FORMULATIONS AND METHODS OF MANUFACTURING FORMULATIONS FOR USE IN COLONIC EVACUATION

• US 20150272937A1
• Filed: 07/26/2013
• Published: 10/01/2015
• Est. Priority Date: 07/27/2012
• Status: Active Grant

• Current Assignee: RedHill Biopharma Ltd.
• Original Assignee: RedHill Biopharma Ltd.
• Inventors: Fathi, Reza, McLean, Patrick Laughlin
• Granted Patent: US 10,166,219 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/375 Ascorbic acid, i.e. vitamin C; Salts thereof
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 33/08 Oxides; Hydroxides
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61P 1/10 Laxatives

Abstract

Formulations and methods of manufacturing formulations for use in colonic evacuation are disclosed herein, in an embodiment, a solid dosage formulation includes an intra-granular fraction intermingled with an extra-granular fraction, wherein the intra-granular fraction includes granules comprising at least one osmotic evacuant agent, at least one antacid, and a first pharmaceutically acceptable excipient component, and wherein the extra-granular fraction includes one or more organic acids, a non-metallic lubricating element, and a second pharmaceutically acceptable excipient component.

Claims

1. A method of manufacturing a solid dosage formulation comprising:

(i) wet granulating at least one osmotic evacuant agent, at least one antacid, and a first pharmaceutically acceptable excipient component to form an intra-granular fraction;

(ii) blending the intra-granular fraction obtained from step (i) with elements of an extra-granular fraction comprising one or more organic acids, a non-metallic lubricating element, and a second pharmaceutically acceptable excipient component; and

(iii) compressing the blend obtained from step (ii) into tablets.

2. The method of claim 1 further comprising:

(iv) coating the tablets.

3. The method of claim 1 wherein the intra-granular fraction comprises about 50% of the total weight of the formulation, and wherein the extra-granular fraction comprises about 50% of the total weight of the formulation.

4. The method of claim 1 wherein the first pharmaceutically acceptable excipient component includes at least one of a binder, a diluent, a stabilizing agent, a disintegrant, an anti-foaming agent, or an antiadherent.

5. The method of claim 1 wherein the second pharmaceutically acceptable excipient component includes at least one of a binder, a diluent, a stabilizing agent, a disintegrant, an anti-foaming agent, or an antiadherent.

6. The method of claim 1 wherein the first pharmaceutically acceptable excipient component includes a first amount of a diluent, and the second pharmaceutically acceptable excipient component includes a second amount of the same diluent so that the diluent in the formulation is evenly divided between the intra-granular fraction and the extra-granular fraction.

7. The method of claim 1 wherein the at least one osmotic evacuant agent component of the intra-granular fraction comprises up to 1% of the total weight of the formulation.

8. The method of claim 1 wherein the at least one antacid component of the intra-granular fraction comprises up to 20% of the total weight of the formulation.

9. The method of claim 1 wherein the first pharmaceutically acceptable excipient component comprises up to 30% of the total weight of the formulation.

10. The method of claim 1 wherein the one or more organic acids of the extra-granular fraction comprises up to 40% of the total weight of the formulation.

11. The method of claim 1 wherein the non-metallic lubricating element of the extra-granular fraction comprises up to 3% of the total weight of the formulation.

12. The method of claim 1 wherein the second pharmaceutically acceptable excipient component comprises up to 10% of the total weight of the formulation

13. A solid dosage formulation comprising:

an intra-granular fraction intermingled with an extra-granular fraction,

wherein the intra-granular fraction includes granules comprising at least one osmotic evacuant agent, at least one antacid, and a first pharmaceutically acceptable excipient component, and

wherein the extra-granular fraction includes one or more organic acids, a non-metallic lubricating element, and a second pharmaceutically acceptable excipient component.

14. The formulation of claim 13 wherein the intra-granular fraction comprises about 50% of the total weight of the formulation, and wherein the extra-granular fraction comprises about 50% of the total weight of the formulation.

15. The formulation of claim 13 wherein the at least one osmotic evacuant agent is micronized sodium picosulfate.

16. The formulation of claim 13 wherein the at least one antacid is magnesium oxide.

17. The formulation of claim 13 wherein the at least one organic acid is ascorbic acid.

18. The formulation of claim 13 wherein the non-metallic lubricating agent is a fatty acid ester.

19. The formulation of claim 13 wherein the first pharmaceutically acceptable excipient component includes at least one of a binder, a diluent, a stabilizing agent, a disintegrant, an anti-foaming agent, or an antiadherent.

20. The formulation of claim 13 wherein the second pharmaceutically acceptable excipient component includes at least one of a binder, a diluent, a stabilizing agent, a disintegrant, an anti-foaming agent, or an antiadherent.

21. The formulation of claim 13 wherein the first pharmaceutically acceptable excipient component includes a first amount of a diluent, and the second pharmaceutically acceptable excipient component includes a second amount of the same diluent so that the diluent in the formulation is evenly divided between the intra-granular fraction and the extra-granular fraction.

22. The formulation of claim 21 wherein the diluent is selected from one or a combination of lactose monohydrate, microcrystalline cellulose or sorbitol.

23. The formulation of claim 13 being in the form of a tablet, a capsule, a lozenge, a pill;

or a bilayer tablet, capsule, lozenge or pill.

24. A method of evacuating a colon of a patient comprising:

orally administering to the patient, within a 24-hour time frame, between 25 and 30 tablets with a liquid,

wherein each of the tablets includes an intra-granular fraction intermingled with an extra-granular fraction,

wherein the intra-granular fraction includes granules comprising sodium picosulfate, magnesium oxide, simethicone, and a first pharmaceutically acceptable excipient component,

wherein the extra-granular fraction includes ascorbic acid and a second pharmaceutically acceptable excipient component, and

wherein all the tablets combined yield a total dose of about 30 mg sodium picosulfate, about 7 g of magnesium oxide, about 15 g of ascorbic acid, and about 100 mg of simethicone.