Cascone Sara
Department of Industrial Engineering, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano, (SA), Italy.
Eur J Pharm Sci. 2017 Aug 30;106:352-361. doi: 10.1016/j.ejps.2017.06.021. Epub 2017 Jun 14.
During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach. Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.
在过去几十年中，美国食品药品监督管理局（FDA）大力推动了药物体外溶出度的研究，以确定其与药物体内生物利用度的关系。在这项工作中，使用不同的溶出方法对含有双氯芬酸（一种BCS II类药物）的速释和缓释制剂进行了研究。对在美国药典装置II和美国药典装置IV中获得的释放曲线进行了评估和比较，以确定流体动力学条件对释放的影响。评估了混合条件（即美国药典装置II中的桨叶转速或美国药典装置IV中的入口流速）对药物释放的影响，发现对于缓释制剂，它们对释放曲线没有显著影响。使用一种模拟消化过程中胃蠕动收缩的体外装置来模拟更接近真实生理状态的流体动力学。如果在人工胃中进行测试，发现这些片剂的行为方式完全不同。分别使用非模型依赖和模型依赖方法来比较和拟合溶出曲线。拟合因子用作两条溶出曲线相似性的指标；使用模型方程（如零级、一级或Korsmeyer-Peppas方程）来拟合实验数据。通过使用相关因子和赤池信息准则确定最佳拟合模型，确定了决定每种制剂行为的传输现象。
