Compositions with a rheological modifier to reduce dissolution variability

• US 9,907,851 B2
• Filed: 12/15/2016
• Issued: 03/06/2018
• 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): Richter, Johann R
• Assistant Examiner(s): Alley, Genevieve S
• Application Number:
  US15/380,828
• Publication Number:
  US 20170196978A1
• Time in Patent Office: 446 Days
• 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 method for treating pain in a subject, the method comprising:

orally administering to the subject 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 formulated for oral administration, and one or more symptoms or signs associated with the subject'"'"'s pain is alleviated.

2. The method of claim 1, wherein the composition comprises about 38% by weight to about 41% by weight of the triacetin relative to the total weight of the composition.

3. The method of claim 1, wherein the composition comprises about 2% by weight to about 3% by weight of the IPM relative to the total weight of the composition.

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

5. The method 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%.

6. The method 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 method 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 method 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.

9. The method of claim 1, wherein:

the composition comprises about 38% by weight to about 41% by weight of the triacetin relative to the total weight of the composition,

the composition comprises about 2% by weight to about 3% by weight of the IPM relative to the total weight of the composition,

the CAB has a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons,

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%, and

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.

10. The method of claim 1, wherein the composition is administered no more than twice in a 24-hour period.

11. The method of claim 1, wherein the subject is a human.