Improved oral delivery of clonazepam through liquisolid powder compact formulations: In-vitro and ex-vivo characterization

Abstract

The liquisolid powder compacts (LSPCs) proved to be the potential solubility improvement strategy for efficient oral delivery of BCS class II and IV drugs. Henceforth, an attempt was made to improve the oral delivery of BCS class II drug clonazepam (CLZ) by formulating into a novel LSPCs. Solubility studies were conducted in different liquid vehicles, namely propylene glycol, span 20 and span 80. The LSPCs were formulated using propylene glycol as non volatile solvent. The effect of different formulation variables on LSPCs performance was evaluated using 32 factorial design. The selected independent variables were % of clonazepam in propylene glycol (X1) and % of sodium starch glycolate (X2) and dependent variables were disintegration time (YDT) and % cumulative drug release at 15th minute (YQ15). LSPCs of CLZ formulated with propylene glycol at optimum drug concentration produced high dissolution profile with acceptable tablet properties. Fourier transform infra-red spectroscopy (FTIR) studies revealed that there was no interaction between drug and polymers, differential scanning calorimetry (DSC) and X-Ray Diffraction (XRD) indicated conversion of crystalline to amorphous form of the CLZ. Further the permeation studies carried out in isolated rat intestine revealed that potential of LSPCs for enhanced permeation of CLZ across rat intestinal barrier. The increase in permeation of clonazepam from LSPCs formulation across rat intestine suggests the potential of LSPC formulation for improved oral delivery of CLZ.