Bendas Ehab R
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Arch Pharm Res. 2009 Sep;32(9):1317-29. doi: 10.1007/s12272-009-1918-2. Epub 2009 Sep 26.
The aim of this study was to employ two different mathematical approaches: first, a convolution approach using computer software; second, a mathematical calculation exploiting Wagner-Nelson calculation to predict in vivo plasma concentration-time profile from the in vitro release study for the once daily formulations of a model drug diltiazem hydrochloride. The once daily extended release tablets (120 mg) were prepared by the wet granulation technique. Ethanol or ethanolic solutions of ethylcellulose (N22), were used as granulating agents along with hydrophilic matrix polymers like hydroxypropyl methylcellulose (HPMC) (K 15M). The granules showed satisfactory flow properties, compressibility, moisture content and drug content. All the tablet formulations showed acceptable properties and complied with pharmacopeial limits. The in vitro drug release study revealed that formula F7-T which contains drug: HPMC ratio 1:1 and 20 mg of ethylcellulose was able to sustain the drug release for 24 h and satisfied the USP dissolution limits. Fitting the in vitro drug release data to Korsmeyer-Peppas equation indicated that the mechanism of drug release could be zero-order. The capsule formulation F14-C which consists of drug: HPMC ratio 1:2, 12 mg of ethylcellulose and 20 mg of polyox 100 showed in vitro drug release similar to the tablet F7-T using the similarity factor (f 2). The mechanism of drug release could be coupled diffusion, and polymer matrix relaxation. The percent dissolved data from the two formulations were used as input function to predict the in vivo plasma data by the two approaches (Convolution by Kinetica software and Wagner-Nelson calculation). The two methods were validated by prediction of plasma data from in vitro release data of FDA approved 300 mg extended release capsule. Prediction errors were estimated for Cmax and area under the curve (AUC) to determine the validity of the methods. The percent prediction error for each parameter is not exceeding 15%.
第一，使用计算机软件的卷积方法；第二，利用Wagner-Nelson计算的数学计算方法，从模型药物盐酸地尔硫䓬每日一次制剂的体外释放研究中预测体内血浆浓度-时间曲线。通过湿法制粒技术制备了每日一次的缓释片（120 mg）。乙醇或乙基纤维素（N22）的乙醇溶液与亲水性基质聚合物如羟丙基甲基纤维素（HPMC）（K 15M）一起用作制粒剂。颗粒显示出令人满意的流动性、可压性、水分含量和药物含量。所有片剂制剂均显示出可接受的性质，并符合药典规定。体外药物释放研究表明，含有药物与HPMC比例为1:1和20 mg乙基纤维素的配方F7-T能够维持药物释放24小时，并满足美国药典的溶出限度。将体外药物释放数据拟合到Korsmeyer-Peppas方程表明，药物释放机制可能是零级。由药物与HPMC比例为1:2、12 mg乙基纤维素和20 mg聚氧乙烯100组成的胶囊制剂F14-C，使用相似性因子（f 2）显示出与片剂F7-T相似的体外药物释放。药物释放机制可能是耦合扩散和聚合物基质松弛。将两种制剂的溶出百分比数据用作输入函数，通过两种方法（Kinetica软件卷积法和Wagner-Nelson计算法）预测体内血浆数据。通过预测FDA批准的300 mg缓释胶囊的体外释放数据的血浆数据来验证这两种方法。估计了Cmax和曲线下面积（AUC）的预测误差，以确定方法的有效性。每个参数的预测误差百分比不超过15%。
