Stable pharmaceutical compositions without a stabilizer

• US 6,893,660 B2
• Filed: 11/21/2002
• Issued: 05/17/2005
• Est. Priority Date: 11/21/2002
• Status: Expired due to Term

• Current Assignee: Andrx Pharmaceuticals LLC (Teva Pharmaceutical Industries Limited)
• Original Assignee: Andrx Pharmaceuticals (NC), Inc. (Abbvie Incorporated)
• Inventors: Cheng, Xiu Xiu, Li, Boyong
• Primary Examiner(s): Spear, James M.
• Application Number:
  US10/301,474
• Publication Number:
  US 20040101556A1
• Time in Patent Office: 908 Days
• Field of Search: 424/464, 424/465, 424/489, 424/451, 424/452
• US Class Current: 424/464
• 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

1. A method for stabilizing pharmaceutical preparations in solid dosage forms by:

preventing direct contact between excipients that have a negative effect on stability of pharmaceutically active ingredients, said method comprising;

a) adding a sealing component to said excipients to form a sealed excipient component; and

b) combining said sealed excipient component with a composition comprising pharmaceutically active components to form a stable composition, wherein the sealed excipients comprise a combination of low molecular weight and high molecular weight polyethylene oxides.

2. The method of claim 1, wherein the sealed excipient ratio of high molecular weight to low molecular weight polyethylene oxides is 1:

1.24 (wt./wt.).

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

4. A pharmaceutical composition of claim 3 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 oxide (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.

5. A pharmaceutical composition of claim 4, comprising by weight, approximately,

bupropion hydrochloride150.0 mg