Anti-solvent crystallization of celecoxib in the presence of PVP for enhancing the dissolution rate: comparison of water and supercritical CO2 as two antisolvents

Abstract For dissolution enhancement of celecoxib (CLX), an anti-solvent crystallization technique in the presence of polyvinylpyrrolidone (PVP) was applied by either water (WAS), a conventional method, or supercritical CO2 as anti-solvent (SAS). Box-Behnken design with the parameters of temperature (T), pressure (P), and time required to depressurize (td) was applied to examine the effect of variables in the SAS process. In the SAS process, maximum dissolution (81.7 % after 90 min) and saturation solubility (8.6 µg/mL) were obtained when the T, P, and td were 50 °C, 300 bar, and 20 min, respectively. Optimal SAS samples exhibited a higher dissolution rate compared to particles obtained by the WAS. The presence of PVP in the SAS sample increased the solubility of CLX by 2.7-fold in comparison to untreated CLX. The greater dissolution rate of the SAS sample could arise from the formation of sponge-like particles with increased porosity, crystallinity reduction, and increased CLX solubility.