Development of long-acting bioadhesive vaginal gels of oxybutynin: Formulation, in vitro and in vivo evaluations

• Published in: International journal of pharmaceutics Vol. 457; no. 1; pp. 25 - 39
• Main Authors: Tuğcu-Demiröz, Fatmanur, Acartürk, Füsun, Erdoğan, Deniz
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.11.2013
• Subjects: Adhesiveness; Animals; Bioadhesive vaginal gel; Chitosan; Chitosan - chemistry; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Female; HPMC; In Vitro Techniques; Mandelic Acids - administration & dosage; Mandelic Acids - chemistry; Mucous Membrane; Overactive bladder; Oxybutynin; Poloxamer 407; Rabbits; Urinary Bladder, Overactive; Urological Agents - administration & dosage; Urological Agents - chemistry; Vagina - metabolism; Vaginal Creams, Foams, and Jellies - administration & dosage; Vaginal Creams, Foams, and Jellies - chemistry; Osmium tetroxide (PubChem CID: 30318); Poloxamer 407; Glutaraldehyde (PubChem CID: 3485); Glacial acetic acid (PubChem CID: 176); Propiverine (PubChem CID: 4942); Acetonitrile (PubChem CID: 6342); Poloxamer (PubChem CID: 24751); Overactive bladder; Oxybutynin; Bioadhesive vaginal gel; Chitosan; Oxybutynin hydrochloride (PubChem CID: 91505); Hexane (PubChem CID: 8058); HPMC
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.09.003

Overactive bladder (OAB) and vaginal dryness are common problems after menopause. Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than 30 years in the treatment of OAB patients. The aim of the work reported in this paper was to develop long acting mucoadhesive gel formulations of OXY and to investigate their effects on blood levels compared to those of oral OXY immediate release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan, hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127). The physicopharmaceutical properties of gels were evaluated. The gel formulation which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest adhesiveness, cohesiveness and mucoadhesion values. The formulation which was prepared from HPMC K100M showed suitable permeation characteristics across the vaginal mucosa. Comparative bioavailability studies were carried out on rabbits with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and commercially available oral Üropan® tablets. It was concluded that the highest AUC and relative bioavailability values were obtained for the bioadhesive vaginal gel formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of OXY can be a promising and innovative alternative therapeutic system for the treatment of OAB. It can be safely used in cases of overactive bladder and as well as vaginal dryness after menopause.