Flufenamic acid is a nonsteroidal anti-inflammatory drug characterized by a low solubility and a variable oral bioavailability. Flufenamic acid is present in the commercial products in two polymorphic enantiotropic forms (Form I and III). Bioinequivalence was observed for commercial solid dosage forms due to the different dissolution rate of batches. Aim of this work is the full characterization of the solid state properties of flufenamic acid in order to evidence reasons of its variable dissolution properties. Two different batches of pure drug obtained by different suppliers were fully characterized. In order to evaluate the effect of the technological processes used for tablet production, the powders were submitted to grinding, kneading, and compression. Thermal analysis and X-ray diffraction studies proved that the drug was provided by both suppliers as Form I, Form III is obtained by recrystallization from ethanol or ethanol/water of both batches and no changes were observed after the different mechanical treatments. No difference was observed between the two forms in terms of equilibrium solubility values. Dissolution rate studies evidenced a difference between the two batches due to their different particle size, which disappeared after sieving. Interestingly, a significant difference in terms of intrinsic dissolution rate and surface wettability of the two compacted powders was observed, even after sieving, probably related to a different behavior of the two powder samples under compaction. These results should be taken into account, during a tablet formulation, in order to obtain a reproducible dissolution performance of the drug, regardless of its original supplier.

中文翻译：

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固态性质对氟芬那酸溶解性能的作用。

氟苯那酸是一种非甾体类抗炎药，其特征在于溶解度低和口服生物利用度可变。氟虫酰胺酸以两种多晶型对映体形式（形式I和III）存在于商品中。由于批次的溶解速率不同，因此观察到商业固体剂型的生物不当性。这项工作的目的是对氟苯那酸的固态性质进行全面表征，以证明其可变溶出性质的原因。充分表征了由不同供应商获得的两批不同的纯药物。为了评估用于片剂生产的工艺过程的效果，将粉末进行研磨，捏合和压片。热分析和X射线衍射研究证明，该药物由两家供应商提供，均为I型，III型是通过两批乙醇或乙醇/水重结晶而获得的，经过不同的机械处理后未观察到变化。就平衡溶解度值而言，两种形式之间未观察到差异。溶出度研究表明，由于两批物料的粒径不同，它们之间存在差异，但在筛分后消失了。有趣的是，即使在筛分后，在两种压实粉末的固有溶解速率和表面润湿性方面也观察到显着差异，这可能与两种粉末样品在压实下的不同行为有关。在片剂配制过程中应考虑到这些结果，