Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering
To improve the solubility and dissolution rate of the BCS class II drug ketoconazole, five novel solid forms in 1:1 stoichiometry were obtained upon liquid-assisted grinding, slurry, and slow evaporation methods in the presence of coformers, namely, glutaric, vanillic, 2,6-dihydroxybenzoic, protocat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1349 |
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| author | Hongmei Yu Li Zhang Meiju Liu Dezhi Yang Guorong He Baoxi Zhang Ningbo Gong Yang Lu Guanhua Du |
| author_facet | Hongmei Yu Li Zhang Meiju Liu Dezhi Yang Guorong He Baoxi Zhang Ningbo Gong Yang Lu Guanhua Du |
| author_sort | Hongmei Yu |
| collection | DOAJ |
| description | To improve the solubility and dissolution rate of the BCS class II drug ketoconazole, five novel solid forms in 1:1 stoichiometry were obtained upon liquid-assisted grinding, slurry, and slow evaporation methods in the presence of coformers, namely, glutaric, vanillic, 2,6-dihydroxybenzoic, protocatechuic, and 3,5-dinitrobenzoic acids. Single-crystal X-ray diffraction analysis revealed that the hydroxyl/carboxylic acid. . .N-imidazole motif acts as the dominant supramolecular interaction in the obtained solid forms. The solubility of ketoconazole in distilled water significantly increased from 1.2 to 2165.6, 321.6, 139.1, 386.3, and 191.7 μg mL<sup>−1</sup> in the synthesized multi-component forms with glutaric, vanillic, 2,6-dihydroxybenzoic, protocatechuic, and 3,5-dinitrobenzoic acid, respectively. In particular, the cocrystal form with glutaric acid showed an 1800-fold solubility increase in water concerning ketoconazole. Our study provides an alternative approach to improve the solubility and modify the release profile of poorly water-soluble drugs such as ketoconazole. |
| first_indexed | 2024-03-10T20:59:02Z |
| format | Article |
| id | doaj.art-c63d37ab872c4141bc815a9061de98a8 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:59:02Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c63d37ab872c4141bc815a9061de98a82023-11-19T17:41:12ZengMDPI AGPharmaceuticals1424-82472023-09-011610134910.3390/ph16101349Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal EngineeringHongmei Yu0Li Zhang1Meiju Liu2Dezhi Yang3Guorong He4Baoxi Zhang5Ningbo Gong6Yang Lu7Guanhua Du8Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaBeijing City Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaBeijing City Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, ChinaTo improve the solubility and dissolution rate of the BCS class II drug ketoconazole, five novel solid forms in 1:1 stoichiometry were obtained upon liquid-assisted grinding, slurry, and slow evaporation methods in the presence of coformers, namely, glutaric, vanillic, 2,6-dihydroxybenzoic, protocatechuic, and 3,5-dinitrobenzoic acids. Single-crystal X-ray diffraction analysis revealed that the hydroxyl/carboxylic acid. . .N-imidazole motif acts as the dominant supramolecular interaction in the obtained solid forms. The solubility of ketoconazole in distilled water significantly increased from 1.2 to 2165.6, 321.6, 139.1, 386.3, and 191.7 μg mL<sup>−1</sup> in the synthesized multi-component forms with glutaric, vanillic, 2,6-dihydroxybenzoic, protocatechuic, and 3,5-dinitrobenzoic acid, respectively. In particular, the cocrystal form with glutaric acid showed an 1800-fold solubility increase in water concerning ketoconazole. Our study provides an alternative approach to improve the solubility and modify the release profile of poorly water-soluble drugs such as ketoconazole.https://www.mdpi.com/1424-8247/16/10/1349cocrystalsaltketoconazolesolubilitydissolution |
| spellingShingle | Hongmei Yu Li Zhang Meiju Liu Dezhi Yang Guorong He Baoxi Zhang Ningbo Gong Yang Lu Guanhua Du Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering Pharmaceuticals cocrystal salt ketoconazole solubility dissolution |
| title | Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering |
| title_full | Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering |
| title_fullStr | Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering |
| title_full_unstemmed | Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering |
| title_short | Enhancing Solubility and Dissolution Rate of Antifungal Drug Ketoconazole through Crystal Engineering |
| title_sort | enhancing solubility and dissolution rate of antifungal drug ketoconazole through crystal engineering |
| topic | cocrystal salt ketoconazole solubility dissolution |
| url | https://www.mdpi.com/1424-8247/16/10/1349 |
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