Application of Box–Behnken Design to Investigate the Effect of Process Parameters on the Microparticle Production of Ethenzamide through the Rapid Expansion of the Supercritical Solutions Process

In this study, the rapid expansion of the supercritical solutions (RESS) process was used to produce microparticles of a commonly used anti-inflammatory drug, ethenzamide. The effects of process parameters in RESS including the extraction temperature, pre-expansion temperature, and post-expansion temperature were investigated using the Box–Behnken design. According to the results of the analysis of variance (ANOVA), the effect of pre-expansion temperature is the most significant parameter on the mean size of RESS-produced ethenzamide. A higher pre-expansion temperature benefits the production of smaller crystals. In addition, a quadratic effect of the post-expansion temperature was also identified. Through RESS, ethenzamide microparticles with a mean size of 1.6 μm were successfully produced. The solid-state properties including the crystal habit, crystal form, thermal behavior, and spectrometric property were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectrometer (FTIR), differential scanning calorimeter (DSC), and powder X-ray diffraction (PXRD). These analytical results show that the rod-like crystals were generated through RESS, and the crystal form, thermal behavior, and spectrometric property of RESS-produced crystals are consistent with the unprocessed ethenzamide.

Trends on the Rapid Expansion of Supercritical Solutions Process Applied to Food and Non-food Industries

Background: The supercritical fluids applied to particle engineering over the last years have received growing interest from the food and non-food industries, in terms of processing, packaging, and preservation of several products. The rapid expansion of supercritical solutions (RESS) process has been recently reported as an efficient technique for the production of free-solvent particles with controlled morphology and size distribution. Objective: In this review, we report technological aspects of the application of the RESS process applied to the food and non-food industry, considering recent data and patent survey registered in literature. Methods: The effect of process parameters cosolvent addition, temperature, pressure, nozzle size among others, during RESS on the size, structure and morphology of the resulted particles, and the main differences about recent patented RESS processes are reviewed. Results: Most of the experimental works intend to optimize their processes through investigation of process parameters. Conclusion: RESS is a feasible alternative for the production of particles with a high yield of bioactive constituents of interest to the food industry. On the other hand, patents developed using this type of process for food products are very scarce, less attention being given to the potential of this technique to develop particles from plant extracts with bioactive substances.