Pohlmann Adriana Raffin, Soares Leonardo Uhlmann, Cruz Letícia, da Silveira Nádya Pesce, Guterres Sílvia Stanis Uaski
Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio Grande do Sul, Caixa Postal 15003, CEP 91501-970 Porto Alegre RS, Brazil.
Curr Drug Deliv. 2004 Apr;1(2):103-10. doi: 10.2174/1567201043479920.
To determine the association form of indomethacin in nanocapsules prepared with poly(eta-caprolactone) as polymer and a triglyceride as oil, two methods were studied. The indomethacin ethyl ester was prepared as control, which showed a higher affinity for the oil than the indomethacin. Two differently loaded nanocapsule formulations were prepared. For both formulations, a burst effect was detected using ethanol as release medium. Light scattering (PCS) and NMR analyses suggested the ethanol diffuses through the nanocapsule polymeric wall promoting the total release of indomethacin and its ester. The results showed the inability of this approach to determine the association form of indomethacin. On the other hand, the alkaline hydrolysis of indomethacin and its ester, followed by their disappearance (HPLC), were evaluated. The nanocapsule suspensions containing indomethacin or its ester were treated with 50 mM NaOH. The total disappearance of indomethacin associated with nanocapsules was determined after 2 min, whereas the ester associated with colloids was consumed during 24 h. The constant particle sizes (264 and 259 nm) during the hydrolysis reactions showed that neither the nanocapsules were dissolved nor the polymer sorbed water during the contact with NaOH aqueous solution. The ester rate hydrolysis was determined by its diffusion from the nanocapsules to the interface particle/water. Finally, the indomethacin association model considers the burst release of drug after the addition of NaOH by the formation of its carboxylate, followed by its hydrolysis in aqueous solution promoted by the excess of NaOH. The adsorption was the mechanism of indomethacin association with nanocapsules.
为了确定以聚（ε-己内酯）为聚合物、甘油三酯为油相制备的纳米胶囊中吲哚美辛的缔合形式，研究了两种方法。制备吲哚美辛乙酯作为对照，其对油相的亲和力高于吲哚美辛。制备了两种不同载药量的纳米胶囊制剂。对于这两种制剂，以乙醇作为释放介质时检测到了突释效应。光散射（PCS）和核磁共振分析表明，乙醇扩散穿过纳米胶囊的聚合物壁，促进了吲哚美辛及其酯的完全释放。结果表明，这种方法无法确定吲哚美辛的缔合形式。另一方面，评估了吲哚美辛及其酯的碱性水解，随后通过高效液相色谱法（HPLC）检测它们的消失情况。将含有吲哚美辛或其酯的纳米胶囊悬浮液用50 mM氢氧化钠处理。2分钟后测定与纳米胶囊缔合的吲哚美辛完全消失，而与胶体缔合的酯在24小时内被消耗。水解反应过程中恒定的粒径（264和259 nm）表明，在与氢氧化钠水溶液接触期间，纳米胶囊既未溶解，聚合物也未吸附水。酯的水解速率取决于其从纳米胶囊向颗粒/水界面的扩散。最后，吲哚美辛缔合模型认为，加入氢氧化钠后，药物通过形成羧酸盐而突释，随后在过量氢氧化钠的促进下在水溶液中水解。吸附是吲哚美辛与纳米胶囊缔合的机制。
