Solid-state compatibility screening of excipients suitable for development of indapamide sustained release solid-dosage formulation

Abstract

Differential scanning calorimetry and Fourier transform infrared spectroscopy were applied as screening analytical methods to assess the solid-state compatibility of indapamide (4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoyl-benzamide) with several polymers aimed for development of 24 h sustained release solid-dosage formulation. After the initial research phase which was directed towards selection of suitable polymer matrices, based on their solid-state compatibility with the studied pharmaceutical active ingredient, the second phase of evaluation was intended for compatibility selection of other excipients required to complete a sustained release formulation. The preformulation studies have shown that polyvinylpyrrolydone/polyvinyl acetate might be considered incompatible with indapamide, and the implementation of this polymer career should be avoided in the case of the entitled development. The experimental data additionally have revealed that sorbitol is incompatible with indapamide. The obtained results afforded deeper insight in to the solid-state stability of the studied binary systems and pointed out directions for further development of indapamide sustained release solid-dosage formulation.

Keywords::

• Compatibility
• DSC
• FT-IR
• indapamide
• polymer matrices
• preformulation
• sustained release

Acknowledgment

The authors cordially thank Mrs. Sonja Ugarkovic (R&D, ALKALOID AD) for the support and given useful suggestions during the preparation of the manuscript, Ms. Marina Kajdzanoska (R&D, ALKALOD AD) for the help with the DSC curves and IR spectra collection and Mrs. Bosilka Stefanova (R&D, ALKALOID AD) for the preparation of the tested samples.

Declaration of interest

The authors declare no conflicts of interest.