LOW ENERGY LIPID NANOEMULSION SYSTEM FOR IMPROVED BIOAVAILABILITY OF SOME POORLY SOLUBLE DURGS A MODIFIED FORMULATION APPROACH

Abstract

Nanoemulsion preparation was optimized initially by performing solubility study of the drugs atorvastatin, fenofibrate and olanzapine in different oils. From the solubility studies, the oil in which the drug showed maximum solubility is oleic acid for atorvastatin and capryol 90 for fenofibrate and olanzapine. The fate of drug in GIT was estimated by in vitro lipolysis model.Lipoanalysis studies indicated that the lipid phase is suitable for nanoemulsion formulation of respective drugs. The composition of NE was optimized using pseudoternary phase diagram study. The droplet size, PDI, zeta potential, viscosity, refractive index, % transmission and conductivity of the selected formulations were measured. The formulations with formulation code 8 with 25% oil (labrafac lipophile) solubulized by 32% ScoS and formulation code 16.25% oil (capryol 90) solubilized by 43.75% ScoS were selected for drug incorporation and in vitro and in vivo studies. The in vitro drug release from SNEDDS formulation for all the 3 drugs were extremely significant (pandlt; 0.001) in comparison to the marketed formulation and pure drug suspension. A maximum release of 99.54%, 68.30% and 20.43% for atorvastatin, 99.64% 64.20% and 19.33% for fenofibrate and 99.34%, 62.98% and 21.43% for olanzapine was observed with the SNEDDS, marketed formulation and pure drug suspension respectively. In in vivo studies the SNEDDS formulation was found to release maximum concentration of drug by 2hrs. While marketed formulation and pure drug suspension was found to release maximumamount of drug by 6 h, 8h, 2h, 4h and 4h, 6h for atorvastatin, fenofibrate and olanzapine respectively. In in vivo lymphatic absorption study, maximum lymphatic concentration of drugs was found to be in a similar fashion as that of the in vivo plasma absorption studies. The increasein bioavailability for SNEDDS for the drugs is evident from the lymphatic absorption study which is well supported by the pharmacokinetic parameters and in vivo plasma concentration profile.