Sustained release matrix system using hydroxyethyl cellulose and hydroxypropyl cellulose polymer blends

• US 5,451,409 A
• Filed: 11/22/1993
• Issued: 09/19/1995
• Est. Priority Date: 11/22/1993
• Status: Expired due to Term

• Current Assignee: Ethicon Incorporated (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Babu, Suresh, Musunuri, Shankar, Schwing, James, Rencher, William F., Day, Christopher H.
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US08/156,223
• Time in Patent Office: 666 Days
• Field of Search: 424/468, 424/469, 424/480, 424/484, 424/488, 424/494, 514/963, 514/964, 514/965
• US Class Current: 424/468
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer

Abstract

The present invention is directed to a novel sustained release matrix and oral dosage form comprising a homogeneous matrix formed from a wet granulation containing an effective amount of a medicament and a polymer blend of hydroxypropyl cellulose and hydroxyethyl cellulose. The present invention also discloses a novel process for making a sustained release oral dosage form comprising wet granulating a medicament with a polymer blend of hydroxypropyl cellulose and hydroxyethyl cellulose to form a homogeneous matrix, wherein the polymer blend is provided in an amount effective to control the release of said medicament, then forming the homogenous matrix into a solid oral dosage form.

Claims

1. A sustained release pharmaceutical matrix comprising a homogeneous matrix containing a therapeutically effective amount of a medicament and a polymer blend of hdyroxypropyl cellulose (HPC) and hydroxyethyl cellulose (HEC) provided in an amount of about 18 weight percent or less to provide a sustained release of said medicament, wherein the ratio of HPC to HEC is in the range from about 10:

90 to about 90;

10.

5. The matrix of claim 1 wherein the medicament is selected from the group consisting of antacids, anti-inflammatory drugs, vasodilators, anti-infectives, psychotropics, antimanics, stimulants, antihistamines, laxatives, decongestants, vitamins, gastrointestinal sedatives, antidiarrheal preparations, antianginal drugs, antiarrhythmics, antihypertensive drugs, vasoconstrictor drugs, analgesics, anti-pyretics, hypnotics, sedatives, antiemetics, anti-nauseants, anticonvulsants, neuromuscular drugs, hyperglycemic agents, hypoglycemic agents, thyroid preparations, antithyroid preparations, diuretics, antispasmodics, uterine relaxants, mineral additives, anti-obesity drugs, anabolic drugs, erythropoietic drugs, antiasthmatics, expectorants, cough suppressants, mucolytics, antiuricemic drugs, and combinations of two or more thereof.

6. The matrix of claim 1 wherein the medicament is an NSAID and one or more medicaments selected from the group consisting of decongestants, bronchodilators, antitussives, non-sedating antihistamines, muscle relaxants, adjuvants and combinations of any of the aforesaid medicaments.

8. The matrix of claim 1 wherein the matrix comprises in the range of from about 3 to about 8 weight percent HPC;

in the range of from about 4 to about 8 weight percent HEC;

in the range of from about 20 to about 88 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent terfenadine;

in the range of from about 0.5 to about 5 weight percent of a disintegrant;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.

9. The matrix of claim 1 wherein the matrix comprises in the range of from about 5 to about 10 weight percent HPC;

in the range of from about 1 to about 4 weight percent HEC;

in the range of from about 20 to about 90 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent pseudoephedrine hydrochloride;

in the range of from about 0.5 to about 5 weight percent of a disintegrant;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.

2. The matrix of claim 2 wherein the polymer blend contains in the range of from 80 to 62.5 weight percent HPC and in the range of from 20 to 37.5 weight percent HEC.

3. The matrix of claim 2 wherein the polymer blend contains in the range of from 62.4 to 37.6 weight percent HPC and in the range of from 37.6 to 62.4 weight percent HEC.

4. The matrix of claim 2 wherein the polymer blend contains the range of from 62.5 to 75 weight percent HEC and in the range of from 37.5 to 25 weight percent HPC.

7. The matrix of claim 2 wherein the matrix comprises in the range of from about 5 to about 12 weight percent HPC;

in the range of from about 2 to about 5 weight percent HEC;

in the range of from about 20 to about 89 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent pseudoephedrine sulfate;

in the range of from about 0.1 to about 10 weight percent chlorpheniramine maleate;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2.0 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.

10. A process for making a sustained release oral dosage form comprising wet granulating a medicament with a polymer blend of hydroxypropyl cellulose (HPC) and hydroxyethyl cellulose (HEC), wherein the polymer blend is provided in an amount of about 18 weight percent or less and the ratio of HPC to HEC is in the range of from about 10:

90 to about 90;

10, wherein the polymer blend is provided to control the release of said medicament, to form a homogeneous matrix, then forming the homogenous matrix into a solid oral dosage form.

11. The process of claim 10 wherein the polymer blend contains in the range of from 80 to 62.5 weight percent HPC and in the range of from 20 to 37.5 weight percent HEC.

12. The process of claim 10 wherein the polymer blend contains in the range of from 62.4 to 37.6 weight percent HPC and in the range of from 37.6 to 62.4 weight percent HEC.

13. The process of claim 10 wherein the polymer blend contains the range of from 62.5 to 75 weight percent HEC and in the range of from 37.5 to 25 weight percent HPC.

14. The process of claim 10 wherein the homogeneous matrix comprises in the range of from about 5 to about 12 weight percent HPC;

in the range of from about 2 to about 5 weight percent HEC;

in the range of from about 20 to about 89 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent pseudoephedrine sulfate;

in the range of from about 0.1 to about 10 weight percent chlorpheniramine maleate;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.

15. The process of claim 10 wherein the homogeneous matrix comprises in the range of from about 3 to about 8 weight percent HPC;

in the range of from about 4 to about 8 weight percent HEC;

in the range of from about 20 to about 88 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent terfenadine;

in the range of from about 0.5 to about 5 weight percent of a disintegrant;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.

16. The process of claim 10 wherein the homogeneous matrix comprises in the range of from about 5 to about 10 weight percent HPC;

in the range of from about 1 to about 4 weight percent HEC;

in the range of from about 20 to about 90 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent pseudoephedrine hydrochloride;

in the range of from about 0.5 to about 5 weight percent of a disintegrant;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.

17. A sustained release oral dosage form comprising a homogeneous matrix containing a therapeutically effective amount of a medicament and a polymer blend of hydroxpropyl cellulose (HPC) and hydroxethyl cellulose (HEC) provided in an amount of not more than about 18 weight percent wherein the ratio of HPC to HEC is in the range of from about 10:

90 to about 90;

10, effective to provide a sustained release of said medicament in a solid oral dosage form.

18. The solid dosage form of claim 17 wherein the medicament is an NSAID and one or more medicaments selected from the group consisting of decongestants, bronchodilators, antitussives, antihistamines, non-sedating antihistamines, muscle relaxants, adjuvants and combinations of any of the aforesaid medicaments.

19. The oral dosage form of claim 17 wherein the dosage form comprises in the range of from about 5 to about 12 weight percent HPC;

in the range of from about 2 to about 5 weight percent HEC;

in the range of from about 20 to about 89 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent pseudoephedrine sulfate;

in the range of from about 0.1 to about 10 weight percent chlorpheniramine maleate;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.

20. The oral dosage form of claim 17 wherein the dosage form comprises in the range of from about 3 to about 8 weight percent HPC;

in the range of from about 4 to about 8 weight percent HEC;

in the range of from about 20 to about 88 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent terfenadine;

in the range of from about 0.5 to about 5 weight percent of a disintegrant;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.

21. The oral dosage form of claim 17 wherein the dosage form comprises in the range of from about 5 to about 10 weight percent HPC;

in the range of from about 1 to about 4 weight percent HEC;

in the range of from about 20 to about 90 weight percent acetaminophen;

in the range of from about 3 to about 15 weight percent pseudoephedrine hydrochloride;

in the range of from about 0.5 to about 5 weight percent of a disintegrant;

in the range of from about 0.5 to about 10 weight percent of a binder;

in the range of from about 0.25 to about 2 weight percent of a lubricant; and

in the range of from about 0 to about 60 weight percent of a bulking agent.