Dey M, Enever R, Kraml M, Prue D G, Smith D, Weierstall R
Department of Pharmaceutical Sciences, Wyeth-Ayerst Research, Rouses Point, New York 12979.
Pharm Res. 1993 Sep;10(9):1295-300. doi: 10.1023/a:1018913628568.
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.
将暴露于高相对湿度和温度下的依托度酸胶囊的溶出度和生物利用度与室温（RT）下储存的胶囊进行比较。使用美国药典篮式装置，在37℃下以100转/分钟的转速，在900 mL pH 7.5磷酸盐缓冲液（0.05 M）中评估加速试验胶囊和对照胶囊的溶出度。还通过向溶出介质中添加酶（胰酶，1%，w/v）来评估暴露于加速试验条件下的依托度酸胶囊的溶出度。将暴露于加速试验条件下的依托度酸胶囊在犬和人体中的生物利用度与在室温条件下储存的胶囊进行比较。暴露于加速试验条件下的200 mg和300 mg胶囊未通过溶出度（无酶）标准[30分钟内释放不少于85%（80% Q）]。然而，添加酶后，所有胶囊均符合标准。犬体内200 mg和300 mg依托度酸胶囊的吸收速率和程度与通过溶出度标准的室温储存胶囊相当。同样，在24名成年男性志愿者中，暴露于加速试验条件下未通过溶出度标准的300 mg胶囊中依托度酸的生物利用度与对照胶囊相当。因此，用酶进行的体外溶出试验能更好地反映加速试验胶囊在体内的性能。
