Combination Drug Product of Amorphous Solid Dispersion Show Extended Supersaturation and Enhanced Dissolution

Investigation on multidrug formulations is increasing, because of enhanced efficacy and patient compliance. The two antiparasitic drugs Albendazole (ABZ) and mebendazole (MBZ) combination is well reported in the clinical research. However, ABZ-MBZ drug combination do not progressed well due to in vivo drug-drug interaction of precipitation of either drug leading to sub-therapeutic concentration in systemic circulation. Herein, we studied the effect of various cellulosic polymers on the supersaturation behaviour of ABZ and MBZ in combination. We screened a large group of cellulosic polymers and selected HPMCAS on the basis of supersaturation behaviour, drug-polymer solubility, and drug particle size. An amorphous solid dispersion was developed comprising ABZ-MBZ and HPMCAS. Drug amorphization was confirmed using thermal and crystallographic technique. In kinetic solubility, the ternary ASD enhanced the solubility of ABZ/MBZ by 1.88/3.52-fold (pH 1.2), 146.08/201.38-fold (pH 6.8) and 182.47/50.38-fold (water) as compared to crystalline ABZ and MBZ. In vitro release study supports kinetic solubility data as in ternary ASD the fraction drug release of ABZ/MBZ was increased by 2.22/2.55-fold (pH 1.2), 22.82/25.98-fold (pH 6.8) and 18.5/12-fold (water) in comparison to crystalline drugs. AUC^0-120 min displayed significant enhancement in drug solubility with ternary ASD.