Charumanee Suporn, Okonogi Siriporn, Sirithunyalug Jakkapan, Wolschann Peter, Viernstein Helmut
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mail 50200, Thailand.
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna 1090, Austria.
Sci Pharm. 2016 Oct 18;84(4):694-704. doi: 10.3390/scipharm84040694.
The aim of the study was to investigate the solubility of piroxicam (Prx) depending on the inclusion complexation with various cyclodextrins (CDs) and on ethanol as a co-solvent. The phase-solubility method was applied to determine drug solubility in binary and ternary systems. The results showed that in systems consisting of the drug dissolved in ethanol-water mixtures, the drug solubility increased exponentially with a rising concentration of ethanol. The phase solubility measurements of the drug in aqueous solutions of CDs, β-CD and γ-CD exhibited diagrams of A-type, whereas 2,6-dimethyl-β-CD revealed A-type. The destabilizing effect of ethanol as a co-solvent was observed for all complexes regardless of the CD type, as a consequence of it the lowering of the complex formation constants. In systems with a higher concentration of ethanol, the drug solubility was increased in opposition to the decreasing complex formation constants. According to this study, the type of CDs played a more important role on the solubility of Prx, and the use of ethanol as a co-solvent exhibited no synergistic effect on the improvement of Prx solubility. The Prx solubility was increased again due to the better solubility in ethanol.
本研究的目的是研究吡罗昔康（Prx）与各种环糊精（CDs）形成包合物以及以乙醇作为助溶剂时的溶解度。采用相溶解度法测定药物在二元和三元体系中的溶解度。结果表明，在药物溶解于乙醇 - 水混合物的体系中，药物溶解度随乙醇浓度的升高呈指数增加。药物在CDs（β - CD和γ - CD）水溶液中的相溶解度测量显示为A型图，而2,6 - 二甲基 - β - CD也显示为A型。无论CD类型如何，对于所有络合物都观察到乙醇作为助溶剂的去稳定作用，其结果是络合物形成常数降低。在乙醇浓度较高的体系中，尽管络合物形成常数降低，但药物溶解度却增加了。根据本研究，CDs的类型对Prx的溶解度起更重要的作用，并且使用乙醇作为助溶剂对改善Prx溶解度没有协同作用。由于Prx在乙醇中的溶解度更好，其溶解度再次增加。
