Abstract
Supercritical carbon dioxide (scCO2) induces polymorphism in pharmaceutical drugs. However, it is unclear whether polymorphism is induced by the CO2 antisolvent effect or simply by the spray-drying step involved in the scCO2 antisolvent processes. Herein, this effect is clarified by using supercritical enhanced atomization techniques assisted with scCO2 and scN2 and three drugs (indomethacin (IND), carbamazepine (CBZ), and theophylline (TPL)) that have already exhibited polymorphism when processed by classical supercritical antisolvent (SAS) processing. Polymorphs were obtained by supercritical enhanced atomization (SEA) using either CO2 or N2 revealing that polymorphism was induced by atomization in all cases except for TPL, which was very sensitive to the CO2 antisolvent action. The TPL polymorph was produced by the atomization of supercritical antisolvent induced suspensions (ASAIS) process, which enables SAS to be performed in standard (atmospheric pressure) spray dryers. A computational fluid dynamic...
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