Planta Piloto de Ingeniería Química (PLAPIQUI CONICET - Universidad Nacional del Sur), Camino la Carrindanga Km 7, 8000 Bahía Blanca, Argentina.
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Unidad de Tecnología Farmacéutica (UNITEFA, CONICET - UNC), Ciudad Universitaria, 5000 Córdoba, Argentina.
Eur J Pharm Sci. 2014 May 13;55:1-11. doi: 10.1016/j.ejps.2014.01.001. Epub 2014 Jan 20.
The low bioavailability of enalapril maleate associated to its instability in solid state motivated the development of a polyelectrolyte-drug complex between enalapril maleate and the cationic polymethacrylate Eudragit E100. The solid complexes were characterized by DSC-TG, FT-IR and X-ray diffraction. Their aqueous dispersions were evaluated for drug delivery in bicompartimental Franz cells and electrokinetic potentials. Stability in solid state was also evaluated using an HPLC-UV stability indicating method. Absorption of enalapril maleate was assessed thorough the rat everted gut sac model. In addition, urinary recovery after oral administration in rats was used as an indicator of systemic exposition. The solid materials are stable amorphous solids in which both moieties of enalapril maleate are ionically bonded to the polymer. Their aqueous dispersions exhibited controlled release over more than 7h in physiologic saline solution, being ionic exchange the fundamental mechanism that modified the extent and rate of drug release. Intestinal permeation of enalapril maleate was 1.7 times higher in the presence of the cationic polymer. This increase can be related with the capacity to adhere the mucosa due to the positive zeta potential of the complexes. As a consequence bioavailability was significantly improved (1.39 times) after oral administration of the complexes. In addition, no signs of chemical decomposition were observed after a 14months period. The results indicated that the products are new chemical entities that improve unfavorable properties of a useful drug.
马来酸依那普利的生物利用度低与其在固态下的不稳定性有关，这促使我们开发了马来酸依那普利与阳离子型聚甲基丙烯酸酯 Eudragit E100 之间的聚电解质-药物复合物。通过 DSC-TG、FT-IR 和 X 射线衍射对固体复合物进行了表征。评估了它们的水基分散体在双室 Franz 细胞中的药物传递和电动电位。还使用 HPLC-UV 稳定性指示方法评估了固态下的稳定性。通过大鼠外翻肠囊模型评估了马来酸依那普利的吸收。此外，大鼠口服后尿液中的回收情况也被用作全身暴露的指标。这些固体材料是稳定的无定形固体，马来酸依那普利的两个部分都与聚合物通过离子键结合。它们在生理盐水中的水基分散体在 7 小时以上的时间内呈现出控制释放，离子交换是改变药物释放程度和速度的基本机制。阳离子聚合物的存在使马来酸依那普利在肠道中的渗透增加了 1.7 倍。这种增加可能与复合物的正 ζ 电位使其具有粘附黏膜的能力有关。因此，口服复合物后生物利用度显著提高（1.39 倍）。此外，在 14 个月后没有观察到化学分解的迹象。结果表明，这些产物是新的化学实体，可改善有用药物的不利性质。
