Polymer-lipid based mucoadhesive microspheres prepared by spray-congealing for the vaginal delivery of econazole nitrate.
This research aimed to evaluate a new approach for the preparation of mucoadhesive microparticles and to design an innovative vaginal delivery systems for econazole nitrate (ECN) able to enhance the drug antifungal activity. Seven different formulations were prepared by spray-congealing: a lipid-hydrophilic matrix (Gelucire 53/10) was used as carrier and several mucoadhesive polymers such as chitosan, sodium carboxymethylcellulose and poloxamers (Lutrol F68 and F127) were added. All microparticles were characterized and compared for morphology, particle size, drug loading and solubility in simulated vaginal fluid, bioadhesion to mucosal tissue, dissolution behaviour and for their physicochemical properties. The antifungal activity of the microparticles against a strain of Candida albicans ATCC 10231 was also investigated. Non-aggregated microspheres with high yields (>90%, w/w) and with prevalent size in the range 100-355mum were obtained. Both poloxamers significantly (p<0.01) improved the solubility and in vitro bioavailability of the low solubility drug and the mucoadhesive strength. Poloxamers/Gelucire-based microparticles exhibited an inhibition effect on the C. albicans growth, suggesting their use as an effective treatment for vaginal candidiasis, with potential for reduced administration frequency. In conclusion the results demonstrated that spray-congealing technology can be considered a novel and solvent-free approach for the production of mucoadhesive microparticles for the vaginal delivery of ECN.
Albertini
Beatrice
B
Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
Passerini
Nadia
N
Di Sabatino
Marcello
M
Vitali
Beatrice
B
Brigidi
Patrizia
P
Rodriguez
Lorenzo
L
D000269:Adhesives; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001682:Biological Availability; D002176:Candida albicans / Q000187:drug effects; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy; D004464:Econazole / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009092:Mucous Membrane; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014621:Vagina
D000269:Adhesives; D000935:Antifungal Agents; D008055:Lipids; D011108:Polymers; D004464:Econazole