mucilage comprising water and Arabic Gum in a ratio of about 70:30% w/w.

[0117] In one embodiment, the sub-coating having the antacid properties is the second coating. The antacid sub-coating is obtained from applying the antacid coating syrup comprising calcium carbonate.

[0118] In one embodiment, a third coating syrup is prepared for a third sub-coating, said coating being a finishing coating for polishing and shining appearance. The finishing coating syrup preferably comprises water, a coloring agent and a syrup mucilage. In a preferred embodiment it also comprises flavouring agents.

[0119] The prepared syrup mucilage for this finishing coating preferably comprises water and a coating agent. In a preferred embodiment the coating agent of the finishing coating is an emulsifying agent or a plasticizer agent. In a preferred embodiment the coating agent is Arabic gum or a dextrin. Preferably, the syrup mucilage comprises water and a coating agent in a ratio of about 55:45 and 45:55% w/w, more preferably in a ratio of about 50:50% w/w. Preferably, the syrup mucilage comprises water and Arabic Gum in a ratio of about 50:50% w/w.

[0120] In one embodiment, all the water content of the syrup coatings is dried during coating process. In other embodiment, less than 1.1% of residual water remains in the final chewing gum tablets.

Step dCoating the Cores of Step b) Using the Coating Syrup of Step c) to Obtain the Non-Swallowed, Antacid Chewing Gum Tablet.

[0121] Once the chewing gum in the cores is hardened, that is, the cores formed in step b) are hardened, they are ready to be coated. This coating operation preferably comprises repeating the following process: i) wetting the cores with the coating syrup prepared in step c); ii) distributing the syrup; and iii) drying.

[0122] In a preferred embodiment the coating operation comprises applying various coatings or sub-coating syrups.

[0123] In a preferred embodiment the coating operation comprises a first step of applying the sealing coating syrup as prepared in step c) for coating the cores. This coating operation comprises repeating the following process: i) wetting the cores with the sealing coating syrup prepared in step c; ii) distributing the syrup; and iii) drying.

[0124] In a preferred embodiment where the tablet comprises calcium carbonate in the coating, the coating operation comprises a step of applying the antacid coating syrup as prepared in step c) covering the dried sealing coating. This embodiment of coating operation comprises repeating the following process: i) wetting the dried cores coated with the sealing coating with the antacid coating syrup prepared in step c; ii) distributing the syrup; and iii) drying.

[0125] In a preferred embodiment the coating operation comprises a further step of applying the finishing coating syrup as prepared in step c), covering the antacid coating. This coating operation comprises repeating the following process: i) wetting the dried cores coated with the antacid coating with the finishing coating syrup prepared in step c; ii) distributing the syrup; and iii) drying. In an alternative embodiment where the tablet comprises calcium carbonate only in the core, the coating operation comprises a further step of applying the finishing coating syrup as prepared in step c), covering the sealing coating.

[0126] In a preferred embodiment, the coating process i) of wetting the cores (uncoated or already coated) is performed by adding the coating syrup to the cores loaded in a coating pan.

[0127] In a preferred embodiment, the coating process ii) of distributing the syrup is performed by leaving the coating pan rotate to distribute the syrup.

[0128] In a preferred embodiment, the coating process iii) of drying is performed by the following preferred process: by adding Isomalt in powder and/or by blowing air, the air preferably at a temperature of about 10 to 30 C. and relative humidity of about 10% to 30%.

[0129] Subsequent manufacturing steps may comprise passing the coated chewing gums through a metal detector, wrapping, packaging, fill bottles, etc.

EXAMPLES

[0130] Hereinafter, the present invention is described in more detail and specifically with reference to the Examples and Figures, which however are not intended to limit the present invention. The chewing gum tablets of the invention are dismissed after being chewed thoroughly, that is, the chewing gum is not swallowed.

Examples

Example 1Core Preparation

[0131] In this embodiment, the core weights 1,600 mg. As the core weight may vary 5%, this embodiment also encompasses this variation by decreasing or increasing this range in each ingredient.

[0132] The core ingredient quantities from table 1 below are added to a double sigma mixer.

TABLE-US-00001 TABLE 1 Core Ingredients % (wt) Amount (mg) Saccharin 0.200 3.2 Glycerin 0.500 8.0 Isomalt 24.769 396.3 Lycasin 80/55 Maltitol syrup 3.500 56.0 Acesulfame 0.100 1.6 Granular Aspartame 0.100 1.6 Gum Base ZEUS-T 42.000 672.0 Sodium Bicarbonate 6.656 106.5 Sodium Alginate 15.625 250.0 Eucamentol liquid 1.550 24.8 Luctadry Eucamentol powder 5.000 80.0 Total 100.000 1,600

[0133] When the mixing process is finalized, the mass is unloaded. The above mass is cut in portions to feed the extruder that produces a thick sheet. The rollers of the subsequent forming machine will provide size and format the cores. The cores are kept in a conditioning room at controlled conditions of humidity (<60% RH) and temperature (14 C.-22 C.) to harden.

Example 2Coating Syrups

[0134] Initial syrup: Example of initial coating mucilage is Gum Arabic:Water, 30:70.

[0135] Antacid syrup: An example of antacid syrup comprises:

TABLE-US-00002 Carbonate syrup % (wt) Water 27.500 Isomalt 34.117 Gum Arabic 1.500 Calcium Carbonate 36.883 Total 100.00

[0136] An example of a finishing syrup comprises:

TABLE-US-00003 Finishing Syrup % (wt) Water 30.550 Isomalt 67.900 Gum Arabic 1.500 Total 100.00

Example 3Coating the Cores

[0137] The term antacid syrup is understood the sub-coating syrup that includes the calcium carbonate as antacid active ingredient of the coating. [0138] The term pellet means a coated core, in which the core is coated by the total amount of the coating or only by a part of the total amount used in the coating. [0139] 1. The coating pan or coater was loaded with the cores of Example 1 when they were hard enough, usually after 2 to 14 days on the conditioning room (T<25 C.; RH<60%). The unit weight is 1.6 g per unit (5%). [0140] 2. The coating operation has 3 phases. The coater is always rotating. [0141] a. The initial syrup (mucilage of Water:Arabic Gum 70:30) of Example 2 was applied over the dried cores by applying layers as follows: [0142] i. Adding the syrup to wet the cores [0143] ii. Leaving the pan rotate to distribute the syrup [0144] iii. Drying adding Isomalt in powder [0145] Therefore obtaining the cores coated with Arabic Gum and Isomalt. [0146] b. The antacid syrup (calcium carbonate syrup) was applied over the dried cores coated with Arabic Gum and Isomalt as follows: [0147] i. Adding the syrup to wet the cores [0148] ii. Letting the coating pan rotate to distribute the syrup [0149] iii. Dry the syrup: [0150] 1. With addition of Isomalt powder in the first 3 syrup applications or [0151] 2. Blowing air at 10 C.-30 C., RH 10%-30% for the following syrup layers. [0152] These steps (i, ii and iii) were repeated until the desired weight of calcium carbonate was reached and: [0153] iv. when the pellets (coated cores) reached around 1.89 g, acesulfame was dissolved in the syrup for one layer application, added to the coating pan to follow steps i, ii and iii. [0154] v. When the pellets (coated cores) reached around 1.92 g, the flavor was added in two applications, dried by isomalt powder, separated by two normal applications. [0155] vi. The coating was continued until the weight of the pellet is around 2.15 g. [0156] c. Finishing [0157] The process was continued with same steps i, ii and iii until the weight is 2.3 g per pellet but using the finishing syrup of Example 2. [0158] 3. Polishing [0159] To the obtained pellets, half of the carnauba wax was added. The coating pan continued rotating for a while. The remaining carnauba wax was finally added to the pellets in the rotating coating pan, obtaining final shining pellets (the antacid chewing gum tablet).

[0160] The unit weight of the final tablet or pellet of the Example is 2.3 g (6%).

Example 4Coating Ingredients

[0161] The table below includes an Example of a final composition of the coating in the manufactured antacid chewing gum of the invention. The coating weights 700 mg although it may vary.

TABLE-US-00004 TABLE 2 Coating ingredients % (wt) Amount (mg) Calcium Carbonate 26.983 188.881 Isomalt 12.396 86.772 Arabic Gum 2.212 15.484 Carnauba Wax 0.329 2.303 Acesulfame 0.036 0.252 Isomaltidex 56.073 392.511 Eucamentol liquid 1.971 13.797 Total 100.00 700.00

[0162] The content of Table 1 that includes the core ingredient quantities and the content of Table 2 that includes the coating ingredient quantities is summarized below together with the weight partial percentage of the core and of the coating as well as the global percentage of the total chewing gum tablet.

TABLE-US-00005 Unitary Partial Global Amount Formula Formula Material (mg) (% p/p) (% p/p) CORE Sodium Alginate (API) 250 15.63 10.87 Sodium Bicarbonate 106.5 6.66 4.63 Base Gum 672 42 29.22 Isomalt 396.3 24.77 17.23 Lycasin 80/55 Maltitol syrup 56 3.5 2.43 Glycerin 8 0.5 0.35 Saccharin 3.2 0.2 0.14 Luctadry Eucamentol powder 80 5 3.48 Eucamentol liquid 24.8 1.55 1.08 Granular Aspartame 1.6 0.1 0.07 Acesulfame 1.6 0.1 0.07 TOTAL CORE 1,600 100 69.6 COATING Calcium Carbonate (API) 187.5 26.79 8.15 Arabig Gum 15.5 2.21 0.67 Isomalt 86.8 12.4 3.77 Canauba Wax 2.3 0.33 0.1 Acesulfame 0.2 0.03 0.01 Isomaltidex 393.9 56.27 17.13 Eucamentol liquid 13.8 1.97 0.6 TOTAL COATING 700 100 30.4 TOTAL CHEWING GUM TABLET 2,300 100

Example 5Comparative Studies with Other Antacid Products

[0163] The following methods are published on International Journal of Pharmaceutics, 2005, 294, 137-147, as well as some of the results of the products in the market. Gaviscon Forte's results were obtained in the laboratory by the inventors as the examples of the invention.

[0164] The speed and character of raft formation of the antacid chewing gum of Example 3 is compared in Table 3.

TABLE-US-00006 TABLE 3 Speed and character of raft formation by product Formation Product speed Flotation Coherence Algicon Immediate Partial Poor Gastrocote Slow Partial Good Gaviscon Advance Immediate Complete Good Gaviscon Liquid Immediate Complete Good Gaviscon Regular Strength (USA) Slow Very low Poor Gaviscon Extra Strength (USA) Slow Very low Poor Mylanta Heartburn Relief Immediate Complete Good Peptac Slow Partial Good Rennie Duo Immediate Complete Good Gaviscon Forte Immediate Complete Good Example 3 (invention) Inmediate Complete Good

[0165] Table 4 below shows the raft strength (g), and raft volume (mL) of the antacid chewing gum of Example 3 as compared with other antacid products in the market. Results obtained for Gaviscon Forte and Example 3 of the invention are shown in FIG. 1.

TABLE-US-00007 TABLE 4 Raft strength (g), and raft volume (mL) Product Raft strength(g) Raft volume (ml) Algicon 1.6 11.2 Gastrocote 7.9 21.1 Gaviscon Advance 16.5 25.8 Gaviscon Liquid 12.9 88.7 Gaviscon Regular Strength (USA) 1.8 5.8 Gaviscon Extra Strength (USA) 1.1 10.4 Mylanta Heartburn Relief 4.6 36.8 Peptac 10.8 42.3 Rennie Duo 4.1 28.0 Gaviscon Forte 15.9 47.0 Example 3 (invention) 18.5 52.8

Example 6Resilience

[0166] Raft strength is also related to raft resilience. The resistance to break-up under the conditions of movement in the raft resilience test is improved with increase in raft strength.

[0167] In Example 5, Table 4, Gaviscon Forte and the chewing gum of Example 3 show high raft strength.

[0168] As shown in FIG. 2, Gaviscon Forte and the chewing gum of Example 3 present high and similar resistance to raft break-up in the resilience test.

Example 7Calcium Dissolution

[0169] The release of Calcium carbonate for the chewing gum of the invention is determined by measure of Calcium by ICP-OES method according to the European Pharmacopoeia (method 2.9.3): Dissolution test for solid oral dosage forms, under the conditions described in section 2.1. The test was performed for six samples (V1-V6). See below Table 5.

TABLE-US-00008 TABLE 5 Time V1 V2 V3 V4 V5 V6 Average SD RSD Max Min 0 min 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.0% 0.00 0.00 5 min 224.37 216.96 149.19 199.76 233.08 204.67 33.35 16.3% 233.08 149.19 10 min 219.94 197.69 198.64 221.74 203.08 211.26 208.72 10.55 5.1% 221.74 197.69 20 min 247.45 192.92 179.80 172.87 197.87 198.18 29.30 14.8% 247.45 172.87 30 min 205.02 173.32 202.23 185.57 226.34 179.34 195.30 19.69 10.1% 226.34 173.32

[0170] FIG. 3 shows the results of the average column.

Example 8Acid Neutralizing Capacity

[0171] The acid-neutralizing capacity (ANC) of an antacid is the amount of acid that can be neutralized and is determined by a back titration method to a set endpoint of pH 3.5.

Solutions Preparations

[0172] Purified water [0173] 0.5N Sodium hydroxide: Around 20 g sodium hydroxide is weighed accurately and transferred into a clean 1000 mL volumetric flask. It is then dissolved and diluted up to the mark with carbon dioxide free water. [0174] 1.0N Hydrochloric acid: take 87 ml of hydrochloric acid 37% and transfer into a 1000 ml volumetric flask. It is then dissolved and diluted up to the mark with carbon dioxide free water.

Sample Preparation

Chewing Gum:

[0175] Weigh one chewing gum and grinded into a fine powder or cut into the minimum pieces possible. [0176] Transfer into a suitable beaker (150-250 ml) and add 70 ml of purified water. [0177] Stir and homogenize the solution for 1 minute. [0178] Add accurately 30 ml of 1.0N hydrochloric acid and stir well during 15 min exactly. [0179] After that the excess hydrochloric acid is titrated immediately with NaOH 0.5N until a stable pH of 3.5 is achieved (during about 10-15 seconds).

Calculations

[00001]$\mathrm{Total}\mathrm{mEq}=\left(30N_{HCl}\right)-\left(V_{\mathrm{NaOH}}{N}_{NaOH}\right)$ [0180] where: [0181] N.sub.HCl=Hydrochloric acid normality [0182] V.sub.NaOH=Volume of NaOH used [0183] N.sub.NaOH=Sodium hydroxide normality

[0184] Results of two tablets are shown below:

TABLE-US-00009 N V N total Weigh (mg) Samples HCl NaOH NaOH mEq 2,282.1 Chewing gum 1 51.9 0.5 4.1 tablet invention 1C-03/21_M1 2,219.6 Chewing gum 1 50.3 0.5 4.9 tablet invention 1C-03/21_M2 Average 4.5

[0185] Results of the acid-neutralizing capacity (ANC) of the chewing gum tablet of the invention are similar to the values of the prior art, but moreover the invention chewing gum tablet is formulated to be chewed without the need to be swallowed in order to reveal with high efficiency the antacid effect.

Example 9Chewing Gum Tablet Containing all the APIs in the Core

[0186] An antacid chewing gum containing all the APIs in the core was manufactured by compression containing the following ingredients:

TABLE-US-00010 TABLE 6 Name of ingredient Quantity/tablet (mg) Active ingredient Sodium alginate 250.00 mg Calcium carbonate 197.38 Sodium hydrogencarbonate 106.50 Excipients Gumbase 915.62 Isomalt 50.08 Acesulfame K 4.50 Saccharin 2.00 Silicium dioxide 12.00 Magnesium stearate 16.00 Peppermint Durarome Flavor 85.00 Peppermint oil Naefco 16.50 Core weight 1655.68 Opadry 49.67 Tablet sum 1705.35

[0187] The following raw material were charged into the High Shear Mixer (HSM): Sodium alginate, calcium carbonate, sodium hydrogen carbonate, isomalt, acesulfame, saccharin, sillicum dioxide and flavors. The ingredients were mixed for 15 minutes at impeller speed of 300 rpm and chopper off.

[0188] The gum base was sieved in Quadro Comil U20 trough a sieve of 1.80 mm (in another example a 1.905 mm sieve was used).

[0189] The sieved gum was charged into the HSM and mixed with the rest of ingredients for 15 minutes at impeller speed of 600 rpm and chopper speed 1500 rpm. More flavor was sprayed and mixed.

[0190] The mixture was sieved and blended with magnesium stearate.

[0191] The mixture was charged in a tableting machine and tablets obtained by compression.

[0192] The tablets were coated in a coating pan with a previously prepared homogeneous solution of Opadry/water 10:90.

[0193] The above antacid gum was manufactured at lab scale and provided good results. However, the scale-up of the manufacturing process in large scale was inviable.

[0194] The inventors consider that the temperatures reached by the compression process in large amounts made the above mixture hard to manipulate at large scale.