在这项研究中,我们旨在使用泊洛沙姆407(P407)和188(P188)开发包含氟比洛芬固体分散体(FB-SD)的热敏和生物粘附原位胶凝系统,用于眼科给药。FB-SD是使用P407通过熔融法制备的,其特征在于溶解度,稳定性,SEM,DSC,TGA,和XRD分析。使用冷法和P407/P188(15/26.5%)制备泊洛沙姆混合物和FB-SD的各种配方,在32到35℃之间凝胶,选择开发眼科原位胶凝系统。生物粘附聚合物以三种浓度(0.2、0.4和0.6%(w/w))加入卡波普934P(CP)或羧甲基纤维素(CMC)。凝胶化温度和时间,机械性能,流动属性,并测定粘度值。体外释放速率,释放动力学,并分析了氟比洛芬(FB)从眼用制剂中的释放机理。结果表明,FB-SD在水中的溶解度比FB增加了332倍。振荡研究结果表明,增加生物粘附聚合物浓度降低凝胶化温度和时间,和在较低温度和较短时间内含有CP凝胶的制剂。除F3和F4外,所有制剂均在非生理条件下显示牛顿离子流,而所有制剂在生理条件下都表现出非牛顿假塑性流动。在生理条件下,粘度值随生物粘附聚合物协同作用的增加而增加。质地分析(TPA)表明含CP的配方具有较高的硬度,可压缩性,和粘附性,和配方F4的凝胶结构,含0.6%CP,表现出最大的硬度,可压缩性,和粘附性。体外药物释放研究表明,低于0.6%浓度的CP和CMC没有影响。动力学评估有利于一阶和Hixson-Crowell动力学模型。释放机理分析显示,除了制剂F5之外,制剂的η值大于1,表明FB可能通过超情况II型扩散从眼用制剂中释放。当这项研究的所有结果都被评估时,用含有P407/P188(15/26.5%)和0.2%CP或0.2%CMC或0.4%CMC1%(分别为F2、F5和F6)的FB-SD制备的原位胶凝制剂可能是有希望的制剂,以延长角膜前停留时间并改善FB的眼部生物利用度。
In this study, we aimed to develop thermosensitive and bioadhesive in situ gelling systems containing solid dispersions of flurbiprofen (FB-SDs) using poloxamer 407 (P407) and 188 (P188) for ophthalmic delivery. FB-SDs were prepared with the melt method using P407, characterized by solubility, stability, SEM, DSC, TGA, and XRD analyses. Various formulations of poloxamer mixtures and FB-SDs were prepared using the cold method and P407/P188 (15/26.5%), which gels between 32 and 35 °C, was selected to develop an ophthalmic in situ gelling system. Bioadhesive polymers Carbopol 934P (CP) or carboxymethyl cellulose (CMC) were added in three concentrations (0.2, 0.4, and 0.6% (w/w)). Gelation temperature and time, mechanical properties, flow properties, and viscosity values were determined. The in vitro release rate, release kinetics, and the release mechanism of flurbiprofen (FB) from the ophthalmic formulations were analyzed. The results showed that FB-SDs\' solubility in water increased 332-fold compared with FB. The oscillation study results indicated that increasing bioadhesive polymer concentrations decreased gelation temperature and time, and formulations containing CP gel at lower temperatures and in a shorter time. All formulations except F3 and F4 showed Newtonion flow under non-physiological conditions, while all formulations exhibited non-Newtonion pseudoplastic flow under physiological conditions. Viscosity values increased with an increase in bioadhesive polymer concertation at physiological conditions. Texture profile analysis (TPA) showed that CP-containing formulations had higher hardness, compressibility, and adhesiveness, and the gel structure of formulation F4, containing 0.6% CP, exhibited the greatest hardness, compressibility, and adhesiveness. In vitro drug release studies indicated that CP and CMC had no effect below 0.6% concentration. Kinetic evaluation favored first-order and Hixson-Crowell kinetic models. Release mechanism analysis showed that the n values of the formulations were greater than 1 except for formulation F5, suggesting that FB might be released from the ophthalmic formulations by super case II type diffusion. When all the results of this study are evaluated, the in situ gelling formulations prepared with FB-SDs that contained P407/P188 (15/26.5%) and 0.2% CP or 0.2% CMC or 0.4 CMC% (F2, F5, and F6, respectively) could be promising formulations to prolong precorneal residence time and improve ocular bioavailability of FB.