Spherical agglomeration to improve dissolution and micromeritic properties of an anticancer drug, Bicalutamide

Abstract

Bicalutamide (BCT), an anticancer drug, suffers from dissolution rate limited bioavailability and poor micromeritic properties. Spherical crystallization involves the formation of spherical agglomerates with enhanced dissolution properties, obviating the need for further granulation process. The present investigation was focused on spherical agglomeration of BCT by quasi-emulsion solvent diffusion method. All the responses were subjected to principal component analysis to scrutinize the critical attributes. Further for optimization, X1; influence of phase ratio, X2; amount of PEG 6000 and X3; stirring speed on critical dependent variables was studied by employing the Box-Behnken experimental design. The agglomerates exhibited better flow properties, higher bulk density, and improved compressibility compared to pure powder drug. In-vitro release studies revealed enhancement of dissolution properties of poorly soluble BCT. Characterization studies carried out by differential scanning calorimeter and powder X-ray diffractometer revealed crystallinity of drug with decreased intensity in the formulation. Scanning electron microscopy showed spherical shape agglomerates of BCT. The residual solvents were largely below the permitted limits. Spherical agglomerates demonstrated enhanced dissolution properties on account of reduced particle size and partial conversion into amorphous form. Thus, spherical agglomerates of BCT seem to be a promising approach to ameliorate the dissolution properties which might thereby improve its bioavailability.