Estimation of Drug Precipitation upon Dilution of pH-Controlled Formulations

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• 作者：Ryuichi Narazaki ; Ritesh Sanghvi ; Samuel H. Yalkowsky
• 刊名：Molecular Pharmaceutics
• 出版年：2007
• 出版时间：August 2007
• 年：2007
• 卷：4
• 期：4
• 页码：550 - 555
• 全文大小：166K
• 年卷期：v.4,no.4(August 2007)
• ISSN：1543-8392

文摘

An equation is developed for estimating the precipitation that may occur upon dilutingor injecting a (pH-)solubilized drug formulation. Since it is based on equilibrium, it is the worstcase scenario for precipitation. This equation can be programmed in any commercially availablespread sheet program such as Excel. According to the proposed equation, the type and thestrength of the buffer species are the most significant factors that affect the pH and solubility ofa drug in its microenvironment during dilution. To demonstrate the utility and robustness of theproposed equation, experimental measurements were performed using phenytoin as the modeldrug. The result suggests that the proposed equation can be used to indicate the possibilityand the degree of precipitation that would occur upon injection. This provides a useful tool forthe design of a successful pH-controlled solution formulation.