Compositions with a rheological modifier to reduce dissolution variability

• US 9,555,113 B2
• Filed: 03/14/2014
• Issued: 01/31/2017
• Est. Priority Date: 03/15/2013
• Status: Expired due to Fees

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Yum, Su Il, Chao, Wendy, Su, Huey-Ching, Fu, Roger, Zamloot, Michael S., Bratin, Karl, Shanker, Ravi M.
• Primary Examiner(s): Soroush, Ali
• Assistant Examiner(s): Alley, Genevieve S
• Application Number:
  US14/214,057
• Publication Number:
  US 20140275147A1
• Time in Patent Office: 1,054 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

The present disclosure provides compositions (e.g., extended release compositions) which exhibit a desirable pharmacokinetic profile of an active agent while providing reduced dissolution sample variability, e.g., in the form of reduced inter-capsule variability and/or a reduction in storage-time dependent change in mean release of the active agent from the composition. Related methods of making and administering the disclosed compositions and formulations are also provided.

Claims

1. A composition comprising:

oxycodone;

sucrose acetate isobutyrate (SAIB), wherein the SAIB is present in the composition in an amount from about 35% by weight to about 45% by weight relative to the total weight of the composition;

triacetin, wherein the triacetin is present in the composition in an amount from about 31% by weight to about 45% by weight relative to the total weight of the composition;

isopropyl myristate (IPM), wherein the IPM is present in the composition in an amount from about 2% by weight to about 10% by weight relative to the total weight of the composition;

cellulose acetate butyrate (CAB), wherein the CAB is present in the composition at about 2% to about 10% by weight relative to the total weight of the composition;

hydroxyethyl cellulose (HEC), wherein the HEC is present in the composition in an amount from about 2% by weight to about 7% by weight relative to the total weight of the composition; and

silicon dioxide, wherein the silicon dioxide is present in the composition in an amount from 2.4% by weight to about 4.0% by weight relative to the total weight of the composition,

wherein the composition is contained within a capsule.

2. The composition of claim 1, wherein the CAB has a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons.

3. The composition of claim 1, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

4. The composition of claim 1, wherein the silicon dioxide is present in the composition in an amount from about 2.5% by weight to about 2.9% by weight relative to the total weight of the composition.

5. The composition of claim 1, wherein the silicon dioxide is present in the composition in an amount from about 2.5% by weight to about 3.5% by weight relative to the total weight of the composition.

6. The composition of claim 1, wherein the silicon dioxide is present in the composition in an amount from about 2.5% by weight to about 3.2% by weight relative to the total weight of the composition.

7. The composition of claim 1, wherein the silicon dioxide is present in the composition in an amount from about 2.5% by weight to about 3.0% by weight relative to the total weight of the composition.

8. The composition of claim 3, wherein the CAB has a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons.

9. The composition of claim 4, wherein the CAB has a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons.

10. The composition of claim 5, wherein the CAB has a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons.

11. The composition of claim 6, wherein the CAB has a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons.

12. The composition of claim 7, wherein the CAB has a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons.

13. The composition of claim 4, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

14. The composition of claim 5, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

15. The composition of claim 6, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

16. The composition of claim 7, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

17. The composition of claim 9, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

18. The composition of claim 10, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

19. The composition of claim 11, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.