中文摘要：肠道感染长期以来一直是一种无声流行病，每年造成全世界数十万人死亡。由于全球抗生素耐药细菌的增加和开发新型小分子抗生素的缓慢，噬菌体治疗等替代疗法已成为控制肠道感染的热门选择。然而，通过口服途径给药对剂型构成了挑战，因为这些活性成分，尤其是相对脆弱的生物实体，容易遭到胃酸的破坏。若将治疗剂封装在能够在低pH条件下生存的pH反应涂层内可以提供这种保护。本研究使用Eudragit（R）S100作为保护性颗粒涂层，海藻糖作为可能活性成分的稳定赋形剂，开发了一种喷雾干燥粉末载体，能够承受与胃环境相当的低pH值。首次采用颗粒形成模型和单分散液滴链技术研究了不同配比和不同水-乙醇溶剂配比下Eudragit-海藻糖复合微粒的形成过程，显示Eudragit壳的形成厚度在0.13μm到0.75μm之间。随后对前景看好的Eudragit-海藻糖制剂进行喷雾干燥，并使用新的阴影成像法研究其在酸性和碱性环境中的存活情况。结果表明，无论溶剂类型如何，Eudragit都能在颗粒中形成保护壳。在pH值为2的条件下，暴露1小时后，Eudragit-海藻糖含量高于5%w/w的海藻糖芯颗粒仍受到保护，表明Eudragit-海藻糖制剂用于肠道给药的潜力。
外文摘要：Enteric infections have long constituted a silent epidemic responsible for hundreds of thousands of deaths around the world every year. Because of the global rise in antibiotic-resistant bacteria and the slow development of new small-molecule antibiotics, alternatives such as bacteriophage therapy have become a much sought-after option in the treatment of enteric infections. However, the administration of therapeutics through the oral route to target gastrointestinal infections poses challenges to dosage formulation because these active ingredients, particularly relatively fragile biological entities, require protection from the stomach's harsh acids. Encapsula-tion of the therapeutics within a pH-responsive coating capable of surviving low pH conditions has the potential to provide such protection. In this study, we developed a spray-dried powder vehicle capable of withstanding low pH comparable to stomach conditions, using Eudragit (R) S100 as a protective particle coating and trehalose as a stabilizing excipient for a possible active component. A particle formation model and a monodisperse droplet chain technique were initially used to study the formation process of Eudragit-trehalose composite microparticles at different ratios and in different ratios of water-ethanol solvent, which showed formation of particles with Eudragit shells varying in thickness from 0.13 mu m to 0.75 mu m. Promising Eudragit-trehalose formulations were subsequently spray-dried and their survival in acidic and alkaline environments studied using a new shadow-graphic imaging method. The results demonstrated that Eudragit was capable of creating a protective shell in the particles irrespective of the type of solvent used to prepare the formulations. The trehalose cores of particles with higher than 5% w/w of Eudragit remained protected after one hour of exposure at pH 2, indicating the potential of Eudragit-trehalose formulations for enteric delivery of drugs.
外文关键词：Eudragit；Enteric drug delivery；Powder；pH-responsive dissolution；Particle engineering；Spray drying；Shadowgraphic imaging
作者：Bin Karim, S；Ordoubadi, M；Wang, H；Gomez, M；Vehring, R
作者单位：Univ Alberta
期刊名称：INTERNATIONAL JOURNAL OF PHARMACEUTICS
期刊影响因子：4.845
出版年份：2021
出版刊次：
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