In vitro and in vivo evaluation of a pH-, microbiota- and time-based oral delivery platform for colonic release

Several formulation strategies have been proposed for oral colon delivery, particularly for the therapy of in-flammatory bowel disease (IBD). However, targeting the large intestine remains a challenging goal. The aim of this study was to develop and evaluate a novel type of drug delivery system, which is based on multiple drug release triggers for reliable performance. The system consists of: (i) a drug core, (ii) an inner swellable low -viscosity hydroxypropyl methylcellulose (HPMC) layer, and (iii) an outer film coating based on a Eudragit (R) S: high-methoxyl (HM) pectin (7:3 w/w) blend, optionally containing chitosan. Convex immediate release tab-lets (2 or 4 mm in diameter) containing paracetamol or 5-aminosalicylic acid (5-ASA) were coated in a fluid bed. The double-coated tablets exhibited pulsatile release profiles when changing the release medium from 0.1 N HCl to phosphate buffer pH 7.4. Also, drug release was faster in simulated colonic fluid (SCF) in the presence of fecal bacteria from IBD patients compared to control culture medium from tablets with outer Eudragit (R) S: HM pectin: chitosan coatings. The latter systems showed promising results in the control of the progression of colitis and alteration of the microbiota in a preliminary rat study.

Automated summary

A novel drug delivery system based on multiple drug release triggers was developed and evaluated for oral colon delivery, with a specific focus on inflammatory bowel disease (IBD) therapy. The system demonstrated pulsatile drug release in different release media and faster drug release in simulated colonic fluid with fecal bacteria from IBD patients. Promising results were observed in a preliminary rat study, indicating potential therapeutic effects on colitis progression and microbiota alteration.