Development and bioavailability studies of atorvastatin nanoemulsion

Abstract

Poor bioavailability by the oral route can be due to poor solubility, degradation in GI lumen, poor membrane permeation and presystemic elimination. Any of the approaches, which can alter these characteristics, should help in improving the bioavailability of the drugs. Atorvastatin is one of the most important hypolipidemic drug available today and circumventing the major problem of its poor bioavailability remains a bigger challenge of pharmaceutical scientists.The objective of the present study was to develop and characterize an optimal stable nanoemulsion formulation of atorvastatin (AT) with an aim to increase its bioavailability. The components selected for the nanoemulsion were of GRAS category as the safety is the major determining factor for the excipient selection. Thus, Safsol 218 and Oleic acid mixture was selected as the oil phase, surfactants namely Tween 20 and the co-surfactants, Carbitol were selected. Pseudo ternary phase diagrams were constructed using aqueous titration method. From phase diagram different concentrations of oil and surfactant, which formed nanoemulsions were selected based on the thermodynamic stability and dispersibility test. Optimized formulation was selected for in vivo study on the basis of higher drug release, optimum globule size, minimum polydispersity value, lower viscosity, and overall lower surfactant concentration and co-surfactant. The difference in t_max of nanoemulsion formulation was found to be significant (p<0.05) when compared to API drug suspension whereas the difference was insignificant (p>0.05) when compared to tablet. The difference in C_max of nanoemulsion was very significant (p<0.01) when compared with the tablet suspensions and API drug suspension. The relative bioavailability of nanoemulsion to that of conventional tablet suspensions was 356.32% whereas to that of API drug suspension was 559.86% respectively. Thus nanoemulsions could be used effectively to improve the bioavailability of poorly water soluble drugs to improve their bioavailability.