A novel intravaginal delivery system for itraconazole: in vitro and in vivo evaluation.
The purpose of the present study was to formulate and systematically evaluate in vitro, ex vivo and in vivo performances of itraconazole containing bioadhesive vaginal film. We introduce here a novel intravaginal delivery system for itraconazole based on solid dispersion of itraconazole and hydroxypropyl methylcellulose E15 that improve drug solubility and produce bioadhesive system in presence of other ingredients. Solid dispersions of itraconazole were prepared with hydroxypropyl methylcellulose by a spray drying method and characterized by X-ray diffraction and differential scanning calorimetry. The film was prepared using a solvent evaporation technique. In the in vitro antimicrobial study, it was found that solid dispersion containing formulation improves antimicrobial action of itraconazole. From the ex vivo retention study, it was found that the bioadhesive polymers hold the film upto 7 hours on the vaginal mucosa. In vivo antifungal activity tested against Candida albicans vaginitis in female rats, was found to significantly improve the therapeutic benefit of the drug. At 6 days post-dose, the c.f.u. of Candida albicans was more than 10(3) fold decreased in film treated groups without affecting the morphology of vaginal mucosa. These studies suggested that bioadhesive vaginal film is a novel approach for delivery of itraconazole as topical drug delivery system for treating vaginal candidiasis.
Dobaria
N B
NB
Centre of Relevance and Excellence in Novel Drug Delivery Systems, Pharmacy Department, G.H. Patel Building, The M.S. University of Baroda, Vadodara - 390 002, India. dobarianitin@rediffmail.com
Mashru
R C
RC
Badhan
A C
AC
Thakkar
A R
AR
D000268:Adhesiveness; D000282:Administration, Intravaginal; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002176:Candida albicans / Q000187:drug effects / Q000302:isolation & purification; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005260:Female; D065347:Hypromellose Derivatives; D017964:Itraconazole / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep; D014621:Vagina / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D014961:X-Ray Diffraction
D005079:Excipients; D017964:Itraconazole; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008747:Methylcellulose