Acta Pharm. 57 (2007) 111-122

full paper

Short communication

Formulation of a self-emulsifying system for oral delivery of simvastatin: In vitro and in vivo evaluation

PRADEEP PATIL¹, VANDANA PATIL² and ANANT PARADKAR^1*

arparadkar@rediffmail.com

¹Department of Pharmaceutics, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Erandwane, Pune-411 038, Maharashtra State, India

²Department of Environmental Sciences, University of Pune, Ganeshkhind, Pune-411 007, Maharashtra State, India

Accepted November 2, 2006

The objective of the present work was to formulate a self-emulsifying drug delivery system (SEDDS) for simvastatin, which is widely used in the treatment of hypercholesterolemia and dyslipidemia as an adjunct to diet. Simvastatin SEDDS were formulated using a 1:1 (V/V) mixture of diesters of caprylic/capric acids and polyglycolyzed glycerides with varying concentrations of polyoxy 35 castor oil and C8/C10 mono-/diglycerides. The developed SEDDS were evaluated for turbidimetry, droplet size analysis, drug content and in vitro diffusion profiles. In vivo performance of the optimized formulation was evaluated in rats using pharmacodynamic marker parameters like plasma total cholesterol (CH), triglycerides (TG) and high-density lipoprotein (HDL-CH) for 21 days. SEDDS containing 9.1% (m/m) simvastatin and 23%, (m/m) of each excipient showed minimum mean droplet size (124 nm) and optimal drug diffusion. This test formulation showed significant reduction in plasma CH and TG (around 5-fold and 4-fold, respectively), while HDL-CH concentration was markedly higher (2-fold) compared a reference simvastatin suspension formulation after oral administration for 21 days of study. Test formulation has shown enhanced pharmacodynamic performance compared to reference formulation in rats. The study illustrated the potential of simvastatin SEDDS for oral administration and its biopharmaceutic performance.

Keywords: simvastatin, SEDDS, pharmacodynamics, oral administration, plasma lipids