Background: 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).
Methods: 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).
Results: 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.
Conclusion: 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.