Takka Sevgi, Sakr Adel, Goldberg Arthur
Industrial Pharmacy Program, University of Cincinnati, Medical Center, Cincinnati, OH, USA.
J Control Release. 2003 Feb 14;88(1):147-57. doi: 10.1016/s0168-3659(02)00490-x.
The aim of this study was to develop an in-vitro-in-vivo correlation (IVIVC) for two buspirone hydrochloride extended release formulations and to compare their plasma concentrations over time with the commercially available immediate release (IR) tablets. In vitro release rate data were obtained for each formulation using the USP Apparatus 2, paddle stirrer at 50 and 100 rpm in 0.1 M HCl and pH 6.8 phosphate buffer. A three-way crossover study in 18 healthy subjects studied a 30 mg "Fast" (12 h) and 30 mg "Slow" (24 h) formulation of buspirone hydrochloride given once a day, and 2x15 mg immediate release tablets dosed at a 12 h interval. The similarity factor (f(2)) was used to analyze the dissolution data. A linear correlation model was developed using percent absorbed data and percent dissolved data from the two formulations. Predicted buspirone hydrochloride concentrations were obtained by use of a curve fitting equation for the immediate release data to determine the volume of distribution and fraction absorbed constants. Prediction errors were estimated for C(max) and area under the curve (AUC) to determine the validity of the correlation. pH 6.8 at 50 rpm was found to be the most discriminating dissolution method. Linear regression analyses of the mean percentage of dose absorbed versus the mean in vitro release resulted in a significant correlation (r(2)>0.95) for the two formulations. An average percent prediction error for C(max) was -0.16%, but was 16.1%, for the AUCs of the two formulations.
本研究的目的是建立两种盐酸丁螺环酮缓释制剂的体外-体内相关性（IVIVC），并将它们随时间变化的血浆浓度与市售速释（IR）片剂进行比较。使用美国药典装置2，在0.1 M盐酸和pH 6.8的磷酸盐缓冲液中，以50和100 rpm的转速用桨式搅拌器获得每种制剂的体外释放速率数据。在18名健康受试者中进行的一项三交叉研究，研究了每天服用一次的30 mg“快速”（12小时）和30 mg“慢速”（24小时）盐酸丁螺环酮制剂，以及以12小时间隔给药的2×15 mg速释片剂。相似性因子（f(2)）用于分析溶出数据。使用两种制剂的吸收百分比数据和溶解百分比数据建立线性相关模型。通过对速释数据使用曲线拟合方程来确定分布容积和吸收分数常数，从而获得预测的盐酸丁螺环酮浓度。估计了C(max)和曲线下面积（AUC）的预测误差，以确定相关性的有效性。发现50 rpm时pH 6.8是最具区分性的溶出方法。对吸收剂量的平均百分比与平均体外释放进行线性回归分析，结果表明两种制剂具有显著相关性（r(2)>0.95）。两种制剂C(max)的平均预测误差百分比为-0.16%，但AUC的平均预测误差百分比为16.1%。
