Pharmaceutical compositions with enhanced performance and improved processability

• US 10,106,625 B2
• Filed: 07/22/2016
• Issued: 10/23/2018
• Est. Priority Date: 03/01/2013
• Status: Active Grant

• Current Assignee: Hercules, LLC (Ashland Global Holdings, Inc.)
• Original Assignee: Hercules, LLC (Ashland Global Holdings, Inc.)
• Inventors: Brugel, Todd A., Nguyen, Tuyen T.
• Primary Examiner(s): Jiang, Shaojia A
• Assistant Examiner(s): White, Everett
• Application Number:
  US15/216,936
• Publication Number:
  US 20160376380A1
• Time in Patent Office: 823 Days
• Field of Search: 536 58, 536 69, 536124, 424488
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: C08B 13/00 Preparation of cellulose ether-esters
• CPC Class Codes: C08L 1/32 Cellulose ether-esters

Abstract

The presently disclosed and claimed inventive concept(s) relates to a polymer for enhancing drug performance and improving processability. Specifically, the polymer comprises hydroxypropyl methyl cellulose acetate succinate (HPMC-AS). On the HPMC-AS, the percentage of total succinoyl degree of substitution is less than 12% at C6-OH position and greater than 53% at C3-OH, and the percentage of total acetyl degree of substitution is greater than 32% at C6-OH position.

Claims

1. A method for making hydroxypropyl methyl cellulose acetate succinate (HPMC-AS) comprising the steps of:

(a) reacting an amount of acetic anhydride and sodium acetate with a reaction mixture of hydroxyl propyl methylcellulose and acetic acid at a reaction temperature in a range from about 85 to about 115°

C.;

(b) maintaining the reaction temperature for a time from about 30 minutes to about 2.0 hours to allow reaction and thereby form an intermediate having a percentage of a total degree of substitution (DS) of acetyl greater than 32% at a C6-OH position (% C6DSAc>

32%) of the intermediate; and

(c) reacting the intermediate with an amount of succinic anhydride at the reaction temperature for a time from about 2.5 hours to about 23.5 hours to allow reaction and thereby form HPMC-AS having a percentage of a total DS of succinoyl less than 12% at a C6-OH position (% C6DSSuc<

12%) and greater than 53% at a C3-OH position (% C3DSSuc>

53%).

2. The method of claim 1, wherein the HPMC-AS has a percentage of a total DS of acetyl less than 27% at a C3-OH position (% C3DSAc<

27%).

3. The method of claim 1, wherein the time in step (c) is varied from 2.5 hours to 15.5 hours.

4. The method of claim 3, wherein the time in step (c) is varied from 2.5 hours to 5.5 hours.

5. The method of claim 1, wherein the temperature is in a range from 95 to 115°

C.

6. The method of claim 1, wherein the temperature is in a range from 95 to 110°

C.