Arginine Complexes with Simvastatin: Apparent Solubility, In Vitro Dissolution and Solid State Characterization.
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.
Pharmaceutical and Life Sciences Core, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan. Malaysia.
Meor Mohd Redzuan Meor Mohd
MMRMM
Affandi
Pharmaceutical and Life Sciences Core, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan. Malaysia.
Minaketan
M
Tripathy
Pharmaceutical and Life Sciences Core, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan. Malaysia.
Abu Bakar Abdul
ABA
Majeed
D001120:Arginine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D033362:Powder Diffraction; D019821:Simvastatin / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D014867:Water / Q000737:chemistry
D014867:Water; D001120:Arginine; D019821:Simvastatin
Solubility; X-Ray powder defractometric; arginine complexes; dissolution; simvastatin; solid state