Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling
This study investigates the co-amorphization of ketoconazole (KTZ) with fumaric acid (FA) and tartaric acid (TA) through co-milling, aiming to enhance the solubility, stability, and dissolution properties of this poorly water-soluble antifungal. Phase diagrams obtained via Hot Stage Microscopy (HSM)...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Penerbit Universiti Kebangsaan Malaysia
2025
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| Online Access: | http://journalarticle.ukm.my/25818/ http://journalarticle.ukm.my/25818/1/SME%2014.pdf |
| _version_ | 1848816458658742272 |
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| author | Indra, Indra Nurani, Rani Wulandari, Winda Trisna |
| author_facet | Indra, Indra Nurani, Rani Wulandari, Winda Trisna |
| author_sort | Indra, Indra |
| building | UKM Institutional Repository |
| collection | Online Access |
| description | This study investigates the co-amorphization of ketoconazole (KTZ) with fumaric acid (FA) and tartaric acid (TA) through co-milling, aiming to enhance the solubility, stability, and dissolution properties of this poorly water-soluble antifungal. Phase diagrams obtained via Hot Stage Microscopy (HSM) showed eutectic-like behavior at equimolar ratios for both KTZ-FA and KTZ-TA systems, with a more pronounced melting point depression in KTZ-FA, indicative of stronger molecular interactions fostering stable amorphous formation. Solid-state characterization using Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and Differential Scanning Calorimetry confirmed amorphization and showed significant hydrogen bonding in KTZ-FA. Further analyses with Thermogravimetric Analysis and Scanning Electron Microscopy demonstrated reduced thermal stability and particle size, accompanied by homogenous amorphous morphologies. Solubility and dissolution studies highlighted remarkable improvements: solubilities of KTZ-FA and KTZ-TA were 11.652 mg/mL and 8.750 mg/mL, respectively, compared to 0.060 mg/mL for pure KTZ. Dissolution profiles indicated superior performance of KTZ-FA at neutral pH, attributed to enhanced hydrogen bonding. Taken together, these findings position the co-amorphous KTZ–FA and KTZ–TA systems as promising candidates for developing rapid-acting oral antifungal dosage forms with improved bioavailability and patient compliance. |
| first_indexed | 2025-11-15T01:06:12Z |
| format | Article |
| id | oai:generic.eprints.org:25818 |
| institution | Universiti Kebangasaan Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T01:06:12Z |
| publishDate | 2025 |
| publisher | Penerbit Universiti Kebangsaan Malaysia |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | oai:generic.eprints.org:258182025-09-04T07:42:26Z http://journalarticle.ukm.my/25818/ Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling Indra, Indra Nurani, Rani Wulandari, Winda Trisna This study investigates the co-amorphization of ketoconazole (KTZ) with fumaric acid (FA) and tartaric acid (TA) through co-milling, aiming to enhance the solubility, stability, and dissolution properties of this poorly water-soluble antifungal. Phase diagrams obtained via Hot Stage Microscopy (HSM) showed eutectic-like behavior at equimolar ratios for both KTZ-FA and KTZ-TA systems, with a more pronounced melting point depression in KTZ-FA, indicative of stronger molecular interactions fostering stable amorphous formation. Solid-state characterization using Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and Differential Scanning Calorimetry confirmed amorphization and showed significant hydrogen bonding in KTZ-FA. Further analyses with Thermogravimetric Analysis and Scanning Electron Microscopy demonstrated reduced thermal stability and particle size, accompanied by homogenous amorphous morphologies. Solubility and dissolution studies highlighted remarkable improvements: solubilities of KTZ-FA and KTZ-TA were 11.652 mg/mL and 8.750 mg/mL, respectively, compared to 0.060 mg/mL for pure KTZ. Dissolution profiles indicated superior performance of KTZ-FA at neutral pH, attributed to enhanced hydrogen bonding. Taken together, these findings position the co-amorphous KTZ–FA and KTZ–TA systems as promising candidates for developing rapid-acting oral antifungal dosage forms with improved bioavailability and patient compliance. Penerbit Universiti Kebangsaan Malaysia 2025 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/25818/1/SME%2014.pdf Indra, Indra and Nurani, Rani and Wulandari, Winda Trisna (2025) Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling. Sains Malaysiana, 54 (6). pp. 1593-1604. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol54num6_2025/contentsVol54num6_2025.html |
| spellingShingle | Indra, Indra Nurani, Rani Wulandari, Winda Trisna Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling |
| title | Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling |
| title_full | Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling |
| title_fullStr | Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling |
| title_full_unstemmed | Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling |
| title_short | Enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling |
| title_sort | enhanced solubility and dissolution of ketoconazole through co-amorphization with fumaric and tartaric acids via co-milling |
| url | http://journalarticle.ukm.my/25818/ http://journalarticle.ukm.my/25818/ http://journalarticle.ukm.my/25818/1/SME%2014.pdf |