Cationic solid self micro emulsifying drug delivery system (SSMED) of losartan: Formulation development, characterization and in vivo evaluation

Abstract

The objective of the study was to develop solid self micro emulsifying drug delivery system (SSMED) for enhancement of oral bioavailability of losartan (LOS). Solubility of LOS in various vehicles was determined. Micro emulsion region was identified by constructing phase diagram containing surfactant: co-surfactant mixture (1:1 and 2:1), oil and water. Formulations were initially checked for droplet size upon addition to water. The formulations, which resulted in <200 nm size were further evaluated for self micro emulsification time, phase separation, effect of dilution and pH on droplet size, freeze-thaw stability. The optimized formulation (SMEDDS-C2) was positively charged and contained Capmul MCM 24%; Cremophor EL 37.5%; Transcutol P 37.5% and 1% stearyl amine and had an average particle size 142.51 ± 3.46 nm, zeta potential of +16.66 ± 0.46 mV. The SSMEDs were prepared by adsorption on 4 different carriers. Based on micromeritics, SSMED containing neusilin US2 (SSMED-N) was selected, characterized by DSC, XRD, SEM studies and in vitro dissolution. The in vitro release from liquid SMEDDS and SSMED-N was found to be significantly higher than LOS. The relative bioavailability of cationic SSMED-N in wistar rats was 2.82 times more than a drug suspension and stable for 3 months at room temperature (RT).