Effect of hydrophilic polymer on complexing efficiency of cyclodextrins towards efavirenz-characterization and thermodynamic parameters

Abstract

The present work describes the effect of PVP on the complexation efficiency of cyclodextrins towards efavirenz, a poorly soluble antiretroviral agent imparting irritating sensation to buccal cavity. The phase solubility study indicates 1:1 stoichiometry for binary and ternary systems. DSC and XRPD revealed complete inclusion only in the lyophilized systems. The ternary systems were autoclaved before being lyophilized for the best results. Proton NMR suggests that the chlorobenzene part of benzoxazinone ring of the drug is involved in inclusion and was confirmed by 2D-COESY. The thermodynamic parameters, indicative of complexation efficiency were calculated calorimetrically by determining the interaction enthalpy of efavirenz with cyclodextrins in the presence and absence of PVP. The value of stability constants increased in the order β-CD < HP-β-CD < M-β-CD and is still higher in the presence of PVP illustrating the facilitation of the inclusion. Molar enthalpy of interaction of autoclaved solid formulation determined calorimetrically indicated stronger interaction for efavirenz:M-βCD-PVP system (−12.20 kJ/mol) which showed highest solubility and dissolution rate. The in vitro measurement of permeability showed a ten fold increase in the flux for the autoclaved formulation containing efavirenz-M-β-CD-PVP. In conclusion, encapsulation by cyclodextrins increases the solubility and suppresses the oral irritation of efavirenz. PVP further increases the complexation efficiency and decreases the bulk of cyclodextrins.