ULTRASOUND ASSISTED COOLING CRYSTALLIZATION OF PARACETAMOL: EFFECT OF PROCESS PARAMETERS ON CRYSTAL YIELD, CRYSTAL SIZE AND OPTIMIZATION THROUGH BOX-BEHNKEN DESIGN

Abstract

The present study consists of ultrasound assisted cooling crystallization (USAC) of paracetamol. In this USAC study, the effect of various parameters such as pulsed ultrasound, amplitude, temperature, feed solution supersaturation, and crystallization time on the crystallized paracetamol yield and particle size was investigated. Further, the Box-Behnken experimental design (BBD) was utilized to conclude the most significant parameters affecting yield and crystal size. The optimum condition of BBD was found to be supersaturation level at 1.5, amplitude at 39.99 %, and sonication time at 19.47 min, and this condition, the yield of crystals was found to be 36.5 % and the crystal size of 10.793 μm as compared to raw paracetamol crystal size of 18.277 μm. Crystals were also determined
by Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), and Scanning Electron Microscopy (SEM). Accurate prismatic shaped morphology of crystallized paracetamol crystals was observed in the USAC process. From the dissolution study, the drug release profile revealed that the crystallized paracetamol released 80.189 % in just 55 min whereas raw paracetamol crystals needed 90 min to release 81.243 % for the 150 mg tablet formulation.