Mandal U, Ray K K, Gowda Veeran, Ghosh A, Pal T K
Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, S. C. Mallick Road, Kolkata, West Bengal, 700 032, India.
J Pharm Pharmacol. 2007 Jul;59(7):971-6. doi: 10.1211/jpp.59.7.0009.
The aim of this study was to perform an in-vitro-in-vivo correlation (IVIVC) for two 60-mg gliclazide extended-release formulations (Fast and Slow release) given once a day and to compare their plasma concentrations over time. In-vitro release rate data were obtained for each formulation using the USP apparatus II, paddle stirrer at 50 and 100 rev min(-1) in 0.1 M HCl and pH 7.4 phosphate buffer. The similarity factor (f2) was used to analyse the dissolution data. Eighteen healthy subjects participated in the study, conducted according to a completely randomized, two-way crossover design. The formulations were compared using area under the plasma concentration-time curve, AUC(0-infinity), time to reach peak plasma concentration, Tmax, and peak plasma concentration Cmax, while correlation was determined between in-vitro release and in-vivo absorption. A linear correlation model was developed using percent absorbed data versus percent dissolved data from the two formulations. Predicted gliclazide concentrations were obtained by use of a curve fitting equation. Prediction errors were estimated for Cmax and area under the curve AUC(0-infinity) to determine the validity of the correlation. 0.1 M HCl at 50 rev min(-1) was found to be the most discriminating dissolution method. Linear regression analysis of the mean percentage of dose absorbed versus the mean percentage of in-vitro release resulted in a significant correlation (r2 > 0.98) for the two formulations. An average percent prediction error for Cmax was 4.15% for Fast release and 3.99% for Slow release formulation whereas for AUC(0-infinity) it was 6.36% and 4.66% for Fast release and Slow release formulation, respectively.
本研究的目的是对两种每日服用一次的60毫克格列齐特缓释制剂（速释和缓释）进行体外-体内相关性（IVIVC）研究，并比较它们随时间变化的血浆浓度。使用美国药典装置II，在0.1 M盐酸和pH 7.4磷酸盐缓冲液中，以50和100转/分钟的桨式搅拌器，获得每种制剂的体外释放速率数据。相似性因子（f2）用于分析溶出数据。18名健康受试者参与了该研究，研究按照完全随机的双向交叉设计进行。使用血浆浓度-时间曲线下面积（AUC(0-∞)）、达到血浆峰浓度的时间（Tmax）和血浆峰浓度（Cmax）对制剂进行比较，同时确定体外释放与体内吸收之间的相关性。使用两种制剂的吸收百分比数据与溶解百分比数据建立线性相关模型。通过曲线拟合方程获得预测的格列齐特浓度。估计Cmax和曲线下面积AUC(0-∞)的预测误差，以确定相关性的有效性。发现50转/分钟的0.1 M盐酸是最具区分性的溶出方法。对吸收剂量的平均百分比与体外释放的平均百分比进行线性回归分析，结果表明两种制剂具有显著相关性（r2>0.98）。速释制剂Cmax的平均预测误差为4.15%，缓释制剂为3.99%；而对于AUC(0-∞)，速释制剂和缓释制剂分别为6.36%和4.66%。
