Simamora P, Pinsuwan S, Surakitbanharn Y, Yalkowsky S H
Department of Pharmaceutical Sciences, University of Arizona, Tucson, USA.
PDA J Pharm Sci Technol. 1996 Mar-Apr;50(2):123-8.
Injectable and infusion formulations of dexverapamil are evaluated for their potential to produce phlebitis. The evaluation technique utilizes two independent in vitro methods and two in vivo methods to screen a pH solubilized drug for its potential to induce phlebitis due to precipitation at the injection site. One method is based upon a theoretical calculation that simulates the change of solubility upon dilution. Its predictions are confirmed by the second method which consists of an in vitro precipitation experiment. Thermal and visual evaluations are then obtained from an in vivo rabbit ear injection. Dexverapamil formulations that have low buffering capacity are shown to contribute to the incidence of phlebitis to a greater extent than the properly buffered formulations. The calculation and the in vitro precipitation experiment are found to be useful in formulating pH solubilized parenterals. They enable the formulator to optimize pH, drug concentration, and buffer concentration without the need for animal studies. The results of this study show the importance of selecting a buffer that provides adequate buffer capacity in the formulations.
对右维拉帕米的注射剂和输液剂进行了静脉炎产生可能性的评估。评估技术采用两种独立的体外方法和两种体内方法，以筛选经pH值增溶的药物因在注射部位沉淀而诱发静脉炎的可能性。一种方法基于模拟稀释时溶解度变化的理论计算。其预测结果通过由体外沉淀实验组成的第二种方法得到证实。然后通过体内兔耳注射获得热学和视觉评估结果。结果表明，与缓冲适当的制剂相比，缓冲能力低的右维拉帕米制剂在更大程度上导致静脉炎的发生。发现该计算和体外沉淀实验在配制经pH值增溶的肠胃外给药制剂时很有用。它们使配方设计师能够优化pH值、药物浓度和缓冲剂浓度，而无需进行动物研究。本研究结果表明了在制剂中选择具有足够缓冲能力的缓冲剂的重要性。
