Processing of ketoconazole-4-aminobenzoic acid cocrystals using dense CO2 as an antisolvent

•KET-PABA cocrystals were successfully produced by GAS.•Drug content in cocrystals produced by GAS was 77%, equivalent to 1:1 molar ratio.•KET in the cocrystals obtained from GAS could dissolve 47.5 ± 5.9% after 4 h.•KET-PABA cocrystal could dissolve 2.6 times faster than the unprocessed KET.

The aim of this work was to improve the dissolution rate of a poorly water-soluble antifungal drug, ketoconazole (KET), by forming cocrystal with 4-amino benzoic acid (PABA). Gas Anti-Solvent (GAS) technique with the use of dense carbon dioxide as an anti-solvent was applied for cocrystallization. The effects of KET to PABA molar ratio (1:2, 1:1 and 1:0.5), temperature (25-45 °C) and solvent type (methanol, ethanol, acetone and a solvent mixture of methanol and ethanol) on drug content and dissolution rate were investigated. It was found that the drug content of the produced cocrystal via GAS was approximately 77%, which was equivalent to 1:1 molar ratio, irrespective of the drug to coformer molar ratio used at the starting. Cocrystal synthesized by GAS using KET to PABA molar ratio of 1:2 in methanol at 25 °C exhibited the fastest dissolution rate compared to unprocessed drug, physical mixture and cocrystal prepared by slow evaporation.

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