Time-controlled oral delivery systems for colon targeting

Abstract

In recent years, many research efforts have been spent in the achievement of selective delivery of drugs into the colon following oral administration. Indeed, colonic release is regarded as a beneficial approach to the pharmacological treatment or prevention of widespread large bowel pathologies, such as inflammatory bowel disease and adenocarcinoma. In addition, it is extensively explored as a potential means of enhancing the oral bioavailability of peptides, proteins and other biotechnological molecules, which are known to be less prone to enzymatic degradation in the large, rather than in the small, intestine. Based on these premises, several formulation strategies have been attempted in pursuit of colonic release, chiefly including microflora-, pH-, pressure- and time-dependent delivery technologies. In particular, this review is focused on the main design features and release performances of time-controlled devices, which rely on the relative constancy that is observed in the small intestinal transit time of dosage forms.

Pectin Matrix as Oral Drug Delivery Vehicle for Colon Cancer Treatment

“…Time-dependent systems exploit gastrointestinal transit time as a tool to tune drug delivery to the colon by means of a suitably delayed release profile (33). It is practically difficult to utilize transit time as a measure to target drug delivery of these systems at colon.…”

Drug Targeting in IBD Treatment – Existing and New Approaches

“…Various chemical modifications and formulation technologies based on the intestinal physiology (motility, intraluminal pH, and intestinal transit times) as well as distribution of IBD in the GI tract have been developed in order to improve the efficacy and precision of drug release to the affected areas. These conventional approaches are mainly focused to targeting a particular site in the GI tract and delivery of prodrugs, colonic microflora activated systems, pH dependent and time dependent systems in a form of single or multiunit dosage forms (Gazzaniga et al, 2006;Ishibashi et al, 1998). Delivery strategies and release mechanisms employed in these dosage forms rely on the enzymatic activity of the GI microflora, pH difference between different parts of the GI tract, GI transit time and increased luminal pressure in the colon due to strong peristaltic waves (Leopold, 2001).…”

Liberação específica de fármacos no cólon por via oral. II - Tipos de sistemas utilizados

“…Estes sistemas eliminam a variabilidade associada ao tempo de esvaziamento gástrico e exploram o tempo de trânsito relativamente constante ao longo do intestino delgado. Devem ser estáveis no ambiente ácido do estômago e, após a passagem ao intestino, acionar o mecanismo responsável pelo tempo pré-determinado de latência (Gazzaniga et al, 1995), o qual deve simular a permanência do sistema no intestino delgado e posteriormente deve liberar o princípio ativo. Caso seja possível obter um tempo de latência reprodutível, esta estratégia pode ser bastante promissora (Leopold, 1999).…”

“…Sistemas tempo-dependentes com estas caracterís-ticas foram desenvolvidos por Gazzaniga (Gazzaniga et al, , 1995. Um desses sistemas apresentava a seguinte configuração: i) uma camada externa gastroresistente; ii) uma camada intermediária formada por um polímero hidrofílico (HPMC de elevada viscosidade), com capacidade de intumescer em contato com a água, responsável pelo tempo de latência e iii) um núcleo onde se encontra o fármaco.…”