Title:Quality Based Design Approach for Improving Oral Bioavailability of Valsartan Loaded Smedds And Study of Impact of Lipolysis on the Drug Diffusion
VOLUME: 8 ISSUE: 2
Author(s):Ravinder Verma, Vineet Mittal and Deepak Kaushik*
Affiliation:Department of Pharmaceutical Sciences, Maharshi Dayanand University. Rohtak, Department of Pharmaceutical Sciences, Maharshi Dayanand University. Rohtak, Department of Pharmaceutical Sciences, Maharshi Dayanand University. Rohtak
Keywords:SMEDDS, BCS, bioavailability, lipolysis, in vitro dissolution, D-optimal mixture design, fasted state stimulated
intestinal fluids media (FaSSIF).
Abstract:Background and Objective: In the present investigation, we have developed, optimized and
evaluated a self-micro emulsifying drug delivery system (SMEDDS) of an anti-hypertensive drug valsartan.
The objective of the study was to enhance dissolution rate, solubility and oral bioavailability of
valsartan which is BCS-II class drug.
Methods: Saturation solubility studies and emulsification tests were performed for selection of a suitable
combination of oil, surfactant and co-surfactant. Pseudo-ternary phase diagram was constructed to
estimate microemulsion region for selection of a required range of oil, surfactant and co-surfactant. Doptimal
mixture design was utilized to optimize the concentration of various components used in the
SMEDDS formulation and to analyze their effect on in vitro percent drug release and globule size. The
effect of lipolysis on the rate of drug release from optimized SMEDDS formulation was calculated using
in vitro lipolysis model.
Result: The valsartan loaded SMEDDS formulation (F-14) containing 10% Capmul MCM PG 8 (oil),
40% Tween 20 (surfactant) and 50% Transcutol P (co-surfactant) was found to be optimized formulation
with smallest globule size of 72.92 nm and significantly superior dissolution rate of valsartan in
comparison to the pure drug. No major effect of lipolysis was observed on the diffusion rate of the
drug from optimized SMEDDS formulation.
Conclusion: Valsartan loaded SMEDDS formulation was successfully developed by using D-optimal
mixture design that could potentially be used for improving the solubility, dissolution rate and
bioavailability of Biopharmaceutical Classification System (BCS) class-II drugs.