Stable pharmaceutical compositions without a stabilizer

• US 20040101556A1
• Filed: 11/21/2002
• Published: 05/27/2004
• Est. Priority Date: 11/21/2002
• Status: Active Grant

• Current Assignee: Andrx Pharmaceuticals LLC (Teva Pharmaceutical Industries Limited)
• Original Assignee: Andrx Pharmaceuticals LLC (Teva Pharmaceutical Industries Limited)
• Inventors: Cheng, Xiu Xiu, Li, Boyong
• Granted Patent: US 6,893,660 B2
• Time in Patent Office: Days
• US Class Current: 424/471
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

Stabilized controlled release pharmaceutical preparations are disclosed in which active ingredient degradation is prevented without the use of a stabilizer. The active ingredient is sealed away from excipients that can adversely affect stability by sealing the excipients rather than the active ingredient. The preparations are substantially unaffected by exposure to storage conditions of elevated temperature and/or elevated relative humidity.

Claims

8. A pharmaceutical composition in solid form comprising pharmaceutically active ingredients combined with excipients having a negative effect on stability, combined with a sealing component.

2. The method for stabilizing the pharmaceutically active component of claim 1, wherein said composition retains at least 85% w/w of undegraded active ingredient after storage for 3 months at about 40°

C. and about 75% relative humidity.

9. The composition of claim 8, wherein the pharmaceutically active ingredients comprise bupropion.

11. The tablet or capsule of claim 10, wherein the amount of bupropion ranges from about 75 to about 300 mg.

12. A pharmaceutical composition of claim 8 comprising:

(a) bupropion hydrochloride;

(b) a compressible tableting filler;

(c) a glidant;

(d) a lubricant; and

(e) a component comprising a mixture of;

(i) a low molecular weight polyethylene oxide;

(ii) a high molecular weight polyethylene oxide; and

(iii) hydroxypropyl cellulose;

as a sealing component to seal (i) and (ii).

13. A pharmaceutical composition of claim 12 comprising from about 50 to about 400 mg bupropion hydrochloride;

from about 40 to about 80 mg polyethylene oxide (M. W. 200,000);

from about 30 to about 70 mg polyethylene oxid (M. W. 5,000,000);

from about 5 to about 20 mg hydroxypropylcellulose;

from about 15 to about 40 mg lactose anhydrous;

from about 0.5 to about 5 mg colloidal silicon dioxide and from about 0.25 to about 2.5 mg magnesium stearate.

14. A pharmaceutical composition of claim 13, comprising by weight, approximately,

10-1. The tablet or capsule of claim 10 wherein the amount of bupropion hydrochloride is 150 mg.

11-2. The composition of claim 8 wherein the amount of sealing component comprises 2% to 20% of the total weight.

15. An improved method for preparing a solid dosage delivery form comprising an active ingredient and excipients that can adversely affect the stability of said active ingredient, the improvement comprising seal coating said excipients prior to adding said excipients to said active ingredient.

16. An improved method as defined in claim 15 where said active ingredient is selected from the group consisting of algicides, antioxidants, air purifiers, biocides, bactericides, catalysts, chemical reactants, disinfectants, fungicides, fermentation agents, fertility inhibitors, fertility promoters, germicides, herbicides, insecticides, microorganism attenuators, pesticides, plant growth promoters, plant growth inhibitors, preservatives, rodenticides, sterilization agents, sex sterilants, and mixtures of any of the foregoing.

17. An improved method as defined in claim 16 where said active ingredient comprises a pharmaceutical drug.

18. An improved method as defined in claim 17, where said pharmaceutical drug comprises bupropion hydrochloride.