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

[Display omitted] •Celecoxib (CLX) as a low water-soluble drug has a limited bioavailability.•Supercritical CO2 as an anti-solvent crystallization (SAS) were applied.•Box-Behnken design was used to optimize the effect parameters of the SAS.•The optimal SAS sample increased the solubility and dissolu...

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Veröffentlicht in:Chemical engineering research & design 2022-01, Vol.177, p.741-750
Hauptverfasser: Sadeghi, Fatemeh, Soleimanian, Zina, Hadizadeh, Farzin, Shirafkan, Azadeh, Kamali, Hossein, Afrasiabi Garekani, Hadi
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Sprache:eng
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Zusammenfassung:[Display omitted] •Celecoxib (CLX) as a low water-soluble drug has a limited bioavailability.•Supercritical CO2 as an anti-solvent crystallization (SAS) were applied.•Box-Behnken design was used to optimize the effect parameters of the SAS.•The optimal SAS sample increased the solubility and dissolution rate of CLX.•The SAS produced the sponge like particles with decreased crystallinity. 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.
ISSN:0263-8762
1744-3563
DOI:10.1016/j.cherd.2021.11.029