Sustained release drug delivery system and method

• US 20060099254A1
• Filed: 11/02/2005
• Published: 05/11/2006
• Est. Priority Date: 11/02/2004
• Status: Abandoned Application

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Desai, Divyakant S., Kothari, Sanjeev H., Sharma, Laxmikant H.
• Application Number:
  US11/266,516
• Publication Number:
  US 20060099254A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/175 having the group , >N—C(O)—N=N— or , e.g. carbonohydrazides, carbazones, semicarbazides, semicarbazones; Thioanalogues thereof
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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 9/4866 Organic macromolecular compounds

Abstract

The present invention relates to a pharmaceutical delivery system comprising a gel-like structure that comprises at least one water-soluble polymer, such as, for example, povidone or hydroxypropyl cellulose, and at least one fatty acid, such as, for example, stearic acid or lauric acid. The invention further relates to a sustained release drug delivery composition comprising the gel-like structure and at least one drug trapped or dissolved therein, wherein said system is capable of releasing the drug in a dissolution medium at a controlled rate. The invention is also directed to a method for preparing the sustained release drug delivery composition.

Claims

1. A pharmaceutical delivery composition in the form of a gel-like structure comprising:

a) a water-soluble polymer; and

b) a fatty acid,

whereby said composition delivers a drug in a sustained release manner.

2. The composition as defined in claim 1, wherein the water-soluble polymer and the fatty acid form a solid solution.

3. The composition as defined in claim 2, wherein the solid solution is formed by mixing the water-soluble polymer and the fatty acid together, and then exposing the mixture to a temperature ranging from about 30 to about 60°

C.

4. The composition as defined in claim 1, wherein the water soluble polymer and the fatty acid each separately have an average particle size of from about 20 to about 100 microns.

5. The composition as defined in claim 1, wherein the water-soluble polymer and the fatty acid are present in a weight ratio of water-soluble polymer to fatty acid ranging from about 2.5:

1 to about 1;

2.

6. The composition as defined in claim 1, wherein the water-soluble polymer is povidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, or polyethylene glycol.

7. The composition as defined in claim 1, wherein the fatty acid is stearic acid, palmitic acid, or lauric acid.

8. The composition as defined in claim 1, wherein the water-soluble polymer is povidone or hydroxypropyl cellulose, the fatty acid is stearic acid or lauric acid, and the water-soluble polymer and the fatty acid are present in a weight ratio of water-soluble polymer to fatty acid of about 1:

1.

9. A sustained release drug delivery composition comprising:

a) at least one drug; and

b) a gel-like structure comprising;

1) at least one water-soluble polymer; and

2) at least one fatty acid,

wherein the drug is trapped or dissolved in the gel-like structure, and the drug is released from the gel-like structure into a dissolution medium at a sustained release rate.

10. The composition as defined in claim 9, wherein the water-soluble polymer and the fatty acid form a solid solution and said drug is trapped in said solid solution.

11. The composition of claim 9, wherein the water-soluble polymer, the fatty acid, and the drug form a solid solution.

12. The composition as defined in claim 10, where said solid solution is formed by exposing the mixture to a temperature ranging from at least about 30°

C. to about 60°

C.

13. The composition as defined in claim 9, wherein the water-soluble polymer and the fatty acid are present in a water-soluble polymer to fatty acid weight ratio ranging from about 2.5:

1 to about 1;

2.

15. The composition as defined in claim 9, wherein the water-soluble polymer is povidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, or polyethylene glycol.

16. The composition as defined in claim 9, wherein the fatty acid is stearic acid, palmitic acid, or lauric acid.

17. The composition as defined in claim 9, wherein the water-soluble polymer is povidone or hydroxypropyl cellulose, the fatty acid is stearic acid or lauric acid, and the water-soluble polymer and the fatty acid are present in a weight ratio of water-soluble polymer to fatty acid of about 1:

1.

18. The composition as defined in claim 9, wherein said composition is in a form selected from a capsule and a lozenge.

19. The composition as defined in claim 9, wherein the drug is a pharmacologically active substance.

20. The composition as defined in claim 19, wherein the pharmacologically active substance is theophylline, acetaminophen, or glipizide.

21. The composition as defined in claim 9, wherein the composition comprises from about 20 to about 50%, by weight composition, of the at least one water-soluble polymer;

from about 20 to about 50%, by weight composition, of the at least one fatty acid; and

from about 3 to about 60%, by weight composition, of the at least one drug.

22. A method for preparing the sustained release drug delivery composition of claim 9, comprising:

a) mixing the drug, the water-soluble polymer, and the fatty acid together;

and

b) heating the mixture of a) at a sufficiently high temperature to melt the fatty acid, wherein said water-soluble polymer and said fatty acid form a solid solution and said drug is trapped or dissolved in said solid solution

23. The method as defined in claim 22, further comprising separately screening each of the drug, the water-soluble polymer, and the fatty acid prior to mixing said drug, said water-soluble polymer, and said fatty acid together in step a), wherein said screening results in each of the drug, the water-soluble polymer, and the fatty acid having an average particle size of from about 20 to about 100 microns.

24. The method as defined in claim 22, wherein the temperature at which the mixture of a) is heated in b) ranges from about 30 to about 60°

C., said mixture being heated in b) for a period of time ranging from about 0.25 to about 10 hours.

25. The method as defined in claim 23, further comprising loading a capsule with the mixture of a), and then subsequently heating the loaded capsule in accordance with step b).

26. The method as defined in claim 23, further comprising transferring the mixture of a) to a lozenge mold, and then subsequently heating said mixture in accordance with step b).

27. A method for preparing the sustained release drug delivery composition of claim 9, comprising:

a) screening each of the at least one drug, the at least one water-soluble polymer, and the at least one fatty acid so that said drug, said water-soluble polymer, and said fatty acid each have an average particle size of from about 20 to about 100 microns;

b) mixing the drug, the water-soluble polymer, and the fatty acid together;

c) transferring the mixture of b) to a capsule or a lozenge mold; and

d) heating the mixture of c) to a temperature ranging from about 35 to about 55°

C. for a period of time ranging from about 0.25 to about 10 hours.

14. The composition as defined in Claim9, wherein the water-soluble polymer, the fatty acid, and the drug have an average particle size of from about 20 to about 100 microns.