Ayres J W, Huang H P, Albert K
J Pharm Sci. 1984 Nov;73(11):1629-34. doi: 10.1002/jps.2600731135.
Dissolution profiles for 62 lots of tolbutamide tablets from six manufacturers have been characterized using the USP paddle-stirrer apparatus. Results of paddle-stirrer dissolution for percent drug dissolved at 10, 20, and 30 min correlated well (r2 = 0.7444) with results from the USP rotating-basket test for 39 lots of tolbutamide. Interlot and intralot variability in tolbutamide dissolution was highly dependent on the manufacturer. For one product, the intralot range (for six paddle-stirred tablets) of percent drug dissolved after 30 min was 50-68% while the maximum interlot range for mean dissolution was 58-104%. One lot failed to meet both the rotating-basket and the paddle-stirrer dissolution specifications. Tablet response to aging at 60, 75, and 98% relative humidity over time was also highly manufacturer specific. The innovator's product repeatedly dissolved well when fresh or aged at all humidities. Dissolution from some generic tablets was dramatically depressed by humidity aging, even after only 3 d. Pretreatment of tablets with simulated gastric fluid modified the dissolution profile of one poorly dissolving lot of tablets. Results indicate that manufacturing quality control is highly variable among tolbutamide tablets.
已使用美国药典桨板搅拌装置对来自六个制造商的62批甲苯磺丁脲片的溶出曲线进行了表征。桨板搅拌法在10、20和30分钟时药物溶出百分比的结果与39批甲苯磺丁脲的美国药典转篮试验结果相关性良好（r2 = 0.7444）。甲苯磺丁脲溶出的批间和批内变异性高度依赖于制造商。对于一种产品，30分钟后药物溶出百分比的批内范围（六片桨板搅拌片）为50 - 68%，而平均溶出的最大批间范围为58 - 104%。一批产品未能同时满足转篮法和桨板搅拌法的溶出规格。随着时间推移，片剂在60%、75%和98%相对湿度下对老化的反应也高度因制造商而异。创新者的产品在新鲜时或在所有湿度下老化后均能反复良好溶出。一些仿制药片的溶出在湿度老化后，即使仅3天，也会显著降低。用模拟胃液对片剂进行预处理改变了一批难溶片剂的溶出曲线。结果表明，甲苯磺丁脲片的生产质量控制差异很大。
