Purpose: The purpose of the study was formulation development, optimization and evaluation
of a Self-Emulsifying Drug Delivery System (SEDDS) of Simvastatin (SIM) for improvement in
dissolution and bioavailability of SIM. Solubility enhancement of Biopharmaceutical Classification
System (BCS) Class-II drugs is a burning topic and attracting various publications and patents regarding
different strategies employed for improvement of dissolution viz., USOO5340591A (Solid dispersion),
US005472954A, US005646131A (complexation), USOO5858410A (Nanosuspensions),
USOO5874029A (micronization) US2008.00095O2A1 (Solid composites), US2008O146640A1 (Prodrug)
US 2009001 1009 A1 (nanocapsules), etc.
Methods: SEDDS was prepared on the basis of solubility studies employing Capmul MCM EP as lipid
and Cremophor ELP as surfactant. Box-Behnken design was implemented for optimization by using
lipid concentration, surfactant concentration and mixing time as dependent variables and their impact
was observed on particle size, poly dispersity index (PDI) and drug released in 15min. Optimized formulation
was evaluated for particle size, PDI, zeta potential, emulsification time, transmittance, invitro
drug release and in situ Single-Pass Intestinal Perfusion (SPIP) studies.
Results: For optimized formulation, OF1 value of particle size, PDI, zeta potential, emulsification
time, transmittance and percent in-vitro release were 162±14.32nm, 0.19±0.01, -22.3 ±1.1mV, 93±3.11
sec, 99.45±4.35 % and 99.43± 5.6 % in 30 min respectively. In-situ SPIP studies were performed on
Wistar rats and the value of predicted fraction absorbed for humans was found to be 0.98.
Conclusion: SIM SEDDS was successfully developed and evaluated for in-vitro & in-vivo parameters.
All the evaluated parameters were in tolerable limits. In vitro release studies from optimized formulation,
OF1, exhibited maximum drug release when compared to SIM API and marketed preparation.
Moreover, the predicted value of fraction absorbed (Fa) in humans by in-situ SPIP method was also in
agreement with in-vitro dissolution studies thus, confirming SEDDS as a suitable drug delivery system
for solubility enhancement of SIM.