Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical Properties
<b>Background</b>: Fluconazole (FLZ) is a broad-spectrum anti-fungal drug presenting poor flowability, mechanical properties, and limited aqueous solubility. These issues pose challenges for the handling and manufacturing of dosage forms of FLZ. The current research aimed to develop fluc...
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2025-03-01
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| author | Ritu Rathi Inderbir Singh Tanikan Sangnim Kampanart Huanbutta |
| author_facet | Ritu Rathi Inderbir Singh Tanikan Sangnim Kampanart Huanbutta |
| author_sort | Ritu Rathi |
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| description | <b>Background</b>: Fluconazole (FLZ) is a broad-spectrum anti-fungal drug presenting poor flowability, mechanical properties, and limited aqueous solubility. These issues pose challenges for the handling and manufacturing of dosage forms of FLZ. The current research aimed to develop fluconazole co-crystal (CC) for improving its aqueous solubility, flowability, and mechanical properties. (2) <b>Methods:</b> The fluconazole benzoic acid (FLZ-BA) co-crystal was prepared using the solvent evaporation technique. The prepared co-crystal was characterized for drug content, solubility, anti-fungal activity, dissolution, and stability. DSC (Differential Scanning Calorimetry), PXRD (Powder X-Ray Diffraction), SEM (Scanning Electron Microscopy), and FTIR (Fourier Transmission Infrared) spectroscopy were carried out to confirm the co-crystal formation. The co-crystal was further evaluated for their flow characteristics and mechanical properties via CTC (compressibility, tabletability, and compactibility), Heckel, and Kawakita analysis. (3) <b>Results</b>: The CC showed 69.51% drug content and 13-fold greater aqueous solubility than pure FLZ. The DSC thermogram showed a sharp endothermic peak between the parent components, a distinct PXRD pattern was observed, and the SEM analysis revealed a different morphology, confirming the formation of co-crystal (new crystalline form). The CC showed immediate drug release and was found to more stable, and less hygroscopic than FLZ alone. The CC revealed better flowability, tabletability (tensile strength), compressibility, and compactibility. Moreover, Heckel and Kawakita analysis indicated the co-crystal to deform plastically, favoring improved compression. (4) <b>Conclusions</b>: The immediate drug release capabilities, improved hygroscopic stability, solubility, better antifungal activity, and flowability make FLZ-BA co-crystal a suitable candidate for the preparation of an immediate drug release dosage form. The study also revealed the application of co-crystal for improving the flowability and mechanical properties. |
| format | Article |
| id | doaj-art-e16aba3b42cc4036b9ad415de7ff6c04 |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-e16aba3b42cc4036b9ad415de7ff6c042025-08-20T02:42:28ZengMDPI AGPharmaceutics1999-49232025-03-0117337110.3390/pharmaceutics17030371Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical PropertiesRitu Rathi0Inderbir Singh1Tanikan Sangnim2Kampanart Huanbutta3Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, IndiaChitkara College of Pharmacy, Chitkara University, Rajpura 140401, IndiaFaculty of Pharmaceutical Sciences, Burapha University, Mueang Chonburi 20131, ThailandDepartment of Manufacturing Pharmacy, College of Pharmacy, Rangsit University, Mueang Pathum Thani 12000, Thailand<b>Background</b>: Fluconazole (FLZ) is a broad-spectrum anti-fungal drug presenting poor flowability, mechanical properties, and limited aqueous solubility. These issues pose challenges for the handling and manufacturing of dosage forms of FLZ. The current research aimed to develop fluconazole co-crystal (CC) for improving its aqueous solubility, flowability, and mechanical properties. (2) <b>Methods:</b> The fluconazole benzoic acid (FLZ-BA) co-crystal was prepared using the solvent evaporation technique. The prepared co-crystal was characterized for drug content, solubility, anti-fungal activity, dissolution, and stability. DSC (Differential Scanning Calorimetry), PXRD (Powder X-Ray Diffraction), SEM (Scanning Electron Microscopy), and FTIR (Fourier Transmission Infrared) spectroscopy were carried out to confirm the co-crystal formation. The co-crystal was further evaluated for their flow characteristics and mechanical properties via CTC (compressibility, tabletability, and compactibility), Heckel, and Kawakita analysis. (3) <b>Results</b>: The CC showed 69.51% drug content and 13-fold greater aqueous solubility than pure FLZ. The DSC thermogram showed a sharp endothermic peak between the parent components, a distinct PXRD pattern was observed, and the SEM analysis revealed a different morphology, confirming the formation of co-crystal (new crystalline form). The CC showed immediate drug release and was found to more stable, and less hygroscopic than FLZ alone. The CC revealed better flowability, tabletability (tensile strength), compressibility, and compactibility. Moreover, Heckel and Kawakita analysis indicated the co-crystal to deform plastically, favoring improved compression. (4) <b>Conclusions</b>: The immediate drug release capabilities, improved hygroscopic stability, solubility, better antifungal activity, and flowability make FLZ-BA co-crystal a suitable candidate for the preparation of an immediate drug release dosage form. The study also revealed the application of co-crystal for improving the flowability and mechanical properties.https://www.mdpi.com/1999-4923/17/3/371co-crystalantifungalsolubilitytabletabilitycompactioncompression |
| spellingShingle | Ritu Rathi Inderbir Singh Tanikan Sangnim Kampanart Huanbutta Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical Properties Pharmaceutics co-crystal antifungal solubility tabletability compaction compression |
| title | Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical Properties |
| title_full | Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical Properties |
| title_fullStr | Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical Properties |
| title_full_unstemmed | Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical Properties |
| title_short | Development and Evaluation of Fluconazole Co-Crystal for Improved Solubility and Mechanical Properties |
| title_sort | development and evaluation of fluconazole co crystal for improved solubility and mechanical properties |
| topic | co-crystal antifungal solubility tabletability compaction compression |
| url | https://www.mdpi.com/1999-4923/17/3/371 |
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