Affandi Meor Mohd Redzuan Meor Mohd, Tripathy Minaketan, Majeed Abu Bakar Abdul
Pharmaceutical and Life Sciences Core, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan. Malaysia.
Curr Drug Deliv. 2018;15(1):77-86. doi: 10.2174/1567201814666170320144259.
Categorized as a Biopharmaceutics Classification System (BCS) Class II drugs, statin exhibit low aqueous solubility and bioavailability thus presenting an obstacle and great challenge to formulation researchers. This paper describes a de novo approach to enhance the aqueous solubility of one of the most commonly prescribed statins i.e., simvastatin (SMV) by forming a complex (SMV-ARG) with cosolute arginine (ARG).
The complex has been characterized for its apparent solubility and in vitro dissolution. The solid state characterization has been carried out using Fourier Transform Infra-Red (FTIR) Spectroscopy, Elemental Analysis, X-Ray Powder Diffraction (XRD), Differential Scanning Calorimetry (DSC) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM).
Simvastatin-Arginine (SMV-ARG) complex exhibited massive solubility enhancement by 12,000 fold and significant improvement in both acidic and alkaline dissolution media. A conversion of coherent crystalline to non-coherent pattern, and certain extent of amorphization in SMV-ARG complex, fully justifies the enhanced solubility, and hence the dissolution profile.
The present study provides a significant evidence that ARG molecules are capable to form a complex with small molecules and increase their aqueous solubility which prove to be beneficial in drug formulation and development.
他汀类药物被归类为生物药剂学分类系统（BCS）II类药物，其水溶性和生物利用度较低，这给制剂研究人员带来了障碍和巨大挑战。本文描述了一种从头开始的方法，即通过与共溶质精氨酸（ARG）形成复合物（SMV-ARG）来提高最常用的他汀类药物之一辛伐他汀（SMV）的水溶性。
对该复合物的表观溶解度和体外溶出度进行了表征。使用傅里叶变换红外（FTIR）光谱、元素分析、X射线粉末衍射（XRD）、差示扫描量热法（DSC）分析、热重分析（TGA）和扫描电子显微镜（SEM）进行了固态表征。
辛伐他汀-精氨酸（SMV-ARG）复合物的溶解度大幅提高了12000倍，在酸性和碱性溶出介质中均有显著改善。SMV-ARG复合物中晶体从相干结晶转变为非相干模式，并出现一定程度的非晶化，充分证明了溶解度的提高以及溶出曲线的改善。
本研究提供了重要证据，表明ARG分子能够与小分子形成复合物并增加其水溶性，这在药物制剂和开发中被证明是有益的。
