Improved dissolution of ketoconazole by coprecipitation with nicotinamide using gas anti-solvent process
Issued Date
2024-01-01
Resource Type
ISSN
25868195
eISSN
25868470
Scopus ID
2-s2.0-85196053360
Journal Title
Pharmaceutical Sciences Asia
Volume
51
Issue
2
Start Page
94
End Page
105
Rights Holder(s)
SCOPUS
Bibliographic Citation
Pharmaceutical Sciences Asia Vol.51 No.2 (2024) , 94-105
Suggested Citation
Juengwongsa C., Charoenchaitrakool M., Charoenthai N., Puttipipatkhachorn S. Improved dissolution of ketoconazole by coprecipitation with nicotinamide using gas anti-solvent process. Pharmaceutical Sciences Asia Vol.51 No.2 (2024) , 94-105. 105. doi:10.29090/psa.2024.02.24.1491 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98908
Title
Improved dissolution of ketoconazole by coprecipitation with nicotinamide using gas anti-solvent process
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
The gas anti-solvent (GAS) process utilizing compressed carbon dioxide as an anti-solvent was applied to prepare coprecipitated particles between ketoconazole (KET), a poorly water-soluble drug substance, and nicotinamide (NIC), a water-soluble carrier. KET-NIC solid dispersion was also prepared by solvent evaporation and compared with the coprecipitated particles obtained from GAS process. DSC results indicated that KET formed eutectic with NIC at a weight ratio of 7:3. The results showed that the KET-NIC coprecipitated particles prepared by the GAS process, at an initial weight ratio of 1:1.5 in ethanolic solution, had suitable particle morphology and exhibited a remarkably higher dissolution than solid dispersion, physical mixture, and unprocessed KET. The formation of a simple eutectic mixture between KET and NIC in the coprecipitates prepared by both processes was confirmed by DSC, FTIR spectroscopy and powder X-ray diffraction. The enhanced dissolution of the GAS coprecipitated particles might be attributed to the eutectic formation, the improved wettability and hydrophilic microenvironment by the water-soluble carrier, the lower crystallinity, and the smaller size of the drug crystals.