Departamento de Química Farmacológica y Toxicológica, Universidad de Chile, Santos Dumont 964, 8380494 Santiago, Chile; Advanced Center of Chronic Diseases (ACCDiS), Universidad de Chile. Santos Dumont 964, Independencia, Santiago 8380494, Chile; Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina.
Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000, Rosario, Argentina.
Int J Pharm. 2022 Apr 5;617:121594. doi: 10.1016/j.ijpharm.2022.121594. Epub 2022 Feb 16.
Design of Experiments (DoE) techniques were used to identify and optimize the parameters involved in the formulation of triclabendazole pH-sensitive Eudragit® nanoparticles (NPs). Using a Placket Burmann design, Eudragit® E, Eudragit® RS, and two stabilizers (PVP and PVA) were evaluated for NPs formulation by nanoprecipitation. Based on the screening results, Eudragit E 100® and PVP were selected as excipients, and their levels were studied and optimized using a central composite design, obtaining an optimum nanoparticulated system with a Size of 240 nm, a PDI of 0.420, and a ZP of 46.3 mV. Finally, a full characterization of the optimum system was carried out by XRD, DSC, equilibrium solubility, and dissolution rate in biorelevant mediums. As observed in XRD and DSC, the nanoencapsulation process produced a remarkable reduction in drug crystallinity that improved drug solubility and dissolution rate. Although more than 90% of TCBZ was dissolved in acidic mediums at 10 min, no increase in solubility or dissolution rate was observed in simulated saliva. Consequently, the development of pH-sensitive Eudragit® NPs would be a promising strategy in developing an immediate gastric release TCBZ formulation for oral delivery.
实验设计（DoE）技术被用于确定和优化三氯苯达唑 pH 敏感型 Eudragit®纳米粒（NPs）制剂中的参数。采用 Placket Burmann 设计，通过纳米沉淀法评估了 Eudragit®E、Eudragit®RS 以及两种稳定剂（PVP 和 PVA）对 NPs 制剂的影响。基于筛选结果，选择 Eudragit E 100®和 PVP 作为赋形剂，并用中心复合设计对其水平进行研究和优化，得到了最佳的纳米粒体系，其粒径为 240nm，PDI 为 0.420，ZP 为 46.3mV。最后，通过 XRD、DSC、平衡溶解度和在生物相关介质中的溶出率对最佳体系进行了全面表征。如 XRD 和 DSC 观察到的，纳米包封过程显著降低了药物结晶度，提高了药物的溶解度和溶出率。虽然在 10 分钟内，超过 90%的 TCBZ 在酸性介质中溶解，但在模拟唾液中未观察到溶解度或溶出率的增加。因此，开发 pH 敏感型 Eudragit®NPs 将是开发用于口服递送的即刻胃释放 TCBZ 制剂的一种有前途的策略。
