Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös str. 6, Szeged H-6720, Hungary.
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös str. 6, Szeged H-6720, Hungary.
Eur J Pharm Sci. 2022 Jul 1;174:106200. doi: 10.1016/j.ejps.2022.106200. Epub 2022 May 1.
Current study aimed to develop a spray-dried powder containing indomethacin (IND)-loaded polymeric micelles which can be administered perorally as a dissolved powder to enhance the drug release and permeability of the active substance. The resulting low dense spray-dried spherical particles have decreased particle size (7.21 µm) in monodisperse distribution. The polymeric micelles had a nano size range (130 nm) also in monodisperse size distribution. These nanoparticulate properties and the high encapsulation efficiency (> 80%) lead to the improvement of gastrointestinal drug release in fasted and fed state conditions. Following second order and Higuchi kinetics, a rapid drug release was experienced exceeding the initial IND suspension. In vitro cell line studies on Caco-2 human colorectal adenocarcinoma cells showed that the formulation does not increase the toxicity of initial IND, therefore can be considered safe for oral application. Ex vivo semiquantitative and quantitative studies were performed on porcine small intestine where increased flux and permeability values of IND were achieved. The physical stability of the solid formulation was sufficient through a 6-month intermediate study caused by the hydrogen-bond formation between IND and the micelle-forming co-polymer.
本研究旨在开发一种载有吲哚美辛（IND）的聚合物胶束喷雾干燥粉末，可作为溶解粉末口服给药，以增强药物的释放和活性物质的渗透性。所得的低密度喷雾干燥球形颗粒具有减小的粒径（7.21μm）和单分散分布。聚合物胶束也具有纳米尺寸范围（130nm）和单分散尺寸分布。这些纳米颗粒特性和高包封效率（>80%）导致在空腹和进食状态下改善了胃肠道药物的释放。遵循二级和 Higuchi 动力学，经历了快速药物释放，超过了初始 IND 悬浮液的初始药物释放。在 Caco-2 人结肠直肠腺癌细胞的体外细胞系研究中，该制剂没有增加初始 IND 的毒性，因此可以被认为是安全的口服应用。在猪小肠上进行了半定量和定量的离体研究，实现了 IND 的通量和渗透性值的增加。通过 6 个月的中间研究，IND 与形成胶束的共聚物之间形成氢键，使固体制剂的物理稳定性足够。
