Drug-excipient incompatibility studies of the dipeptide angiotensin-converting enzyme inhibitor, moexipril hydrochloride: dry powder vs wet granulation.
The drug-excipient incompatibility screen for moexipril hydrochloride (1) using various isothermal stress methods is reported herein. It was found that most of the commonly used filters, disintegrants, lubricants, glidants, and coating agents were incompatible with 1 in dry powder mixtures; moisture and basic (or alkalizing) agents were determined to be the dominant destabilizing factors. In wet granulations, basic agents, however, were found to suppress drug degradation even in the presence of moisture. Supported by the product distribution studies, the stabilization is proposed to involve the neutralization of the acidic drug by the basic excipients.
Gu
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Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California 94304.
Strickley
R G
RG
Chi
L H
LH
Chowhan
Z T
ZT
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004344:Drug Incompatibility; D005079:Excipients; D006813:Humidity; D007546:Isoquinolines / Q000032:analysis*; D007785:Lactose; D011208:Powders; D044005:Tetrahydroisoquinolines; D013816:Thermodynamics
D000806:Angiotensin-Converting Enzyme Inhibitors; D005079:Excipients; D007546:Isoquinolines; D011208:Powders; D044005:Tetrahydroisoquinolines; D007785:Lactose; C058302:moexipril