Compositions with a rheological modifier to reduce dissolution variability

• US 9,855,333 B2
• Filed: 01/04/2017
• Issued: 01/02/2018
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• 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): Wax, Robert A
• Assistant Examiner(s): TRUONG, QUANGLONG N
• Application Number:
  US15/398,426
• Publication Number:
  US 20170209581A1
• Time in Patent Office: 363 Days
• Field of Search: None
• 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 are also provided.

Claims

1. A method for administering a pharmacologically active agent to a subject, the method comprising:

orally administering to the subject a composition comprising;

a pharmacologically active agent;

a high viscosity liquid carrier material (HVLCM) having a viscosity of at least 5000 cP at 37°

C. that does not crystallize neat at 25°

C. and 1 atmosphere;

a solvent;

a network former;

water; and

a mineral particle, wherein the mineral particle is present in the composition in an amount from 2.4% by weight to about 5.4% by weight relative to the total weight of the composition,

wherein the composition does not comprise more than 2.0% water by weight, based on total weight of the composition.

2. The method of claim 1, wherein the mineral particle comprises silicon dioxide.

3. The method of claim 1, wherein the pharmacologically active agent is selected from opioid, stimulant, and depressant.

4. The method of claim 1, wherein the pharmacologically active agent is an opioid.

5. The method of claim 1, wherein the pharmacologically active agent is selected from oxycodone, oxymorphone, hydrocodone, and hydromorphone, either in free base form or a pharmaceutically acceptable salt form thereof.

6. The method of claim 1, wherein the pharmacologically active agent is oxycodone, and wherein the method comprises treating pain in the subject.

7. The method of claim 1, wherein the HVLCM is sucrose acetate isobutyrate (SAIB).

8. The method of claim 1, wherein the composition comprises about 35% by weight to about 45% by weight of the HVLCM relative to the total weight of the composition.

9. The method of claim 1, wherein the solvent comprises triacetin.

10. The method of claim 1, wherein the composition comprises about 31% by weight to about 45% by weight of the solvent relative to the total weight of the composition.

11. The method of claim 1, wherein the composition further comprises a rheology modifier.

12. The method of claim 11, wherein the rheology modifier is isopropyl myristate (IPM).

13. The method of claim 11, wherein the composition comprises about 2% by weight to about 10% by weight of the rheology modifier relative to the total weight of the composition.

14. The method of claim 1, wherein the network former comprises cellulose acetate butyrate (CAB).

15. The method of claim 14, wherein the CAB has a number average molecular weight ranging from 50,000 Daltons to 100,000 Daltons.

16. The method of claim 14, wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 41%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.5% to about 1.7%.

17. The method of claim 1, wherein the composition further comprises a hydrophilic agent.

18. The method of claim 17, wherein the hydrophilic agent comprises HEC.

19. The method of claim 1, wherein the mineral particle 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.

20. The method of claim 1, wherein the composition is contained within a capsule.

21. The method of claim 1, wherein the composition is contained within a capsule having a water content of less than about 10% by weight.

22. The method of claim 1, wherein the composition is contained within a capsule comprising hydroxypropyl methylcellulose.

23. The method of claim 1, wherein the composition comprises water at from about 1.0 to 2.0% by weight, based on total weight of the composition.

24. The method of claim 1, wherein the composition does not comprise more than 2.0% water by weight, based on total weight of the composition, following storage of the composition for a period of 12 months at 25°

C. and 60% relative humidity.

25. The method of claim 1, wherein the composition comprises water at from about 1.0 to about 2.0% by weight, based on total weight of the composition, following storage of the composition for a period of 12 months at 25°

C. and 60% relative humidity.