Department of Food and Medicines, Faculty of Pharmaceutical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais 37130-001, Brazil.
Institute of Chemistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais 37130-001, Brazil.
J Pharm Sci. 2019 Jul;108(7):2458-2464. doi: 10.1016/j.xphs.2019.03.001. Epub 2019 Mar 7.
Spironolactone (SPR) is a poorly water-soluble drug widely used for the treatment of various diseases. The objective of this study was to carry out the preparation and solid-state characterization of SPR 1/3 hydrate. The solid form was generated by an unreported recrystallization process in acetone and characterized for the first time by a combination of X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), equilibrium solubility, and an accelerated stability study. XRD, DSC, and TGA studies revealed that SPR 1/3 hydrated converts completely to form II after heating to 180°C. Solubility studies at 37°C showed that SPR 1/3 hydrate was statistically less soluble than SPR form II in all tested media and that SPR form II partially converts to SPR 1/3 hydrate in aqueous media. Accelerated stability studies demonstrated that both forms were physically and chemically stable up to 6 months (40°C/75% RH). We concluded that contamination of SPR 1/3 hydrate in SPR raw materials is undesirable. Taking this into account we recommend its polymorphic monitoring either in active pharmaceutical ingredients or commercial tablets by solid-state identification/quantification methods (XRD, DSC, TGA, and FTIR). Of these, XRD proved to be the most conclusive and accurate.
螺内酯（SPR）是一种水溶性较差的药物，广泛用于治疗各种疾病。本研究的目的是制备并对 SPR 1/3 水合物进行固态特性表征。该固体形式是通过在丙酮中未经报道的重结晶过程产生的，并首次通过 X 射线粉末衍射（XRD）、差示扫描量热法（DSC）、热重分析（TGA）、傅里叶变换红外光谱（FTIR）、平衡溶解度和加速稳定性研究进行了表征。XRD、DSC 和 TGA 研究表明，SPR 1/3 水合物在加热至 180°C 后完全转化为 II 型。在 37°C 下的溶解度研究表明，在所有测试的介质中，SPR 1/3 水合物的溶解度明显低于 SPR II 型，并且 SPR II 型在水介质中部分转化为 SPR 1/3 水合物。加速稳定性研究表明，两种形式在 40°C/75% RH 下稳定 6 个月。我们得出结论，SPR 原料药中 SPR 1/3 水合物的污染是不理想的。考虑到这一点，我们建议通过固态鉴定/定量方法（XRD、DSC、TGA 和 FTIR）对原料药或市售片剂中的其多晶型进行监测。其中，XRD 被证明是最具结论性和准确性的方法。
