Abstract

Solubility Enhancement and Formulation of Nanoparticles of Efavirenz using Chitosan-Graft-HPßCD copolymer

Aarti Belgamwar, Research Scholar, Institute of Pharmaceutical Education and Research

The present study is focused on developing and exploring a novel method for solubility enhancement of water insoluble antiretroviral drug Efavirenz (EFV) by using chitosan –graft-HPßCD (CS-g-HPßCD) copolymer synthesized by simplified one pot reaction technique and further it was applied as carrier for formulation of nanoparticles. CS-g-HPßCD copolymer was synthesized by tosylation of HPßCD followed by grafting on CS backbone. The grafting was confirmed by FT-IR, NMR, DSC and elemental analysis. The copolymer has tremendously enhanced aqueous solubility of EFV (350 times than plain water). Efavirenz nanoparticles (EFV-NPs) were formulated by ionic gelation method using copolymer as a carrier. A two-level, two factor central composite design (CCD) was employed for formulations designing. Influence of polymer and drug concentration on particle size, zeta potential, percent drug content and encapsulation efficiency was studied. The results demonstrated that prepared nanoparticles were in size range of 198.7- 471.3 nm having zeta potential 5.19-17.2 mV with polydispersity index between 0.325-0.675. Percent drug content was found to be 4.12 -30 with percent entrapment efficiency of 31.33 - 62.41. These results suggest that, this copolymer may prove good carrier for nanoparticulate system of hydrophobic drugs like EFV to overcome solubility and dose related problem in HIV treatment. Key words: Chitosan, Hydroxypropyl-ß-cyclodextrin, nanoparticles, Efavirenz, graft copolymers.