Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, 400019, India.
Drug Deliv Transl Res. 2016 Aug;6(4):380-91. doi: 10.1007/s13346-015-0271-x.
Atorvastatin calcium (AC) is a BCS class II drug which shows poor bioavailability due to inadequate dissolution. Solid dispersions present a promising option to enhance the solubility of poorly soluble drugs. Co-grinding with hydrophilic excipients is an easy and economical technique to improve the solubility of poorly soluble drugs and is free from usage of organic solvents. The aim of the present study was to explore novel carrier VBP-1 (organosulphur compound) for formulating a solid dispersion by using a simple, commercially viable co-grinding technique to enhance the dissolution of AC and to develop an oral formulation of the same. Composition of the solid dispersion was optimized based on the release profile in pH 1.2 buffer. The optimized solid dispersion was further characterized for flow properties, DSC, FTIR spectroscopy, XRD, contact angle, SEM studies and release profile in phosphate buffer pH 6.8. The developed solid dispersion gave similar release profile as the innovator formulation (Lipitor® tablets) in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed solid dispersion was formulated into hard gelatin capsules (size 3). The developed capsules were found to give similar release as the innovator formulation in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed capsules were found to be stable for a period of 6 months. Anti-hyperlipidemic efficacy studies in rats showed higher reduction in cholesterol and triglyceride levels by the developed capsules in comparison to pure AC. In conclusion, novel carrier VBP-1 was successfully employed to enhance the dissolution of AC using co-grinding technique.
阿托伐他汀钙（AC）是一种 BCS 类 II 药物，由于溶解不足，其生物利用度较差。固体分散体是提高难溶性药物溶解度的一种很有前途的选择。与亲水性赋形剂共研磨是一种提高难溶性药物溶解度的简单且经济的技术，并且无需使用有机溶剂。本研究的目的是探索新型载体 VBP-1（有机硫化合物），通过使用简单、商业可行的共研磨技术来制备固体分散体，以提高 AC 的溶解度，并开发相同的口服制剂。基于在 pH 1.2 缓冲液中的释放曲线来优化固体分散体的组成。进一步对优化的固体分散体进行了流动性、DSC、FTIR 光谱、XRD、接触角、SEM 研究以及在磷酸盐缓冲液 pH 6.8 中的释放曲线的特征研究。所开发的固体分散体在 pH 1.2 缓冲液和磷酸盐缓冲液 pH 6.8 中均具有与创新制剂（立普妥®片剂）相似的释放曲线。将所开发的固体分散体制成硬明胶胶囊（3 号）。在 pH 1.2 缓冲液和磷酸盐缓冲液 pH 6.8 中，所开发的胶囊均显示出与创新制剂相似的释放曲线。所开发的胶囊在 6 个月的时间内保持稳定。在大鼠中的抗高血脂药效学研究表明，与纯 AC 相比，所开发的胶囊能更有效地降低胆固醇和甘油三酯水平。总之，成功地使用新型载体 VBP-1 通过共研磨技术提高了 AC 的溶解度。
