The dissolution and bioavailability of etodolac from capsules exposed to conditions of high relative humidity and temperatures.

Abstract

The dissolution and bioavailability of etodolac from capsules exposed to high relative humidity and temperature were compared to those from capsules stored at room temperature (RT). Dissolution of stressed and control capsules was evaluated using a USP basket apparatus at 100 rpm with 900 mL pH 7.5 phosphate buffer (0.05 M) at 37 degrees C. The dissolution of etodolac from capsules exposed to stressed conditions was also evaluated with enzymes (pancreatin, 1%, w/v) added to the dissolution medium. The bioavailability of etodolac from capsules exposed to stressed conditions was compared in both dogs and humans to capsules stored at RT conditions. Capsules, 200 and 300 mg, exposed to stressed conditions failed the dissolution (without enzymes) specification [not less than 85% released (80% Q) in 30 min]. However, upon enzyme addition, all capsules met the specification. The rate and extent of absorption from these 200 and 300 mg etodolac capsules in dogs were equivalent to those from capsules stored at RT conditions that passed the dissolution specification. Similarly, the bioavailability of etodolac from 300 mg capsules that failed the dissolution specification upon exposure to stressed conditions was equivalent to that of control capsules in 24 adult male volunteers. Thus, an in vitro dissolution test with enzymes provides a better indication of stressed capsule performance in vivo.