Stabilization of solid drug formulations

• US 6,979,462 B1
• Filed: 10/18/2000
• Issued: 12/27/2005
• Est. Priority Date: 10/03/2000
• Status: Expired due to Fees

• Current Assignee: Sigmapharm, Sun Pharmaceutical Industries, Inc. (Sun Pharmaceutical Industries Limited)
• Original Assignee: Mutual Pharmaceutical Company (Takeda Pharmaceutical Company Limited)
• Inventors: Spireas, Spiridon
• Primary Examiner(s): Dodson, Shelley A.
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US09/690,974
• Time in Patent Office: 1,896 Days
• Field of Search: 424/456, 424/451, 424/452, 514/21
• US Class Current: 424/451
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

Pharmaceutical formulations and dosage forms are provided having improved stability to moisture-induced degradation when compared with conventional dosage forms, especially tablets. The invention features low compression forms of drugs known to be susceptible to moisture-induced degradation together with excipients, preferably in encapsulated forms. In other embodiments, relatively non-volatile oils can be admixed with the drug and/or the excipients to stabilize the formulations toward moisture-induced degradation. Hydrophobic powders are also optionally added to the formulations.

Claims

1. A drug dosage form prepared by compression techniques comprising:

a substantially non-volatile, pharmaceutically acceptable oil, and

a compound susceptible to moisture-induced degradation treated with the substantially non-volatile, pharmaceutically acceptable oil to substantially waterproof the compound susceptible to moisture-induced degradation;

the drug dosage form prepared by;

(a) dispersing the compound susceptible to moisture-induced degradation in the substantially non-volatile, pharmaceutically acceptable oil; and

(b) compacting the compound susceptible to moisture-induced degradation into dosage forms using compression pressures of up to 5,000 psi/g.

2. The drug dosage form of claim 1 wherein the oil is an animal or vegetable oil.

3. The drug dosage form of claim 1 wherein said oil is olive, corn, peanut, nut, soy, rapeseed, cottonseed, vitamin E, fish, or tallow-derived oil.

4. The drug dosage form of claim 1 wherein the oil is a mineral oil or silicone oil.

5. The drug dosage form of claim 1 wherein the compound—

oil admixture is present within a capsule.

6. The drug dosage form of claim 1 wherein the compound—

oil admixture is present within a soft shell capsule.

7. The drug dosage form of claim 1 wherein the compound—

oil admixture is present within a specially sealed hard-shell capsule.

8. The drug dosage form of claim 1 wherein at least some of the compound—

oil admixture is adsorbed on a pharmaceutically acceptable excipient.

9. The drug dosage form of claim 1 wherein the excipient having the compound—

oil admixture adsorbed thereupon is within a capsule.

10. The drug dosage form of claim 1 wherein the excipient having the compound—

oil admixture adsorbed thereupon is within a tablet.

11. A drug dosage form prepared by compression techniques comprising:

a pharmaceutically acceptable excipient admixed with a substantially non-volatile pharmaceutically acceptable oil; and

a compound susceptible to moisture-induced degradation treated with the pharmaceutically acceptable excipient to substantially waterproof the compound susceptible to moisture-induced degradation;

wherein the drug dosage form is prepared by;

(a) dispersing the compound susceptible to moisture-induced degradation in the pharmaceutically acceptable excipient;

(b) compacting the compound susceptible to moisture-induced degradation into dosage forms using compression pressures of up to 5,000 psi/g.

12. The drug dosage form of claim 11 wherein the oil is an animal or vegetable oil.

13. The drug dosage form of claim 11 wherein said oil is olive, corn, peanut, nut, soy, rapeseed, cottonseed, vitamin E, fish, or tallow-derived oil.

14. The drug dosage form of claim 11 wherein the oil is a mineral oil or silicone oil.

15. The drug dosage form of claim 11 wherein the drug and the excipient—

oil admixture are present within a capsule.

16. The drug dosage form of claim 11 wherein the drug and the excipient—

oil admixture are present within a tablet.

17. A drug form prepared by compression techniques comprising:

a compound susceptible to moisture-induced degradation treated with a first pharmaceutically acceptable oil to substantially waterproof the compound susceptible to moisture-induced degradation; and

a pharmaceutically acceptable excipient admixed with a second pharmaceutically acceptable oil to substantially waterproof the pharmaceutically acceptable excipient, wherein the first pharmaceutical acceptable oil is different from the second pharmaceutically acceptable oil;

the drug dosage form prepared by;

(a) dispersing the compound susceptible to moisture-induced degradation in the pharmaceutically acceptable excipient;

(b) compacting the compound susceptible to moisture-induced degradation into dosage forms using compression pressures of up to 5,000 psi/g.

18. The drug dosage form of claim 17 wherein the first pharmaceutically acceptable oil is an animal oil and the second pharmaceutically acceptable oil is a vegetable oil.

19. The drug dosage form of claim 17 wherein the first and the second pharmaceutically acceptable oils are, independently, olive, corn, peanut, nut, soy, rapeseed, cottonseed, vitamin E, fish, or tallow-derived oil.

20. The drug dosage form of claim 17 wherein the first pharmaceutically acceptable oil is an mineral oil and the second pharmaceutically acceptable oil is a silicone oil.

21. The drug dosage form of claim 17 wherein the compound—

oil admixtured and the excipient—

oil admixture are present within a capsule.

22. The drug dosage form of claim 17 wherein the compound—

oil admixture and the excipient—

oil admixture are present within a tablet.

23. A method for administering a compound susceptible to moisture-induced degradation to a patient comprising providing a unit dose of the compound which has not been processed employing high compression.

24. A method for administering a compound susceptible to moisture-induced degradation to a patient comprising providing a unit dose of the compound admixed with a substantially non-volatile, pharmaceutically acceptable oil.

25. The method of claim 24 wherein the compound—

oil admixture is present within a capsule.

26. The method of claim 24 wherein the compound—

oil admixture is adsorbed on a pharmaceutically acceptable excipient.

27. A method for administering a compound susceptible to moisture-induced degradation to a patient comprising providing a unit dose of the compound and a pharmaceutically acceptable excipient admixed with a substantially non-volatile, pharmaceutically acceptable oil.

28. A method for administering a compound susceptible to moisture-induced degradation to a patient comprising providing a unit dose of the compound and at least one pharmaceutically acceptable hydrophobic powder.