Improvement of the Crystal Stability and Dissolution Profile of Metronidazole by Composite Formation with Microcrystalline Cellulose and Cashew Gum

Abstract

This study was undertaken to improve the solubility of metronidazole by modifying its crystal characteristics using pharmaceutical excipients. Metronidazole granules were formulated with cashew gum (2 – 8% w/w) and microcrystalline cellulose (10% w/w) via kneading, solid dispersion, or physical mixing. Resulting products were characterized: micromeritics, moisture sorption, thermal analysis, Fourier transform infrared spectroscopy (FTIR) and dissolution test. The products exhibited passable/poor flow characteristics; and moisture sorbed was least for granules from kneading process. Melting point and heat of fusion for metronidazole were 163.0oC and 757.8 J/g respectively. Composites’ thermograms revealed that melting point and heat of fusion of metronidazole increased with increase in cashew gum concentration, which indicated higher crystal stability. FTIR spectrum of metronidazole showed peaks of various intensities between 740 and 3415 cm-1.The spectra of the composites were similar to that of the drug, in that every peak present in the drug’s spectrum was observed in the composites’ spectra with minor shifts. Amount of drug released over 60 min was > 80% for composites and < 65% for pure drug. Among the composites, drug release was highest from those containing 8% w/w cashew gum especially from solid dispersion products. The values of the similarity factor showed that while composites from physical mixing displayed similar dissolution profiles with the pure drug, those from kneading and solid dispersion showed dissimilar profiles. The results of this study suggest that cashew gum unlike other polymers improved the solubility of metronidazole by causing the formation of anhydrous instead of amorphous state.

Keywords: Cashew gum, improved metronidazole solubility, anhydrous state, particle engineering