Mura P, Faucci M T, Bettinetti G P
Dipartimento di Scienze Farmaceutiche, Via G. Capponi 9, 50121, Firenze, Italy.
Eur J Pharm Sci. 2001 May;13(2):187-94. doi: 10.1016/s0928-0987(01)00093-8.
The combined effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) and polyvinylpyrrolidone (PVP) on the solubility of naproxen (NAP) was studied. Phase-solubility analysis at different temperatures was used to investigate interactions in aqueous solution between NAP and the carriers, either alone or in combination. Equimolar NAP-HPbetaCD solid systems, in the presence or the absence of 15% (w/w) PVP, were prepared by cogrinding, kneading, coevaporation or freeze-drying, and characterized by differential scanning calorimetry, X-ray powder diffraction analysis, infrared spectroscopy and dissolution rates. The combined use of PVP and HPbetaCD resulted in a synergistic increasing effect of the aqueous solubility of NAP (120 times that of the pure drug). The phenomenon was interpreted in terms of the strongest complexation capacity of HPbetaCD towards NAP, which was reflected by an about 65% increase in the apparent stability constant of the NAP-HPbetaCD complex in the presence of only 0.1% (w/v) PVP. Variations in thermodynamic parameters accounted for a PVP role in the formation of a NAP-HPbetaCD-PVP ternary complex. The positive effect of PVP also reflected on NAP dissolution rates from solid preparations, because all ternary systems, with the exception of physical mixtures, dissolved faster than the corresponding NAP-HPbetaCD binary systems. The results of solid state studies accounted for the occurrence of mechanically- and/or thermally-induced stronger interactions in ternary than in binary systems, that in some cases led to a complete loss of NAP crystallinity.
研究了羟丙基-β-环糊精（HPβCD）和聚乙烯吡咯烷酮（PVP）对萘普生（NAP）溶解度的联合作用。采用不同温度下的相溶解度分析来研究NAP与载体单独或联合在水溶液中的相互作用。通过共研磨、捏合、共蒸发或冷冻干燥制备了等摩尔的NAP-HPβCD固体体系，有无15%（w/w）PVP存在，并用差示扫描量热法、X射线粉末衍射分析、红外光谱和溶出速率进行表征。PVP和HPβCD联合使用导致NAP的水溶性有协同增加作用（是纯药物的120倍）。该现象可从HPβCD对NAP最强的络合能力来解释，这在仅存在0.1%（w/v）PVP时NAP-HPβCD络合物的表观稳定常数增加约65%中得到体现。热力学参数的变化说明了PVP在形成NAP-HPβCD-PVP三元络合物中的作用。PVP的积极作用也反映在固体制剂中NAP的溶出速率上，因为除物理混合物外，所有三元体系的溶解速度都比相应的NAP-HPβCD二元体系快。固态研究结果说明了三元体系中比二元体系发生了更强的机械和/或热诱导相互作用，在某些情况下导致NAP结晶度完全丧失。
