Faculty of Pharmaceutical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, 37130-001, Brazil.
São Carlos Institute of Physics, University of São Paulo (IFSC-USP), São Carlos, São Paulo, 13566-590, Brazil.
J Pharm Sci. 2024 Nov;113(11):3297-3303. doi: 10.1016/j.xphs.2024.08.025. Epub 2024 Aug 29.
Ciprofibrate (CIP) is an active pharmaceutical ingredient (API) classified as class II on the basis of biopharmaceutical classification system (BCS), what indicates that it has low solubility in aqueous solvents. The use of API salts has attracted attention due to their improvements in solubility, tolerability, higher rate and extent of absorption, and faster onset of the therapeutic effect. In this work, a new crystalline CIP monohydrated calcium salt (Ca(CIP).HO) was successfully obtained and its crystal structure determined by single crystal X-ray diffraction analysis (SCXRD). Additionally, Ca(CIP).HO was widely characterized by powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and submitted to solubility, intrinsic dissolution and accelerated stability studies. Ca(CIP).HO exhibited higher solubility and dissolution rate than CIP-free form and was stable up to 6 months at 40 °C (75 %RH). Therefore, Ca(CIP).HO may be a viable alternative for use in solid dosage forms.
氯贝丁酸（CIP）是一种基于生物药剂学分类系统（BCS）被归为 II 类的活性药物成分（API），这表明它在水性溶剂中的溶解度较低。API 盐的使用引起了人们的关注，因为它们可以提高溶解度、耐受性、更高的吸收率和吸收程度、以及更快的治疗效果起效时间。在这项工作中，成功获得了一种新的结晶 CIP 单水合钙盐（Ca(CIP).HO），并通过单晶 X 射线衍射分析（SCXRD）确定了其晶体结构。此外，通过粉末 X 射线衍射（PXRD）、傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）、热重分析（TGA）对 Ca(CIP).HO 进行了广泛的表征，并进行了溶解度、内在溶解和加速稳定性研究。Ca(CIP).HO 表现出比无 CIP 游离形式更高的溶解度和溶解速率，并且在 40°C（75%RH）下稳定长达 6 个月。因此，Ca(CIP).HO 可能是用于固体制剂的一种可行替代品。
