Physicochemical and Antifungal Properties of Clotrimazole in Combination with High-Molecular Weight Chitosan as a Multifunctional Excipient

Mar Drugs. 2020 Nov 26;18(12):591. doi: 10.3390/md18120591.

Abstract

Chitosans represent a group of multifunctional drug excipients. Here, we aimed to estimate the impact of high-molecular weight chitosan on the physicochemical properties of clotrimazole-chitosan solid mixtures (CL-CH), prepared by grinding and kneading methods. We characterised these formulas by infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry, and performed in vitro clotrimazole dissolution tests. Additionally, we examined the antifungal activity of clotrimazole-chitosan mixtures against clinical Candida isolates under neutral and acid conditions. The synergistic effect of clotrimazole and chitosan S combinations was observed in tests carried out at pH 4 on Candida glabrata strains. The inhibition of C. glabrata growth reached at least 90%, regardless of the drug/excipient weight ratio, and even at half of the minimal inhibitory concentrations of clotrimazole. Our results demonstrate that clotrimazole and high-molecular weight chitosan could be an effective combination in a topical antifungal formulation, as chitosan acts synergistically with clotrimazole against non-albicans candida strains.

Keywords: Candida spp.; chitosan; clotrimazole; drug–polymer combination; synergistic antifungal activity.

Publication types

  • Comparative Study

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects
  • Candida albicans / growth & development
  • Candida glabrata / drug effects*
  • Candida glabrata / growth & development
  • Chitosan / chemistry
  • Chitosan / pharmacology*
  • Clotrimazole / chemistry
  • Clotrimazole / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Compounding
  • Drug Liberation
  • Drug Synergism
  • Excipients / chemistry
  • Excipients / pharmacology*
  • Hydrogen-Ion Concentration
  • Microbial Sensitivity Tests
  • Molecular Weight
  • Powders
  • Solubility

Substances

  • Antifungal Agents
  • Excipients
  • Powders
  • Chitosan
  • Clotrimazole