Stabilized solid pharmaceutical composition containing acid addition salts of a basic drug and an alkaline stabilizer

• US 5,441,747 A
• Filed: 02/09/1994
• Issued: 08/15/1995
• Est. Priority Date: 09/13/1990
• Status: Expired due to Term

• Current Assignee: N.V. Organon (Merck & Co., Inc.)
• Original Assignee: AKZO NV (Nouryon BV)
• Inventors: van der Ven, Cornelus J. M., de Haan, Pieter
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): LEVY, NEIL S
• Application Number:
  US08/194,182
• Time in Patent Office: 552 Days
• Field of Search: 424/465, 424/499
• US Class Current: 424/465
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Abstract

Disclosed are stabilized dry chemical (e.g. pharmaceutical) compositions containing the water soluble acid addition salt of a poorly soluble basic compound (e.g. mianserin, apomorphine, chlorpromazine, imipramine, or promethazine); an excipient selected from the group consisting of microcrystalline cellulose, lactose, calcium hydrogen phosphate, and mixtures thereof; and a water soluble (>2 mg/ml) alkaline stabilizer. The resulting dry composition are relatively more bioavailable and stable than compositions not containing the water soluble alkaline stabilizer, especially after high temperature (>45°) granulation processes. The process for preparing the dry composition is also more "rugged" with the added water soluble alkaline stabilizer.

Claims

1. A dry pharmaceutical preparation consisting essentially of a water soluble acid addition salt of a poorly soluble basic drug selected from the group consisting of apomorphine, chlorpromazine, imipramine, promethazine, and mianserin;

and excipients selected from the group consisting of microcrystalline cellulose, lactose, and calcium hydrogen phosphate in an amount from about 30 to about 80 percent by weight of the dry pharmaceutical preparation; and

a water soluble alkaline stabilizer in an amount from about 0.5 to about 10 percent by weight of the dry pharmaceutical preparation, wherein said stabilizer is selected from the group consisting of sodium bicarbonate, ammonium carbonate, sodium citrate, dibasic sodium phosphate, anhydrous dibasic sodium biphosphate, diammonium hydrogen phosphate, sodium pyrophosphate and mixtures thereof.

2. The dry pharmaceutical preparation of claim 1 wherein said excipient is calcium hydrogen phosphate.

3. The dry pharmaceutical preparation of claim 2 wherein said poorly soluble basic compound is mianserin.

4. The dry pharmaceutical preparation of claim 3, wherein the water soluble alkaline stabilizer is from about 1 to about 5 percent by weight of the dry pharmaceutical preparation.