Division of Analytical Pharmaceutical Chemistry, Uppsala University, BMC, 751 23, Uppsala, Sweden.
Pharm Res. 2010 Jul;27(7):1309-17. doi: 10.1007/s11095-010-0111-0. Epub 2010 Mar 27.
To evaluate the usefulness of a miniaturized rotating disk equipment for the determination of factors influencing the in vitro dissolution rate, G, of a model basic drug substance (terfenadine) in different aqueous media, using experimental design and multivariate data analysis. The apparent solubility, S, was included in the chemometric study.
The dissolution rate was determined with a miniaturized rotating disk apparatus and the solubility by shake-flask methodology. Media were based on acetate, phosphate or maleate buffers-the latter used in fasted state simulated intestinal fluid (FaSSIF-V2). The chemometric analyses included fractional factorial design, principal component analysis (PCA) and orthogonal partial least squares (OPLS). Quantifications were made with a RP-HPLC-DAD system.
The most influential factor for both G and S of terfenadine in the different media was pH. Apart from the ionic strength and sodium chloride concentration in the acetate medium, the effects of the other variables were insignificant, implying no wetting effect of the surfactants.
The miniaturized rotating disk equipment was suitable to use, in conjunction with the chemometric analyses, in the evaluation of the factors affecting the in vitro dissolution rate. The apparent solubility was found to be influenced by the same factors as G.
评估微型旋转盘设备在不同水性介质中测定模型碱性药物（特非那定）体外溶出速率 G 影响因素的有用性，采用实验设计和多元数据分析。表观溶解度 S 也包含在化学计量学研究中。
采用微型旋转盘装置测定溶出速率，采用摇瓶法测定溶解度。介质基于醋酸盐、磷酸盐或马来酸盐缓冲液-后者用于模拟空腹状态下的肠道液（FaSSIF-V2）。化学计量学分析包括部分因子设计、主成分分析（PCA）和正交偏最小二乘（OPLS）。定量采用反相高效液相色谱-二极管阵列检测系统进行。
在不同介质中，特非那定的 G 和 S 的最主要影响因素均为 pH。除醋酸盐介质中的离子强度和氯化钠浓度外，其他变量的影响不显著，这意味着表面活性剂没有润湿作用。
微型旋转盘设备与化学计量学分析相结合，适合用于评估影响体外溶出速率的因素。发现表观溶解度受与 G 相同的因素影响。
