title: Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: formulation, preparation, and in vitro/in vivo evaluation.
abstract: The purpose of this study was to develop a suitable mucoadhesive in situ gel formulation of clotrimazole (CLO) for the treatment of vaginal candidiasis. For this aim, the mixture of poloxamer (PLX) 407 and 188 were used to prepare in situ gels. Hydroxypropyl methylcellulose (HPMC) K100M or E50 was added to in situ gels in 0.5% ratio to improve the mucoadhesive and mechanical properties of formulations and to prolong the residence time in vaginal cavity. After the preparation of mucoadhesive in situ gels; gelation temperature/time, viscosity, mechanical, mucoadhesive, syringeability, spreadibility and rheological properties, in vitro release behavior, and anticandidal activities were determined. Moreover vaginal retention of mucoadhesive in situ gels was investigated with in vivo distribution studies in rats. Based on the obtained results, it was found that gels prepared with 20% PLX 407, 10% PLX 188 and 0.5% HPMC K100M/E50 might be suitable for vaginal administration of CLO. In addition, the results of in vivo distribution studies showed that gel formulations remained on the vaginal mucosa even 24 h after application. In conclusion, the mucoadhesive in situ gels of CLO would be alternative candidate for treatment of vaginal candidiasis since it has suitable gel properties with good vaginal retention.
authors.affiliation: a Department of Pharmaceutical Technology , Ege University , Bornova , Izmir , Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Rençber
authors.affiliation: a Department of Pharmaceutical Technology , Ege University , Bornova , Izmir , Turkey.
authors.forename: Sinem Yaprak
authors.initials: SY
authors.lastname: Karavana
authors.affiliation: a Department of Pharmaceutical Technology , Ege University , Bornova , Izmir , Turkey.
authors.forename: Zeynep Ay
authors.initials: ZA
authors.lastname: Şenyiğit
authors.affiliation: b Department of Pharmaceutical Microbiology, Faculty of Pharmacy , Ege University , Bornova , Izmir , Turkey.
authors.forename: Bayri
authors.initials: B
authors.lastname: Eraç
authors.affiliation: b Department of Pharmaceutical Microbiology, Faculty of Pharmacy , Ege University , Bornova , Izmir , Turkey.
authors.forename: Mine Hoşgör
authors.initials: MH
authors.lastname: Limoncu
authors.affiliation: a Department of Pharmaceutical Technology , Ege University , Bornova , Izmir , Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Baloğlu
mesh_terms: D000268:Adhesiveness; D000282:Administration, Intravaginal; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D003022:Clotrimazole / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005782:Gels / Q000737:chemistry*; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry*; D009092:Mucous Membrane / Q000378:metabolism; D020442:Poloxamer / Q000737:chemistry*; D017208:Rats, Wistar; D012212:Rheology; D014621:Vagina / Q000378:metabolism / Q000382:microbiology; D014623:Vaginal Diseases / Q000188:drug therapy / Q000382:microbiology; D014783:Viscosity
chemical_list: D000891:Anti-Infective Agents, Local; D000935:Antifungal Agents; D005782:Gels; D020442:Poloxamer; D065347:Hypromellose Derivatives; D003022:Clotrimazole
keywords: Clotrimazole; HPMC; mucoadhesive in situ gel; poloxamer; vaginal candidiasis