Time-Based Formulation Strategies for Colon Drug Delivery

Abstract

Despite poor absorption properties, delivery to the colon of bioactive compounds administered by the oral route has become a focus of pharmaceutical research over the last few decades. In particular, the high prevalence of Inflammatory Bowel Disease has driven interest because of the need for improved pharmacological treatments, which may provide high local drug concentrations and low systemic exposure. Colonic release has also been explored to deliver orally biologics having gut stability and permeability issues. For colon delivery, various technologies have been proposed, among which time-dependent systems rely on relatively constant small intestine transit time. Drug delivery platforms exploiting this physiological feature provide a lag time programmed to cover the entire small intestine transit and control the onset of release. Functional polymer coatings or capsule plugs are mainly used for this purpose, working through different mechanisms, such as swelling, dissolution/erosion, rupturing and/or increasing permeability, all activated by aqueous fluids. In addition, enteric coating is generally required to protect time-controlled formulations during their stay in the stomach and rule out the influence of variable gastric emptying. In this review, the rationale and main delivery technologies for oral colon delivery based on the time-dependent strategy are presented and discussed.

Colon Delivery of Nutraceutical Ingredients by Food-Grade Polymeric Systems: An Overview of Technological Characterization and Biological Evaluation

“…Such polymers can be used to develop a variety of delivery systems, i.e., from classical matrix tablets to more complex and sophisticated osmotic pressure drug delivery systems. These exploit the peculiar conditions of the intestinal area such as pH variations, presence of enzymes or bacterial metabolic activity, biochemical pathways, time and pressure [1,6,7]. Undoubtedly, more advanced technologies represent a promising approach for colon-specific drug delivery, e.g., microspheres, nanoparticles, liposomes, mini-capsules, and mini-tablets.…”

“…In the development of controlled-release systems, they are often used in combination to obtain systems capable of resisting stomach acidity and hydrolysis by intestinal enzymes, and then ensuring the release of the substance delivered into the colon through different mechanisms (dissolution/erosion, pH-or time-dependent swelling or degradation, hydrolysis mediated by specific enzymes produced by the colonic bacterial flora, etc.) [1,2,6,7]. Table 1 gathers some physicochemical properties of the polymers that will be further investigated for their applications in colon-targeted food products.…”

“…), number and type of simulated environments (mouth, stomach, intestine, colon and any other specific sections) and their specific reference parameters (simulated environment in empty or fed conditions, pH, travel time, volumes and fluid composition, thus presence or absence of specific enzymes, surfactants, salts, etc.) [7,46,104,[116][117][118][119][120]. Added to this is the common research effort to develop in vitro dissolution/release equipment/protocols with increasing significance and predictivity of the in vivo process [121][122][123].…”

Colon Drug Delivery Systems Based on Swellable and Microbially Degradable High-Methoxyl Pectin: Coating Process and In Vitro Performance

“…Oral colon delivery has been extensively investigated to effectively treat intestinal disorders, such as primarily inflammatory bowel disease (IBD), and to replenish the microbiota [ 1 , 2 , 3 , 4 , 5 ]. Furthermore, it is of interest for the administration of biotechnological drugs, namely peptides, proteins, oligonucleotides and nucleic acids, which may face less harsh conditions in the distal gut as compared with the stomach and small intestine due to lower concentrations of digestive enzymes and physiological surfactants [ 6 , 7 , 8 , 9 ].…”

“…The effect of biodegradation would become even more important in case a high amount of polysaccharide has to be applied to prevent possible premature release in the small bowel. This represents a possible advantage over non-biodegradable swellable/erodible polysaccharides used so far according to the time-dependent colon delivery strategy, which may form a persistent swollen polymer layer hindering timely and complete release at the target site [ 2 , 24 , 25 ]. Such issues have been addressed by incorporating cellulolytic enzymes into a previously described reservoir colon delivery system, either within its hydroxypropyl methylcellulose (HPMC) layer or as an underlying film, with the aim to promote erosion of the functional coating in the colonic region [ 26 ].…”