Narazaki Ryuichi, Sanghvi Ritesh, Yalkowsky Samuel H
College of Pharmacy, University of Arizona, 1703 East Mabel, Tucson, Arizona 85721-0207, USA.
Mol Pharm. 2007 Jul-Aug;4(4):550-5. doi: 10.1021/mp070007o. Epub 2007 May 26.
An equation is developed for estimating the precipitation that may occur upon diluting or injecting a (pH-)solubilized drug formulation. Since it is based on equilibrium, it is the worst case scenario for precipitation. This equation can be programmed in any commercially available spread sheet program such as Excel. According to the proposed equation, the type and the strength of the buffer species are the most significant factors that affect the pH and solubility of a drug in its microenvironment during dilution. To demonstrate the utility and robustness of the proposed equation, experimental measurements were performed using phenytoin as the model drug. The result suggests that the proposed equation can be used to indicate the possibility and the degree of precipitation that would occur upon injection. This provides a useful tool for the design of a successful pH-controlled solution formulation.
开发了一个方程式，用于估算稀释或注射（pH-）增溶药物制剂时可能发生的沉淀。由于它基于平衡，所以是沉淀的最坏情况。该方程式可以在任何市售的电子表格程序（如Excel）中编程。根据所提出的方程式，缓冲物质的类型和强度是稀释过程中影响药物在其微环境中的pH值和溶解度的最重要因素。为了证明所提出方程式的实用性和稳健性，使用苯妥英作为模型药物进行了实验测量。结果表明，所提出的方程式可用于指示注射时发生沉淀的可能性和程度。这为设计成功的pH控制溶液制剂提供了一个有用的工具。
