Formulation Development and Evaluation of Nanocarrier for Increasing Bioavailability of Poorly Water Soluble Drugs

Abstract

In the present study the nanocarrier s were developed for the drugs namely rifabutin and azithromycin, by using the solvent diffusion evaporation method with minor modifications. The nanocarrier formulations were formulated and optimized using QbD technique. A Box-Behnken design (BBD) was employed for the systematic optimization of the identified variables. The drugs rifabutin and azithromycin were separately incorporated into lipidic nanocarrier with high efficiency. Developed nanocarrier formulations were characterized for their physicochemical characteristics and Stability studies. The in-vitro studies for the formulated nano-encapsulated containing drugs as detailed above showed that the nano-sized carriers of these drugs were developed with high % encapsulation efficiency. In vitro drug release studies show the slow and sustained release of the drugs. Cytotoxicity studies showed that an increase cell survival rate in MTT assay as compared to normal drugs. The haemolytic toxicity assay showed that % haemolysis was also significantly reduced when compared to plain drug, the haemolytic assay finding clearly indicate that the nano-formulation has a potential to be a carrier for the drug delivery with less toxicity score and with more efficacy in case of the both drugs i.e. rifabutin and azithromycin. The in-vivo study showed that the nanocarrier drug formulation has significant higher Tmax and Cmax plasma value with higher t1/2(h) values in comparison to plain drug in in case of the both drugs i.e. rifabutin and azithromycin, Moreover, the slow elimination rate (Kel) resulted in significant (Plt0.001) prolonged half-life (t1/2), which was many folds higher than the plain drug. These findings strongly advocated the possibility of reduction of dose and dosing frequency of both the drugs rifabutin and azithromycin separately with nano-lipoidal carrier. newlineThe multiple in-vitro and in-vivo studies revealed that the nanocarrier formulation for both the drugs rifabutin and azithromycin have succeeded to improve the delive