title: Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application.
abstract: The purpose of this study was to develop pluronic-based in situ gelling formulations of metronidazole (MTZ) for treatment of bacterial vaginosis, aimed at prolonging the residence time, controlling drug release, enhancing efficacy, decreasing recurrence, and increasing patient compliance. The in situ gel formulations were prepared using different concentrations of pluronic F-127 (PF-127) alone and in combination with pluronic F-68 (PF-68). The prepared formulations were evaluated for their gelation temperature (T(gel)), in vitro drug release, rheological properties, mucoadhesion properties and tolerability by vaginal mucosa in tissue levels. The T(gel) decreased with increasing PF-127 concentration. The T(gel) was modulated by addition of PF-68 to be within the acceptable range of 25-37 °C. With increasing pluronic concentration, the in vitro drug release decreased, viscosity and mucoadhesive force increased. Histopathological examination of rabbit vaginas from the control and treated groups revealed normal histology of the vagina and cervix. Based on the in vitro evaluation of prepared formulations, the in situ gelling liquid formulated with PF-127/PF-68 (20/10 %, m/m) was selected for further clinical evaluation.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Egypt.
authors.forename: El-Sayed Ali
authors.initials: el-SA
authors.lastname: Ibrahim
authors.forename: Sayed
authors.initials: S
authors.lastname: Ismail
authors.forename: Gihan
authors.initials: G
authors.lastname: Fetih
authors.forename: Omar
authors.initials: O
authors.lastname: Shaaban
authors.forename: Khaled
authors.initials: K
authors.lastname: Hassanein
authors.forename: Noura Hassan
authors.initials: NH
authors.lastname: Abdellah
mesh_terms: D000268:Adhesiveness; D000282:Administration, Intravaginal; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005782:Gels; D007700:Kinetics; D008795:Metronidazole / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism; D020442:Poloxamer / Q000737:chemistry*; D011817:Rabbits; D012212:Rheology; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D016585:Vaginosis, Bacterial / Q000188:drug therapy; D014783:Viscosity
chemical_list: D000890:Anti-Infective Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D020442:Poloxamer; D008795:Metronidazole