In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evaluation

• Published in: Journal of pharmacy and pharmacology Vol. 63; no. 10; p. 1274
• Main Authors: Baloglu, Esra, Karavana, Sinem Yaprak, Senyigit, Zeynep Ay, Hilmioglu-Polat, Süleyha, Metin, Dilek Yesim, Zekioglu, Osman, Guneri, Tamer, Jones, David S
• Format: Journal Article
• Language: English
• Published: England 01.10.2011
• Subjects: 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
• ISSN: 2042-7158
• DOI: 10.1111/j.2042-7158.2011.01315.x

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. 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. 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. 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.