Comparison of static and dynamic sonication as process intensification for particle size reduction using a factorial design

Abstract

This article reports on particle engineering by a top-down method involving organic solvent-free acoustic cavitation as a wet-grinding procedure. The effects of static and dynamic sonication on particle size reduction methods were compared to each other. The most effective process parameters were determined by a factorial design plan for the particle size distribution of an important active pharmaceutical ingredient, meloxicam, as response factor after sonication. Samples sonicated with appropriate process parameters were dried and investigated. Scanning electron microscopy images showed that the sonication resulted in a rounded shape and micronized size of the particles. Differential scanning calorimetry and X-ray powder diffraction examinations revealed the crystalline structure of the produced meloxicam by both sonication methods. Fourier transform infrared spectroscopy demonstrated that no chemical degradation occurred. Static sonication is recommended primarily for particle size reduction in preclinical samples, where the amount of the drug candidate is very small (e.g. nasal formulation), while dynamic sonication may be suitable for wet-grinding of different active substances to prepare pre-suspension (e.g. micronization and nanonization).