Abstract
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.
Highlights
Microparticle production is a strategy used in the pharmaceutical industry to enhance the dissolution profile and improve the bioavailability of poorly water-soluble substances, especially for the biopharmaceutics classification system’s (BCS) class II and IV active pharmaceutical ingredients [1,2,3]
According to the rapid expansion of supercritical solutions (RESS) studies reported in the literature [10,11,12,13,14], the solid-state property of generated microparticles can be efficiently manipulated by process parameters such as the extraction temperature, extraction pressure, pre-expansion temperature, post-expansion temperature, nozzle design, and spraying distance
Regarding the effect of extraction temperature, a higher extraction temperature is preferable for producing smaller ethenzamide crystals
Summary
Microparticle production is a strategy used in the pharmaceutical industry to enhance the dissolution profile and improve the bioavailability of poorly water-soluble substances, especially for the biopharmaceutics classification system’s (BCS) class II and IV active pharmaceutical ingredients [1,2,3]. According to the role of the supercritical fluid used, different processes such as the rapid expansion of supercritical solutions (RESS), supercritical antisolvent (SAS), particles from gas-saturated solutions (PGSS), and supercritical-assisted atomization (SAA) were proposed in the literature [8,9]. Among these techniques, the rapid expansion of supercritical solutions (RESS) is an organic solvent-free process, beneficial in the particle formation of pharmaceutical solids. RESS has been successfully adopted for producing microparticles of pharmaceutical compounds such as olanzapine, mefenamic acid, nabumetone, paracetamol, tolbutamide, lonidamine, vanillin, and coumarin [10,11,12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
