Albertini Beatrice, Passerini Nadia, Di Sabatino Marcello, Vitali Beatrice, Brigidi Patrizia, Rodriguez Lorenzo
Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
Eur J Pharm Sci. 2009 Mar 2;36(4-5):591-601. doi: 10.1016/j.ejps.2008.12.009. Epub 2008 Dec 25.
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.
本研究旨在评估一种制备黏膜黏附微粒的新方法，并设计一种创新的硝酸益康唑（ECN）阴道给药系统，以增强药物的抗真菌活性。通过喷雾冷凝法制备了七种不同的制剂：使用脂质亲水性基质（Gelucire 53/10）作为载体，并添加了几种黏膜黏附聚合物，如壳聚糖、羧甲基纤维素钠和泊洛沙姆（Lutrol F68和F127）。对所有微粒进行了表征，并比较了它们的形态、粒径、载药量、在模拟阴道液中的溶解度、对黏膜组织的生物黏附性、溶解行为及其物理化学性质。还研究了微粒对白色念珠菌ATCC 10231菌株的抗真菌活性。获得了高产率（>90%，w/w）且主要粒径在100-355μm范围内的非聚集微球。两种泊洛沙姆均显著（p<0.01）提高了低溶解度药物的溶解度和体外生物利用度以及黏膜黏附强度。基于泊洛沙姆/Gelucire的微粒对白色念珠菌生长表现出抑制作用，表明它们可作为阴道念珠菌病的有效治疗方法，具有降低给药频率的潜力。总之，结果表明喷雾冷凝技术可被视为一种用于生产用于ECN阴道给药的黏膜黏附微粒的新型无溶剂方法。
