University of the Witwatersrand, Department of Pharmacy and Pharmacology, Division of Pharmaceutics, Johannesburg, South Africa.
Curr Drug Deliv. 2010 Jan;7(1):5-12. doi: 10.2174/156720110790396490.
Dissolution testing with subsequent analysis is considered as an imperative tool for quality evaluation of the combination rifampicin-isoniazid (RIF-INH) combination. Partial least squares (PLS) regression has been successfully undertaken to select suitable predictor variables and to identify outliers for the generation of equations for RIF and INH determination in fixed-dose combinations (FDCs). The aim of this investigation was to ascertain the applicability of the described technique in testing a novel oral FDC anti-TB drug delivery system and currently available two-drug FDCs, in comparison to the United States Pharmacopeial method for analysis of RIF and INH Capsules with chromatographic determination of INH and colorimetric RIF determination. Regression equations generated employing the statistical coefficients satisfactorily predicted RIF release at each sampling point (R(2)>or=0.9350). There was an acceptable degree of correlation between the drug release data, as predicted by regressional analysis of UV spectrophotometric data, and chromatographic and colorimetric determination of INH (R(2)=0.9793 and R(2)=0.9739) and RIF (R(2)= 0.9976 and R(2)=0.9996) for the two-drug FDC and the novel oral anti-TB drug delivery system, respectively. Regressional analysis of UV spectrophotometric data for simultaneous RIF and INH prediction thus provides a simplified methodology for use in diverse research settings for the assurance of RIF bioavailability from FDC formulations, specifically modified-release forms.
溶出度试验及后续分析被认为是评估利福平-异烟肼（RIF-INH）复方制剂质量的重要手段。偏最小二乘法（PLS）回归已成功用于选择合适的预测变量，并识别出用于生成固定剂量复方制剂（FDC）中 RIF 和 INH 测定方程的异常值。本研究旨在确定所描述的技术在测试新型口服抗结核药物 FDC 给药系统和当前市售的两种药物 FDC 中的适用性，该技术与美国药典法相比，可用于分析 RIF 和 INH 胶囊，采用 INH 的色谱测定和 RIF 的比色测定。采用统计学系数生成的回归方程能够很好地预测每个采样点的 RIF 释放情况（R(2)>or=0.9350）。通过对紫外分光光度数据的回归分析预测药物释放数据与 INH 的色谱和比色测定（R(2)=0.9793 和 R(2)=0.9739）和 RIF 的相关性（R(2)=0.9976 和 R(2)=0.9996）具有可接受的程度，对于两种药物 FDC 和新型口服抗结核药物 FDC，通过回归分析预测 RIF 和 INH 的紫外分光光度数据提供了一种简化的方法，用于确保从 FDC 制剂，特别是缓释制剂中获得 RIF 的生物利用度。
