Bioequivalence studies and sugar-based excipients effects on the properties of new generic ketoconazole tablets formulations and stability evaluation by using direct compression method

Abstract

In this work we described the development of a new solid oral formulation of ketoconazole, a broad-spectrum antifungal agent that belongs to the class II of Biopharmaceutics Classification System (BCS). The ketoconazole raw material supplier was selected to present a best flow and compactation. In addition we used direct compression and superdisintegrants associated to polyols to enhance the dissolution of the ketoconazole tablets. The dissolution was evaluated based in level C in vivo/in vitro correlation established. The best formulation was obtained with croscarmellose/maltose association that in the accelerated stability assays presented no differences on quality specifications and no drug-excipients interaction by DSC analyses. In this work it was possible to confirm the use of sugar-based excipients as suitable dissolution enhancers in pharmaceutical technology and real processes conditions.

Keywords::

• Ketoconazole
• dissolution
• direct compression
• polyols
• sugar-based excipients and superdisintegrants

Acknowledgements

We thank the financial support from Brazilian agencies CNPq, CAPES, FAPERJ, and FUJB.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.