SOLUBILITY ENHANCEMENT OF KETOCONAZOLE VIA SALT AND COCRYSTAL FORMATION

Authors

  • Stevanus Hiendrawan Dexa Laboratories of Biomolecular Sciences (DLBS), Industri Selatan V, Block PP no. 7, Jababeka Industrial Estate II, Cikarang, West Java 17550, Indonesia
  • Apriliana Wahyu Hartanti Dexa Laboratories of Biomolecular Sciences (DLBS), Industri Selatan V, Block PP no. 7, Jababeka Industrial Estate II, Cikarang, West Java 17550, Indonesia
  • Bambang Veriansyah Dexa Laboratories of Biomolecular Sciences (DLBS), Industri Selatan V, Block PP no. 7, Jababeka Industrial Estate II, Cikarang, West Java 17550, Indonesia
  • Edward Widjojokusumo Dexa Laboratories of Biomolecular Sciences (DLBS), Industri Selatan V, Block PP no. 7, Jababeka Industrial Estate II, Cikarang, West Java 17550, Indonesia
  • Raymond R. Tjandrawinata Dexa Laboratories of Biomolecular Sciences (DLBS), Industri Selatan V, Block PP no. 7, Jababeka Industrial Estate II, Cikarang, West Java 17550, Indonesia

Keywords:

Cocrystal, Salt, Ketoconazole, Solubility, Stability, Antifungal activities

Abstract

Objective: Pharmaceutical salt and cocrystal is a promising alternative method for improving the solubility and dissolution rate of active pharmaceutical ingredients. In this work, an attempt was made to improve solubility of ketoconazole (KTZ) using salt formation and cocrystallization technique.

Methods: Salt and cocrystal were prepared using oxalic acid (OXA) and fumaric acid (FUMA) via slurry conversion method. Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Scanning Electron Microscope (SEM) techniques were employed to investigate the crystallinity, melting point and morphology of salt and cocrystal respectively. KTZ salt and cocrystal were evaluated further for their solubility, stability and antifungal activities.

Results: Synthesis of KTZ OXA salt and KTZ FUMA cocrystal were successfully carried out using slurry conversion method using ethyl acetate solvent. The result from PXRD, DSC and SEM analysis confirms the formation of salt and cocrystal of KTZ with OXA and FUMA. Saturation solubility studies in water at 25 °C exhibited a remarkable improvement in the drug solubility. KTZ FUMA and KTZ OXA were considered to be stable over the period of 1 month confirmed by the stability study. In vitro antifungal activity study revealed that the formation of KTZ OXA and KTZ FUMA did not alter the therapeutic activity as an antifungal agent.

Conclusion: Salt and cocrystal of KTZ (KTZ OXA and KTZ FUMA) exhibit enhanced solubility compare the pure drug. In vitro antifungal study revealed that both salt and cocrystal of KTZ retained their antifungal activities.

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Published

01-07-2015

How to Cite

Hiendrawan, S., A. W. Hartanti, B. Veriansyah, E. Widjojokusumo, and R. R. Tjandrawinata. “SOLUBILITY ENHANCEMENT OF KETOCONAZOLE VIA SALT AND COCRYSTAL FORMATION”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 7, July 2015, pp. 160-4, https://www.innovareacademics.in/journals/index.php/ijpps/article/view/5570.

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