Analysis of niflumic acid prepared by rapid microwave-assisted evaporation

Abstract

Evaporative crystallization is widely applied in several industrial processes, including the pharmaceutical industry. Microwave irradiation can significantly speed up solvent evaporation in these crystallization processes, resulting in reduced particle size due to rapid crystallization. A single-mode microwave setup was used for evaporative crystallization of the model active pharmaceutical ingredient, niflumic acid, and the polymer, polyvinylpirrolidone (PVP). Production of crystals by microwave irradiation offers a modern way for drug formulation, and by reducing the particle size the dissolution rate and bioavailability of the active pharmaceutical ingredient can be enhanced. In this study, a 2.5-fold increase in the dissolution rate of the produced niflumic acid crystals was observed compared to the dissolution rate of the original drug in 120min. When niflumic acid was produced together with the PVP in the microwave system, an amorphous solid dispersion was created with particles in the nano-size range, which showed a 5-fold increase in dissolution rate in 120min compared to the dissolution of the crystalline niflumic acid samples created by the microwave irradiation in the absence of PVP.

Keywords: Amorphous solid dispersion; Evaporative crystallization; Microwave; Niflumic acid; Physico-chemical analysis.