DEVELOPMENT OF MICROEMULSION FOR SOLUBILITY ENHANCEMENT OF ATORVASTATIN CALCIUMAbstract
Atorvastatin Calcium, competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway, thereby lowering cholesterol level in plasma of body. Oral bioavailability of Atorvastatin Calcium is very low (less than 4%), due to its poor water solubility. The aim of this investigation was to develop a microemulsion of Atorvastatin Calcium for enhancing its solubility, and its oral bioavailability. For this purpose, initially, solubility of Atorvastatin Calcium was determined in various vehicles. Oil, Surfactant and Cosurfactant were selected based on the solubility and HLB value. Pseudo-ternary phase diagrams were constructed to identify the microemulsion existing zone. Solubility study was also performed for optimization of formulation. The optimized microemulsion formulation was characterized for its % transmission, globule size, zeta potential, conductivity, % assay, and phase separation study. Globule size and zeta potential of the optimized microemulsion formulation were found to be 57.61 nm, and -19.4 mV, respectively. The viscosity and conductivity data indicated that the microemulsion was of the o/w type. Solubility of Atorvastatin Calcium was successfully enhanced via Isopropyl myristate microemulsion, compared with distilled water (pH = 7.4). 82.32% and 79.74 % of the drug content were found to be released within 8 h in the in-vitro and ex-vivo studies, respectively. Hence, by formulating into microemulsion, the solubility of Atorvastatin Calcium was found to be significantly enhanced.
Hemangini Rana*, Bhavdip Jesadiya and Surjyanarayan Mandal
Assistant Professor, Department of Pharmaceutics, L.B. Rao Institute of Pharmaceutical Education & Research, Bethak Road, Khambhat, Gujarat, India
02 April, 2013
06 May, 2013
26 July, 2013
01 August, 2013