The Effect of Selected Direct Compression Excipients on the Stability of Aspirin as a Model Hydrolyzable Drug

Abstract

The stability of a moisture sensitive drug is normally studied in relation to packaging which prevents water vapor ingress or minimizes its effect by using dessicants in a container. However, excipients contain intrinsic water which may degrade the drug. This paper deals with the stability of aspirin, as a model hydrolyzable drug, in combination with excipients having either hydrate water (dibasic calcium phosphate dihydrate and lactose) or variable adsorbed moisture depending upon environmental conditions (microcrystalline cellulose and pregelatinized starch). Tablets containing 10 and 50 per cent aspirin with these excipients were stored in open and closed bottles at various temperatures and humidities. Pregelatinized starch based tablets were stable in closed containers for 30 weeks while tablets containing microcrystalline cellulose or dibasic calcium phosphate dihydrate were unstable with respect to USP salicylic acid content. The stability of lactose based tablets was dependent on aspirin content. In some cases tablets in open bottles were more stable than those in closed bottles. This indicates that water liberated from excipients, if allowed to remain in a closed package, will affect the stability of hydrolyzable drugs. Product stability programs must be properly designed to detect instability from this source.