Modified-Release Solid Formulations for Colonic Delivery

Solid formulations intended for targeted drug release into the lower gastrointestinal (GI) tract are beneficial for the localized treatment of several diseases and conditions, mainly inflammatory bowel diseases, irritable bowel syndrome and colon cancer. Also, because of their inherent potential to delay or avoid systemic drug absorption from the small intestine, colonic formulations can be utilized for chronotherapy of diseases which are affected by circadian biorhythms (e.g., asthma, hypertension and arthritis), and to achieve clinically relevant bioavailability of drugs that are poorly absorbed from the upper parts of the GI tract because of their polar nature and/or susceptibility to chemical and enzymatic degradation in the small intestine (e.g., proteins and peptides). The purpose of this review is to summarize the recent patent literature concerning various modified-release (MR) formulation technologies that are claimed to provide colonic delivery for a wide array of therapeutic molecules. These technologies either utilize a single or a combination of two or more physiological characteristics of the colon, which includes pH, microflora (enterobacteria), transit time, and luminal pressure. Accordingly, these technologies may be grouped under four distinct classes: pH-controlled (or delayed-release) system, time-controlled (or time-dependent) system, microbially-controlled system, and pressure-controlled system. Among these, formulations that release drugs in response to colonic pH, enterobacteria, or both are most common and promising.