Abstract
Research shows that topically active infliximab therapy may be efficacious in the treatment of inflammatory bowel disease (IBD) with expected fewer side effects related to systemic exposure. Oral administration of infliximab with site-specific delivery could enable such therapy. In the present study, infliximab was incorporated in a sugar glass matrix (IFX-I) for additional stability and compounding flexibility after which IFX-I was compounded to ileo-colonic-targeted tablets containing 5 mg infliximab (ColoPulse-IFX). Potential critical steps in the production process that may decrease the formulation stability were identified and investigated. Furthermore, the long-term stability of IFX-I (6 months) and ColoPulse-IFX (12 months) stored either at room temperature (25 °C ± 2 °C/60% RH ± 5% RH) or refrigerated (5 °C ± 3 °C) was investigated according to ICH guidelines. Size-exclusion chromatography, fluorescence spectroscopy, and ELISA analyses were used to investigate the infliximab stability, content, tertiary protein structure, and potency at t0, t3, t6, t9, and t12 months. The coating performance of ColoPulse-IFX was investigated in a gastrointestinal simulation system at t0 and t12 months. All the analyses showed that IFX-I and ColoPulse-IFX were stable, potent, and that the coating performance was maintained during the entire storage period at both storage conditions. Thus, IFX-I is a stable dry-powder formulation and ColoPulse-IFX is a promising oral dosage form for the topical treatment of ileo-colonic IBD. This formulation strategy may serve as a new platform for the development of oral peptide or protein formulations that are targeted to the ileo-colonic region in IBD.
Highlights
Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic in flammatory bowel diseases (IBD) that affect the gastrointestinal tract (GIT)
Controlling these steps resulted in a stable IFX-I dry-powder formulation for the production of ColoPulse-IFX, which is an ileo-colonic targeted tablet containing 5 mg infliximab intended for the topical treatment of inflammatory bowel disease (IBD)
The results obtained with size-exclusion chroma tography (SEC), fluorescence spectroscopy, and ELISA showed that the infliximab in IFX-I and ColoPulse-IFX was stable and remained potent up to 6 months and 12 months, respectively, when either stored at room temperature or refrigerated
Summary
Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic in flammatory bowel diseases (IBD) that affect the gastrointestinal tract (GIT). Anti-TNF-α therapy in IBD is efficacious and resolves the disease symptoms that are associated with the elevated TNF-α levels. All the anti-TNF-α therapies in the treatment of IBD are proteins such as monoclonal antibodies or soluble TNF-α receptors and are administered systemically by subcutaneous injections or intravenous infusions [15,16,17]. These routes of administration are reported by IBD patients as undesired and score significantly less favorable compared to oral ther apy [18,19]
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