SYSTEM FOR UPPER INTESTINAL DELIVERY OF ACTIVE INGREDIENTS

Abstract

A preparation for releasing an active substance, such as iron, in the upper intestine includes an oral dosage form having an external coating, a coating matrix enveloping the oral dosage form, and the active substance embedded in the coating matrix. The active substance disintegrates from the coating matrix within at least one of the stomach, duodenum, upper jejunum, or any combination thereof.

Claims

1. A preparation for releasing iron in the upper intestine, the preparation comprising: an oral dosage form having an external coating; a coating matrix enveloping the oral dosage form; and iron embedded in the coating matrix, wherein the active substance disintegrates from the coating matrix within at least one of the stomach, duodenum, upper jejunum, or any combination thereof.

2. The preparation of claim 1 wherein the coating matrix contains all of the iron present in the preparation.

3. The preparation of claim 1 wherein the coating matrix contains only a portion of the iron present in the preparation.

4. The preparation of claim 1, wherein the oral dosage form comprises a soft gel capsule, a hard shell gel capsule, a caplet, or a tablet.

5. The preparation of claim 1, wherein the coating matrix comprises a matrix formed between the external coating and a polymer soluble in a pH less than about 5.0.

6. The preparation of claim 1, wherein the coating matrix comprises a matrix formed between the external coating and a polymer soluble in a pH less than about 3.0.

7. The preparation of claim 1, wherein the iron comprises at least one of a ferrous salt, a ferrous complex, a ferrous chelate, a ferric salt, a ferric complex, a ferric chelate, or any combination thereof.

8. The preparation of claim 7, wherein the ferrous chelate comprises ferrous bisglycinate, ferrous asparto-glycinate, or any combination thereof.

9. The preparation of claim 1, wherein disintegration of the iron from the coating matrix begins from about 1 minute to about 15 minutes after ingestion.

10. The preparation of claim 1, wherein disintegration of the iron from the coating matrix is from about 40% to about 100% complete 60 minutes after ingestion.

11. The preparation of claim 1, wherein disintegration of the iron from the coating matrix is from about 60% to about 100% complete 60 minutes after ingestion.

12. The preparation of claim 1, wherein disintegration of the iron from the coating matrix is from about 80% to about 100% complete 60 minutes after ingestion.

13. The preparation of claim 1, wherein the coating matrix comprises an iron content, and dissolution of the iron comprises from about 20% to about 100% of the iron content within 30 minutes after ingestion.

14. The preparation of claim 1, wherein dissolution of the iron comprises from about 40% to about 100% of the iron content within 60 minutes after ingestion.

15. The preparation of claim 1, wherein dissolution of the iron comprises from about 60% to about 100% of the iron content within 60 minutes after ingestion.

16. The preparation of claim 1, wherein dissolution of the iron comprises from about 80% to about 100% of the iron content within 60 minutes after ingestion.

17. The preparation of claim 1, further comprising at least one of a fish oil additive, a calcium additive, sodium lauryl sulfate, talc, silicon dioxide, and stearic acid, or any combination thereof.

18. A method of delivering iron to an upper intestinal region of a subject, the method comprising: forming a preparation, wherein the preparation comprises: an oral dosage form having an external coating, a coating matrix enveloping the oral dosage form, and iron embedded in the coating matrix; and administering the preparation to the subject, wherein the iron disintegrates from the coating matrix within the upper intestinal region of the subject.

19. The method of claim 17, wherein the oral dosage form comprises a soft gel capsule, a hard shell gel capsule, a caplet, or a tablet.

20. The method of claim 17, wherein the coating matrix comprises a matrix formed between the external coating and a polymer soluble in a pH less than about 5.0.

21. The method of claim 17, wherein the coating matrix comprises a matrix formed between the external coating and a polymer soluble in a pH less than about 3.0.

Description

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0017] Some example embodiments now will be described more fully hereinafter. Indeed, the examples described herein should not be construed as being limiting as to the scope, applicability, or configuration of the present disclosure. Rather, these example embodiments are provided so that this disclosure will satisfy applicable legal requirements. As used in the specification, and in the appended claims, the singular forms “a”, “an”, “the”, include plural referents unless the context clearly dictates otherwise.

[0018] Certain example embodiments provide preparations, including but not limited to preparation and nutritional supplements, and methods for releasing an active substance, such as iron in various forms, in the upper intestine. For instance, such preparations and methods may provide, for example, an effective manner for efficiently releasing active substances in the body while avoiding the negative effects of cross-linking. As such, for example, these preparations and methods may permit faster release and increased bioavailability of active ingredients in the body.

[0019] In some example embodiments, a preparation for releasing an active substance in the upper intestine is provided. For instance, the preparation provides an effective manner for efficiently releasing active substances in the body while avoiding the negative effects of cross-linking. As such, for example, these preparations and methods may permit faster release and increased bioavailability of active ingredients in the body. In one aspect, the preparation for releasing an active substance in the upper intestine may include an oral dosage form having an external coating, a coating matrix enveloping the oral dosage form, and the active substance embedded in the coating matrix. In such embodiments, for example, the active substance may disintegrate from the coating matrix within at least one of the stomach, duodenum, upper jejunum, or any combination thereof. According to certain exemplary embodiments, for instance, the preparation may further comprise at least one of a fish oil additive, a calcium additive, or any combination thereof.

[0020] The invention exemplified herein contemplates piggy-backing the active ingredient (by way of example, iron) in an external coating that will form a matrix with a polymer selected to be soluble in a pH of less than about 5.0 and, in some cases, less than about 3.0 such that the active ingredient may be absorbed into the human body in the upper intestinal tract when a preparation containing the active ingredient is administered.

[0021] In accordance with certain exemplary embodiments, for example, the oral dosage form may comprise a soft gel capsule, a hard shell gel capsule, a caplet, or a tablet. In some embodiments, for instance, the coating matrix may comprise a matrix formed between the external coating and a polymer soluble in a pH less than 5.0 (e.g., less than 4.5, less than 4.0, less than 3.5, less than 3.0, less than 2.5, less than 2.0, and less than 1.5. In one embodiment, the polymer will be soluble in a pH of less than about 5.0 and in another embodiment, the polymer will be soluble in a pH of less than about 3.0.

[0022] In accordance with certain exemplary embodiments, for example, the active substance may comprise at least one of a nutrient, a mineral, a vitamin, a pharmaceutical ingredient, or any combination thereof. In certain embodiments, for instance, the active substance may comprise a mineral. In some embodiments, for example, the mineral may comprise at least one of an iron, a calcium, a magnesium, a zinc, an iodine, or any combination thereof. In other embodiments, for instance, the mineral may comprise an iron. In further embodiments, for example, the iron may comprise at least one of a ferrous salt, a ferrous complex, a ferrous chelate, a ferric salt, a ferric complex, a ferric chelate, or any combination thereof. In some embodiments, for instance, the iron may comprise a ferrous chelate. In such embodiments, for example, the ferrous chelate comprises ferrous bisglycinate, ferrous asparto-glycinate, or any combination thereof.

[0023] In accordance with certain exemplary embodiments, for instance, disintegration of the active substance from the coating matrix may begin from about 1 minute to about 15 minutes after ingestion. According to certain exemplary embodiments, for example, disintegration of the active substance from the coating matrix may be from about 40% to about 100% complete 60 minutes after ingestion. In some embodiments, for instance, disintegration of the active substance from the coating matrix may be from about 60% to about 100% complete 60 minutes after ingestion. In further embodiments, for example, disintegration of the active substance from the coating matrix may be from about 80% to about 100% complete 60 minutes after ingestion. As such, in certain embodiments, disintegration of the active substance from the coating matrix may be at a percentage 60 minutes after ingestion from at least about any of the following: 40, 45, 50, 55, 60, 65, 70, 75, and 80% and/or at most about 100, 95, 90, 85, and 80% (e.g., about 50-100%, about 70-95%, etc.).

[0024] In accordance with certain exemplary embodiments, for instance, the coating matrix may comprise an active substance content. In such embodiments, for example, dissolution of the active substance may comprise from about 20% to about 100% of the active substance content within 30 minutes after ingestion. As such, in certain embodiments, dissolution of the active substance content within 30 minutes after ingestion may comprise from at least about any of the following: 20, 25, 30, 35, 40, 45, and 50% and/or at most about 100, 95, 90, 85, 80, 75, 70, 65, 60, and 55% (e.g., about 20-85%, 30-100%, etc.).

[0025] In certain embodiments, for instance, dissolution of the active substance may comprise from about 40% to about 100% of the active substance content within 60 minutes after ingestion. In other embodiments, for example, dissolution of the active substance may comprise from about 60% to about 100% of the active substance content within 60 minutes after ingestion. In further embodiments, for instance, dissolution of the active substance may comprise from about 80% to about 100% of the active substance content within 60 minutes after ingestion. As such, in certain embodiments, dissolution of the active substance content within 60 minutes after ingestion may comprise from at least about any of the following: 40, 45, 50, 55, 60, 65, 70, 75, and 80% and/or at most about 100, 95, 90, 85, and 80% (e.g., about 45-90%, about 65-100%, etc.).

[0026] In another aspect, certain exemplary embodiments provide a method of delivering an active substance to an upper intestinal region of a subject. For instance, this method provides an effective manner for efficiently releasing active substances in the body while avoiding the negative effects of cross-linking. As such, for example, these preparations and methods may permit faster release and increased bioavailability of active ingredients in the body. According to certain embodiments, for example, the method may include forming a preparation, and administering the preparation to the subject. In such embodiments, for instance, the preparation may comprise an oral dosage form having an external coating, a coating matrix enveloping the oral dosage form, and an active substance embedded in the coating matrix such that the active substance disintegrates from the coating matrix within the upper intestinal region of the subject. According to certain exemplary embodiments, for example, the preparation may further comprise at least one of a fish oil additive, a calcium additive, or any combination thereof.

[0027] In accordance with certain exemplary embodiments, for example, the oral dosage form may comprise a soft gel capsule, a hard shell gel capsule, a caplet, or a tablet in the forms and with the active ingredients, coatings and polymers described herein. The oral dosage form may be made according to known techniques for creating various pharmaceutical preparations and nutritional supplements. Such techniques may include, but are not limited to, the formation of capsules such as gelcaps by spraying and dipping. In any such processes, the active substances set forth in the present disclosures are embedded in the coatings and are applied to the remaining preparation payload by including the active substances in the coating layers that are being sprayed onto or dipped around the remaining preparation payload or by other techniques that reach the same result.

[0028] One form polymer found to be soluble at a pH of less than 5.0 and useful in the present invention is Eudragit® E PO ReadyMix available from Evonik Industries of Darmstadt, Germany. Eudragit® E PO ReadyMix is a powder blend polymer that may be used as the gelatin capsule external coating of the present invention. The coating can easily be prepared by only adding water and subjecting the mix to either approximately 30 minutes of high-shear mixing or approximately 60 minutes of propeller mixing. Other components, in addition to the active ingredient (such, by example, iron) may be utilized: sodium lauryl sulfate, talc, silicon dioxide, and stearic acid, to name a few exemplary components. Optional ingredients such as color pigments (e.g., iron oxides, aluminum flakes, and natural colors), flavors and fragrances, and others may also be employed to produce the preparation.

[0029] The active ingredient may be added in various proportions (including up to a full effective load) into the polymer coating.

[0030] Once formed, the coating with embedded active ingredient can be applied by a typical spraying process to form the gelatin capsule. Typically, this will be a low-temperature process. The resulting gelatin capsule will be readily absorbable when it reaches the upper intestinal tract and will release its embedded active ingredient.

[0031] The resulting release of iron, or other active, occurs immediately upon contact with the low pH of the stomach. Therefore, the active ingredient becomes capable of being absorbed in the duodenum or upper jejunum.

[0032] Other ingredients that are absorbed distally in jejunum or ileum are much less affected by delays in disintegration and dissolution. There is an additional benefit in multi-ingredient formulations that contain fish oil together other solid ingredients like calcium that typically turn the content of the gelcap into a thick paste from which iron may have greater difficulty being dissolved in upper gastro-intestinal solution because of the amount of time it takes to diffuse out of the paste-like content. Even when a gelcap is sliced open and placed in an in-vitro simulated gastric and intestinal fluid environment, iron may not be found dissolved in solution in a dissolution test performed on both an intact gelcap containing multiple ingredients of a prenatal formulation, even if the gelcap is sliced in three places and held into gastric solution by a sinker device.

[0033] Many modifications and other embodiments will come to mind to one skilled in the art to which this disclosure pertains having the benefit of the teachings presented in the foregoing descriptions. Therefore, it is to be understood that this disclosure is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Moreover, although the foregoing descriptions describe exemplary embodiments in the context of certain exemplary combinations of elements and/or functions, it should be appreciated that different combinations of elements and/or functions may be provided by alternative embodiments without departing from the scope of the appended claims. In this regard, for example, different combinations of elements and/or functions than those explicitly described above are also contemplated as may be set forth in some of the appended claims. In cases where advantages, benefits or solutions to problems are described herein, it should be appreciated that such advantages, benefits and/or solutions may be applicable to some example embodiments, but not necessarily all example embodiments. Thus, any advantages, benefits or solutions described herein should not be thought of as being critical, required or essential to all embodiments or to that which is claimed herein. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.