On the feasibility of spray-dried eudragit-trehalose microparticles for enteric drug delivery

Abstract

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. Encapsulation 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® 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 μm to 0.75 μm. Promising Eudragit-trehalose formulations were subsequently spray-dried and their survival in acidic and alkaline environments studied using a new shadowgraphic 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.