Formulation, optimization and evaluation of pellets loaded glipizide co amorphous mixture using central composite design to enhance solubility

The objective of this study was to prepare a co-amorphous blend of BCS class II drug, glipizide (GPZ), using arginine (ARG) as co former. The co-amorphous GPZ-ARG mixtures (molar ratios 1:1, 1:2 and 2:1) were prepared by mechanical activation (ball milling) with different milling times. The obtained mixtures were characterized with respect to their thermal properties, possible molecular interactions, dissolution properties and physical stability and compared to the behaviour of pure crystalline form. Solid-state characterization of mixture revealed amorphization of GPZ after 90 min. of ball milling. GPZ-ARG co amorphous mixture (1:2) upon ball milling for 90 min. exhibited maximum solubility (3876.8 μg/ml) compared to pure drug (300.89 μg/ml). The resulting best co amorphous blend was incorporated into pellets which were prepared by extrusion spheronisation technique. The parameters related to process of pelletisation and product related parameters were optimized by using 4-factor, 5-level Central Composite Design. The pellets containing co amorphous blend, prepared by using optimal parameter settings, showed 95.67% Drug Release in 120 min. (F23). The co-amorphous mixture and the optimized formulation were found to be stable when subjected to stability study as per ICH guideline. It was concluded that co amorphous is a promising approach to overcome the solubility constraint of Glipizide which would be helpful in better management of the disease.