Stabilization of quinapril using magnesium oxide

Abstract

The present invention is directed to ACE inhibitor-containing compositions stabilized by the presence of magnesium oxide. Preferably, the ACE inhibitor, quinapril, is protected from certain forms of degradation when prepared in a pharmaceutical composition consisting essentially of magnesium oxide as the stabilizing agent. The presence of magnesium oxide also lends itself to favorable processing conditions during the manufacture of ACE inhibitor-containing compositions, especially processing by wet granulation.

Description

FIELD OF THE INVENTION [0001] The present invention is directed to ACE inhibitor-containing compositions stabilized by the presence of magnesium oxide. Preferably, the ACE inhibitor, quinapril, is protected from certain forms of degradation when prepared in a pharmaceutical composition consisting essentially of magnesium oxide as the stabilizing agent. The presence of magnesium oxide also lends itself to favorable processing conditions during the manufacture of ACE inhibitor-containing compositions, especially processing by wet granulation. BACKGROUND OF THE INVENTION [0002] Certain ACE (Angiotensin Converting Enzyme) inhibitors, which are useful as antihypertensives, are susceptible to certain types of degradation. Specifically, quinapril and structurally-related drugs can degrade via (1) cyclization via internal nucleophilic attack to form substituted diketopiperazines, (2) hydrolysis of the side-chain ester group, and (3) oxidation to form products having often unwanted coloratio...

AI Technical Summary

Benefits of technology

"The patent text describes a new way to make medication containing ACE inhibitors that are stable and can be formulated into tablets. The method uses magnesium oxide as a stabilizer to prevent the ACE inhibitor from breaking down and to improve the manufacturing process. The resulting medication is more stable, resistant to discoloration, and can be used in combination with other drugs. The use of magnesium oxide also results in improved processing and decreases the cost and labor of the manufacturing process."

Problems solved by technology

Certain ACE (Angiotensin Converting Enzyme) inhibitors, which are useful as antihypertensives, are susceptible to certain types of degradation.

Magnesium carbonate hydroxide is a white, bulky powder which is difficult to formulate into tablets because of its poor compressibility, moldability, and flowability.

However, it is laborious, involving considerable material handling, as well as several processing steps, and therefore it is costly.

The labor and cost so characteristic of wet granulation processes are common when compounds like magnesium carbonate hydroxide are mixed with ACE inhibitors like quinapril HCl.

Magnesium carbonate hydroxide is also problematic to manufacturers because of sourcing concerns.

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