一种新的阿魏酸-烟酰胺共晶,具有改善的溶解度和溶解性能。

A New Ferulic Acid-Nicotinamide Cocrystal With Improved Solubility and Dissolution Performance.

机构信息

Department of Pharmacy, Postgraduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal 59010-115, Brazil.

Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa 58051-970, Brazil.

出版信息

J Pharm Sci. 2020 Mar;109(3):1330-1337. doi: 10.1016/j.xphs.2019.12.002. Epub 2019 Dec 7.

Abstract

Among the various strategies for increasing aqueous solubility of pharmaceutical substances, cocrystals have been emerging as a promising alternative. The ferulic acid (FEA) is a molecule with limited aqueous solubility, but with an interesting pharmacological activity, highlighting its antitumor potential. This study presents the characterization and physicochemical properties of a new cocrystal based on FEA and nicotinamide (NIC). The FEA-NIC cocrystal was obtained by solvent evaporation technique and physicochemically characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance and scanning electron microscopy. The content determination and dissolution profile in different media were analyzed by high-performance liquid chromatography. The results obtained with the characterization techniques indicated the obtainment of an anhydrous cocrystal of FEA and NIC at a 1:1 molar ratio. The method was reproducible and obtained a high yield, of approximately 99%. In addition, a 70% increase in the FEA solubility in the cocrystal and a better dissolution performance than the physical mixture in pH 6.8 were achieved.

摘要

在提高药物物质水溶性的各种策略中,共晶已经成为一种很有前途的替代方法。阿魏酸(FEA)是一种水溶性有限的分子,但具有有趣的药理学活性,突出了其抗肿瘤潜力。本研究介绍了基于阿魏酸(FEA)和烟酰胺(NIC)的新型共晶的表征和物理化学性质。FEA-NIC 共晶通过溶剂蒸发技术获得,并通过差示扫描量热法、粉末 X 射线衍射、傅里叶变换红外光谱、固态核磁共振和扫描电子显微镜进行物理化学表征。通过高效液相色谱法分析了不同介质中的含量测定和溶解曲线。表征技术的结果表明,在 1:1 摩尔比下获得了阿魏酸和烟酰胺的无水共晶。该方法可重复,收率高,约为 99%。此外,在共晶中的 FEA 溶解度提高了 70%,在 pH6.8 时的溶解性能优于物理混合物。

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