title: Thermoresponsive fluconazole gels for topical delivery: rheological and mechanical properties, in vitro drug release and anti-fungal efficacy.
abstract: The aim of this study was to develop thermosensitive gels using poloxamers for topical delivery of fluconazole (FLZ). Eight different formulations containing 1% FLZ in poloxamer and a particular co-solvent (propylene glycol (PG) or Transcutol-P) of various concentrations were prepared. The gels were characterized for transition temperatures, rheological and mechanical properties. FLZ permeability and antifungal effect of the gels were also evaluated. Except for one formulation, all gels exhibited thermosensitive property, i.e. transformed from Newtonian (liquid-like) behavior at 20 °C to non-Newtonian (gel-like) behavior at 37 °C. Transcutol-P increased the transition temperature of the formulations, while the opposite effect was observed for PG. At 37 °C, formulations with high poloxamer concentrations (17%) resulted in high viscosity, compressibility and hardness. Formulations containing 17% poloxamer and 20% Transcutol-P and 10% PG, respectively, exhibited high adhesiveness. No significant differences in the in vitro antifungal activity of FLZ were observed among the formulations suggesting that the gel vehicles did not influence the biological effect of FLZ. FLZ permeability decreased with increasing poloxamer concentration. Formulations containing 17% poloxamer and 20% Transcutol-P and 10% PG seemed to be promising in situ gelling systems for the topical delivery of FLZ.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy and Pharmaceutical Sciences, University of Toledo , Toledo, OH , USA and.
authors.forename: Sarath C R
authors.initials: SC
authors.lastname: Gandra
authors.forename: Sanko
authors.initials: S
authors.lastname: Nguyen
authors.forename: Sami
authors.initials: S
authors.lastname: Nazzal
authors.forename: Alaadin
authors.initials: A
authors.lastname: Alayoubi
authors.forename: Rose
authors.initials: R
authors.lastname: Jung
authors.forename: Jerry
authors.initials: J
authors.lastname: Nesamony
mesh_terms: D000891:Anti-Infective Agents, Local; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004548:Elasticity; D005079:Excipients; D015725:Fluconazole / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D005782:Gels; D055595:Mechanical Phenomena; D008826:Microbial Sensitivity Tests; D012212:Rheology; D012995:Solubility; D013696:Temperature; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D000891:Anti-Infective Agents, Local; D000935:Antifungal Agents; D005079:Excipients; D005782:Gels; D015725:Fluconazole
keywords: Compressibility; fungal infections; permeability; poloxamer; temperature-sensitive; zone of inhibition