Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain.
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain.
Eur J Pharm Sci. 2018 May 30;117:204-215. doi: 10.1016/j.ejps.2018.02.022. Epub 2018 Mar 21.
Sustained-release vaginal microbicides hold out great hope for the prevention of sexual transmission of HIV from men to women. Tenofovir (TFV) -an antiretroviral drug- sustained-release vaginal compacts combining two release control systems (by drug-loading granules with hydrophobic polymers and incorporating them in a hydrophilic matrix) are proposed in this work as a possible microbicide. The polymers used for the drug granules are Eudragit® RS (ERS), an acrylic derivative, and Zein, a maize protein. The hydrophilic matrix is composed of a mixture of hydroxypropylmethyl cellulose (HPMC) and chitosan (CH). The thermal, microscopic, spectrophotometric and X-ray diffraction analysis showed that the drug was not altered during the granulation process. Studies of TFV release, swelling and ex vivo mucoadhesion were subsequently performed on simulated vaginal fluid. The formulation whereby TFV is granulated using twice its weight in ERS, and then including these granules in a matrix in which the CH predominates over HPMC, allows the sustained release of TFV for 144 h, mucoadhesion to the vaginal mucosa for 150 h and a moderate swelling, making it the most suitable formulation of all those studied. These compacts would therefore offer women protection against the sexual acquisition of HIV.
长效阴道杀微生物剂为预防艾滋病毒通过性行为从男性传播给女性带来了很大希望。 本文提出了将两种释放控制系统（通过载药颗粒与疏水性聚合物结合并将其纳入亲水性基质）结合使用的抗逆转录病毒药物替诺福韦（TFV）长效阴道栓剂，作为一种可能的杀微生物剂。 用于药物颗粒的聚合物是 Eudragit® RS（ERS），一种丙烯酸衍生物，和玉米蛋白 Zein。 亲水性基质由羟丙基甲基纤维素（HPMC）和壳聚糖（CH）的混合物组成。 热、微观、分光光度和 X 射线衍射分析表明，药物在造粒过程中没有发生变化。 随后在模拟阴道液中进行了 TFV 释放、溶胀和体外黏膜黏附研究。 用 ERS 两倍量的 TFV 造粒，然后将这些颗粒纳入 CH 多于 HPMC 的基质中的制剂，可以实现 TFV 的持续释放 144 小时，对阴道黏膜的黏附长达 150 小时，适度溶胀，是所有研究制剂中最适合的。 因此，这些阴道栓剂将为女性提供预防艾滋病毒通过性行为获得的保护。
