Karavasili Christina, Amanatiadou Elsa P, Kontogiannidou Eleni, Eleftheriadis Georgios K, Bouropoulos Nikolaos, Pavlidou Eleni, Kontopoulou Ioanna, Vizirianakis Ioannis S, Fatouros Dimitrios G
Laboratory of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki GR, 54124, Greece.
Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki GR, 54124, Greece; Saint Paul General Hospital, GR-55134 Thessaloniki, Greece.
Int J Pharm. 2017 Aug 7;528(1-2):76-87. doi: 10.1016/j.ijpharm.2017.05.061. Epub 2017 May 30.
Microporous zeolites of distinct framework types, textural properties and crystal morphologies namely BEA, ZSM and NaX, have been employed as carriers to assess their effect on modulating the dissolution behavior of a BCS II model drug (indomethacin). Preparation of the loaded carriers via the incipient wetness method induced significant drug amorphization for the BEA and NaX samples, as well as high drug payloads. The stability of the amorphous drug content was retained after stressing test evaluation of the porous carriers. The dissolution profile of loaded indomethacin was evaluated in simulated gastric fluid (pH 1.2) and simulated intestinal fluids FaSSIF (fasted) and FeSSIF (fed state) conditions and was found to be dependent on the aluminosilicate ratio of the zeolites and the degree of crystalline drug content. The feasibility of the zeolitic particles as oral drug delivery systems was appraised with cytocompatibility and cellular toxicity studies in Caco-2 cultures in a time- and dose-dependent manner by means of the MTT assay and flow cytometry analysis, respectively. Intracellular accumulation of the zeolite particles was observed with no apparent cytotoxic effects at the lower concentrations tested, rendering such microporous zeolites pertinent candidates in oral drug delivery applications.
具有不同骨架类型、织构性质和晶体形态的微孔沸石，即BEA、ZSM和NaX，已被用作载体，以评估它们对调节BCS II类模型药物（吲哚美辛）溶解行为的影响。通过初湿含浸法制备负载型载体，导致BEA和NaX样品中的药物显著非晶化，以及高载药量。在对多孔载体进行强化试验评估后，非晶态药物含量的稳定性得以保留。在模拟胃液（pH 1.2）以及模拟肠液FaSSIF（禁食）和FeSSIF（进食状态）条件下，对负载吲哚美辛的溶出曲线进行了评估，发现其取决于沸石的硅铝比和结晶药物含量的程度。通过MTT试验和流式细胞术分析，分别以时间和剂量依赖性方式，在Caco-2细胞培养物中进行细胞相容性和细胞毒性研究，评估了沸石颗粒作为口服药物递送系统的可行性。在较低测试浓度下，观察到沸石颗粒在细胞内的积累，且无明显细胞毒性作用，这使得此类微孔沸石成为口服药物递送应用中的相关候选物。
