School of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, PR China.
Int J Pharm. 2011 Feb 14;404(1-2):176-9. doi: 10.1016/j.ijpharm.2010.10.042. Epub 2010 Oct 30.
The purpose of the present study was to develop a novel, simple and determination-of-electrical-conductivity-based method to trace the gelling process of injectable biodegradable in situ forming organogels after administration. The electrical conductivity of pH 7.4 PBS solution with different amount of N-methyl-2-pyrrolodone (NMP) and drug-free organogel formulation contained 0.6mL NMP were determined at 37 °C, respectively. The electrical conductivity of PBS solution was linearly proportional to the amount of NMP. Organogel contained 0.6 mL NMP in PBS solution showed a descending of electrical conductivity as time runs, while the value of electrical conductivity was almost a constant at 7.58 ms/cm after 110 min, which was nearly equaled to the electrical conductivity of 0.6 mL NMP in PBS solution (7.59 ms/cm). This data indicated that the diffusion of NMP caused the descending of system electrical conductivity and NMP completely diffused from organogel after 110 min, which led to the constant electrical conductivity. Meanwhile, photographs of organogel showed that the gel formed from periphery to center gradually, and totally formed after 110 min. The diffusion terminal point of NMP from organogel could be perfectly anticipated and controlled by this method. Consequently, this electrochemical method had visually simulated the gelling process and located gelling time of organogel in medium solution by measuring variation of electrical conductivity.
本研究旨在开发一种新颖、简单且基于电导率测定的方法,以追踪可注射生物降解原位形成有机凝胶在给药后的胶凝过程。分别在 37°C 下测定不同量 N-甲基-2-吡咯烷酮 (NMP) 的 pH 7.4 PBS 溶液和不含药物的有机凝胶制剂的电导率,其中有机凝胶制剂含有 0.6mL NMP。PBS 溶液的电导率与 NMP 的量呈线性关系。在 PBS 溶液中含有 0.6mL NMP 的有机凝胶随着时间的推移,电导率呈下降趋势,而在 110 分钟后,电导率值几乎保持在 7.58ms/cm,几乎等于 PBS 溶液中 0.6mL NMP 的电导率(7.59ms/cm)。这一数据表明,NMP 的扩散导致了体系电导率的下降,并且在 110 分钟后,NMP 完全从有机凝胶中扩散出来,导致电导率保持不变。同时,有机凝胶的照片显示,凝胶从外围逐渐向中心形成,在 110 分钟后完全形成。通过这种电化学方法可以完美地预测和控制 NMP 从有机凝胶中的扩散终点。因此,该方法通过测量电导率的变化,以可视化模拟了凝胶化过程,并定位了有机凝胶在介质溶液中的胶凝时间。