The Stability of a Novel Carbapenem Antibiotic, Meropenem (SM-7338), in a Solid State Formulation for Injection

Abstract

A formulation of meropenem, a novel carbapenem antibiotic for injection, was developed as a vial filled with a mixture of meropenem and dried sodium carbonate. During the design phase, we studied the effect of water in the formulation on the stability of meropenem in the solid state. Meropenem is obtained as trihydrate, whose moisture content is 12.35% and is nonhygroscopic. Dehydrated meropenem, whose moisture content was 3.4%, took up moisture quickly even under low humidity (33% RH). Also, the chemical stability of dehydrated meropenem was poor compared with that of untreated meropenem, which is quite stable. Degradation of meropenem by free water was considered as a possible cause of the poor stability. Degradation of meropenem due to liberation of its crystal water to free water was also observed when meropenem was micronized by pneumatic pulverization. Crystal water of meropenem was found to stay bound and to be almost inert in the formulation. Thus, meropenem injection formulation is stable for long time at room temperature. © 1993, The Pharmaceutical Society of Japan. All rights reserved.