Leonardi Dario, Salomón Claudio J, Lamas María C, Olivieri Alejandro C
IQUIR - CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina.
Int J Pharm. 2009 Feb 9;367(1-2):140-7. doi: 10.1016/j.ijpharm.2008.09.036. Epub 2008 Sep 30.
Benznidazole (BZL) is one of the two therapeutic agents used for the treatment of Chagas' disease. However, the use of BZL in most pharmaceutical preparations and research experiments is still limited due to its low water solubility (0.4mg/mL). To overcome the dissolution rate-limiting step in oral absorption, chitosan microparticles prepared by the coacervation method were chosen, owing to non-toxicity of the polymer and mild conditions of the method. The influence of process parameters such as encapsulation efficiency, size, yield, and dissolution rate was optimized by using artificial neural networks (ANNs). The optimal conditions were found to be 1.5% (w/v) for the polymer concentration, 6.0% (w/v) for the coacervation agent concentration, 1400.0rpm for the stirring rate, and 5.0mL/min for the spraying rate. Confirmation experiments showed good agreement between predicted and experimental values of the optimized properties. These results indicate that ANNs is a valuable tool for the development of optimized BZL chitosan microparticles. To our knowledge it is the first report based on the development of optimized BZL microparticles.
苯硝唑（BZL）是用于治疗恰加斯病的两种治疗药物之一。然而，由于其低水溶性（0.4mg/mL），BZL在大多数药物制剂和研究实验中的应用仍然有限。为了克服口服吸收中的溶出速率限制步骤，选择了通过凝聚法制备的壳聚糖微粒，这是由于该聚合物无毒且该方法条件温和。使用人工神经网络（ANN）优化了诸如包封效率、尺寸、产率和溶出速率等工艺参数的影响。发现最佳条件为聚合物浓度1.5%（w/v）、凝聚剂浓度6.0%（w/v）、搅拌速率1400.0rpm和喷雾速率5.0mL/min。验证实验表明，优化特性的预测值与实验值之间具有良好的一致性。这些结果表明，ANN是开发优化的BZL壳聚糖微粒的有价值工具。据我们所知，这是基于优化的BZL微粒开发的第一份报告。
