Objective: This research aimed to make ketoconazole spherical crystals to improve the micromeritic properties and the dissolution rate using the solvent change method. Methods: The solvent that is used in the process of spherical crystallization consists of three types: ether (good solvent), distilled water (bad solvent), and n-hexane (bridging liquid), with a 20:70:10 ratio each. The agglomerates were characterized by differential scanning calorimetry (DSC, powder X-ray diffraction (XRPD), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). Results: Based on PXRD, DSC, and FTIR spectrophotometer results, it was determined that there was no internal change of ketoconazole crystalline structure during the recrystallization process into spherical crystals, and SEM results revealed that the morphology of the crystal became spherical. Based on the micromeritic properties evaluation results, it was concluded that the ketoconazole spherical crystals have superior micromeritic properties than the conventional ketoconazole. The dissolution test results showed an enhancement in the dissolution rate of spherical crystals compared with the untreated ketoconazole. Conclusion: Thus, spherical crystals of ketoconazole appear to be a viable approach for enhancing solubility characteristics and micromeritic properties, which would be highly advantageous for processing ketoconazole as a high-dose drug.
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