High-Throughput Study of Phenytoin Solid Dispersions: Formulation Using an Automated Solvent Casting Method, Dissolution Testing, and Scaling-Up

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• 作者：Valé ; ry Barillaro ; Paolo P. Pescarmona ; Michiel Van Speybroeck ; Thao Do Thi ; Jan Van Humbeeck ; Jan Vermant ; Patrick Augustijns ; Johan A. Martens ; Guy Van Den Mooter
• 刊名：Journal of Combinatorial Chemistry
• 出版年：2008
• 出版时间：September 8, 2008
• 年：2008
• 卷：10
• 期：5
• 页码：637-643
• 全文大小：164K
• 年卷期：v.10,no.5(September 8, 2008)
• ISSN：1520-4774

文摘

A high-throughput experimentation method for studying the dissolution of phenytoin, a poorly water soluble drug, was developed and validated. Solid dispersions with 12 excipients (7 polymers and 5 surfactants) were prepared and tested. Each excipient was screened with three drug loadings: 10, 20, and 40% (w/w). Each solid dispersion was prepared in triplicate, for a total of 108 samples. The drug dissolution was studied in simulated gastric fluid without pepsin plus 1% sodium laurylsulfate. This study led to the identification of three improved formulations, exhibiting an extent of dissolution higher than 90% after both 30 and 60 min. The HTE results could be reproduced at a larger scale using a conventional solvent evaporating method, proving the reliability of the HTE protocol.