Gohel M C, Panchal M K, Jogani V V
Department of Pharmaceutics, L.M. College of Pharmacy, P.O. Box. No. 4011, Navrangpura, Ahmedabad-380009, India.
AAPS PharmSciTech. 2000 Oct 28;1(4):E31. doi: 10.1208/pt010431.
A simple mathematical method to express the deviation in release profile of a test product following Higuchi's kinetics from an ideal Higuchi release profile was developed. The method is based on calculation of area under the curve (AUC) by using the trapezoidal rule. The precision of prediction depends on the number of data points. The method is exemplified for 2 dosage forms (tablets of diltiazem HCl and microspheres of diclofenac sodium) that are designed to release the drug over a 12-hour period. The method can be adopted for the formulations where drug release is incomplete (<100%) or complete (100%) at last sampling time. To describe the kinetics of drug release from the test formulation, zero-order, first-order, Higuchi's, Hixson-Crowell's, and Weibull's models were used. The criterion for selecting the most appropriate model was based on the goodness-of-fit test. The release kinetics of the tablets and microspheres were explained by the Higuchi model. The release profiles of the test batches were slightly below the ideal Higuchi release profile. For the test products, observed percentage deviation from an ideal Higuchi profile is less than 16% for tablets and less than 11% for microspheres. The proposed method can be extended to the modified release formulations that are designed to release a drug over 6, 18, or 24 hours. If the data points are not evenly separated, the ideal drug release profile and AUC are calculated according to the specific sampling time. The proposed method may be used for comparing formulated products during the research and development stage, for quality control of the products, or for promoting products by comparing performance of the test product with that of the innovator's product.
开发了一种简单的数学方法，用于表示遵循Higuchi动力学的测试产品释放曲线与理想Higuchi释放曲线之间的偏差。该方法基于使用梯形法则计算曲线下面积（AUC）。预测精度取决于数据点的数量。以2种剂型（盐酸地尔硫卓片和双氯芬酸钠微球）为例进行说明，这两种剂型设计为在12小时内释放药物。该方法可用于在最后采样时间药物释放不完全（<100%）或完全（100%）的制剂。为了描述测试制剂中药物释放的动力学，使用了零级、一级、Higuchi、Hixson-Crowell和Weibull模型。选择最合适模型的标准基于拟合优度检验。片剂和微球的释放动力学由Higuchi模型解释。测试批次的释放曲线略低于理想的Higuchi释放曲线。对于测试产品，观察到的与理想Higuchi曲线的百分比偏差，片剂小于16%，微球小于11%。所提出的方法可扩展到设计为在6、18或24小时内释放药物的缓释制剂。如果数据点不是均匀分布的，则根据特定的采样时间计算理想的药物释放曲线和AUC。所提出的方法可用于在研发阶段比较配方产品、产品的质量控制，或通过比较测试产品与创新产品的性能来推广产品。
