Aliyar Hyder, Huber Robert, Loubert Gary, Schalau Gerald
Dow Corning Corporation, Healthcare Industry, Pharmaceutics, Midland, Michigan 48686.
Dow Corning Corporation, Healthcare Industry, Pharmaceutics, Midland, Michigan 48686.
J Pharm Sci. 2014 Jul;103(7):2005-2011. doi: 10.1002/jps.23990. Epub 2014 May 5.
The use of silicone as a primary polymer in topical semisolid pharmaceutical formulations is infrequent. Recent development of novel silicone materials provides an opportunity to investigate their drug delivery efficiencies. In this study, an anhydrous semisolid formulation was prepared using a novel cross-linked silicone polymer network swollen in isododecane. Similar formulations were prepared using petrolatum, an acrylic, or a cellulose polymer. All formulations contained 5% ibuprofen (IBP). In vitro permeability was evaluated for all formulations and a commercial product using human cadaver epidermis. The silicone formulation delivered IBP more efficiently than all other formulations in terms of flux, cumulative amount, and percent drug release. The silicone formulation showed the maximum flux of 85.9 μg . cm(-2) . h(-1) and a cumulative IBP release of 261.6 μg in 8 h, whereas the benchmark showed 20.1 μg . cm(-2) . h(-1) and 30.9 μg, respectively. An in vivo study conducted on rats showed calculated blood AUCs of 59.2 and 17.6 μg . h/g (p < 0.003) for the silicone formulation and the benchmark, respectively. The IBP in excised rat skin was 264 ± 59 μg/g for the silicone formulation and 102 ± 5 μg/g for the benchmark. The results obtained from the in vitro and in vivo studies demonstrate efficient topical IBP delivery by the silicone formulation.
在局部半固体制剂中，将硅酮用作主要聚合物的情况并不常见。新型硅酮材料的最新进展为研究其药物递送效率提供了契机。在本研究中，使用一种新型交联硅酮聚合物网络在异十二烷中溶胀制备了无水半固体制剂。使用凡士林、丙烯酸聚合物或纤维素聚合物制备了类似的制剂。所有制剂均含有5%的布洛芬（IBP）。使用人尸体表皮对所有制剂和一种市售产品进行了体外渗透性评估。就通量、累积量和药物释放百分比而言，硅酮制剂比所有其他制剂更有效地递送IBP。硅酮制剂的最大通量为85.9μg·cm⁻²·h⁻¹，8小时内IBP的累积释放量为261.6μg，而基准制剂分别为20.1μg·cm⁻²·h⁻¹和30.9μg。对大鼠进行的体内研究表明，硅酮制剂和基准制剂的计算血药浓度-时间曲线下面积（AUC）分别为59.2和17.6μg·h/g（p<0.003）。硅酮制剂在切除的大鼠皮肤中的IBP含量为264±59μg/g，基准制剂为102±5μg/g。体外和体内研究获得的结果表明，硅酮制剂能有效地进行局部IBP递送。
