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Objective: To enhance solubility of efavirenz by using chitosan-graft-HPβCD copolymer synthesized by novel one pot technique. Methodology : Poor aqueous solubility and limited bioavailability is the major problem for more than 40% NEC (new chemical entities). Efavirenz (EFV), widely used non nucleoside reverse transcriptase inhibitor (NNRTI) belongs to BCS class II drug is having very poor intrinsic water solubility and limited oral bioavailability. Chitosan –graft-HPβCD (CS-g-HPβCD) copolymer was synthesized by tosylation of HPβCD followed by grafting on chitosan (CS) backbone. CS-g-HPβCD was prepared by varying CS: HPβCD weight ratios (1:1, 1:2, 1:3 and 1:4). The copolymer was characterized by FT-IR, NMR and DSC. The molecular weight of grafted copolymer was determined and copolymer was further evaluated for its solubility enhancement capability. Result: Tosylated HPβCD was grafted on CS backbone by simple one pot synthesis method. FT-IR, NMR and DSC results avowed the synthesis of grafted copolymer. The molecular weight of grafted polymer was greater than molecular weight of CS also support confirmation of HPβCD grafting on CS. The copolymer was found to tremendously enhance aqueous solubility of EFV (380 times the solubility of drug in water). These results conclusively demonstrated synthesis of grafted copolymer possessing good potential in the solubility enhancement of the poorly water soluble drug like EFV. Conclusion: Grafted copolymer is an excellent strategy to conquer the solubility issues of hydrophobic drugs like EFV owing to solubility enhancement capability and mucoadhesivity. Key words: Chitosan, Chitosan-g-HPβCD, Efavirenz, Hydroxypropyl-β- cyclodextrin, Grafting, Solubility enhancement.

Synthesis of Chitosan-Graft- HPβCD Copolymer by Novel One Pot Technique and its application for Solubility Enhancement of Efavirenz