In-situ Gel Formulations of Econazole Nitrate: Preparation and In-Vitro and In-Vivo Evaluation

J Pharm Pharmacol. 2011 Oct;63(10):1274-82. doi: 10.1111/j.2042-7158.2011.01315.x. Epub 2011 Aug 30.

Abstract

Objectives: This study describes the in-situ gelling of econazole nitrate containing thermosensitive polymers composed of poloxamer 407 and 188 as a novel treatment platform for vaginal candidiasis.

Methods: Aqueous thermosensitive formulations containing 1% of econazole nitrate and poloxamer 407 and/or 188 were prepared and their rheological, mechanical and drug-release properties determined at 20 ± 0.1°C and/or 37 ± 0.1°C. Based on their biologically suitable thermorheological properties, formulations containing the mixtures of poloxamer 407 and 188 in ratios of 15:15 (F1), 15:20 (F2) and 20:10 (F3) were chosen for comprehensive analysis.

Key findings: Formulations based on F3 exhibited typical gel-type mechanical spectra (G' > G″) at 37°C whereas formulations based on F1 and F2 exhibited properties akin to weakly cross-linked gels. Texture profile analysis demonstrated that F3 showed the highest cohesiveness, adhesiveness, hardness and compressibility. No statistically significant differences (P > 0.5) were observed in the release of econazole nitrate from the formulations at pH 4.5, which in all cases followed anomalous diffusion kinetics. Formulations based on 20% poloxamer 407:10% poloxamer 188 were chosen for in-vivo studies and were shown to be effective for the treatment of the vaginal candidiasis. Histopathologic evaluation also supported the effectiveness of the thermosensitive formulation administered intravaginally.

Conclusion: By careful engineering of the rheological properties, in-situ thermosensitive gel formulations of econazole nitrate were prepared and were shown to be efficacious in the treatment of vaginal candidiasis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida / isolation & purification
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Chemistry, Pharmaceutical
  • Dosage Forms
  • Econazole / administration & dosage*
  • Econazole / pharmacology
  • Econazole / therapeutic use
  • Female
  • Gels
  • Poloxamer
  • Rats, Wistar
  • Rheology
  • Vagina / drug effects
  • Vagina / microbiology
  • Vagina / pathology
  • Vaginitis / drug therapy*
  • Vaginitis / microbiology

Substances

  • Dosage Forms
  • Gels
  • Poloxamer
  • Econazole