Technology to Obtain Sustained Release Characteristics of Drugs after Delivered to the Colon

Abstract

To determine the necessary technology by which sustained drug release is obtained after drug is delivered to the colon, two kinds of microcapsules were prepared and were filled in a pressure-controlled colon delivery capsule (PCDC). As a model drug 5-aminosalicylic acid (5-ASA) was used, because the target site of 5-ASA is the entire large intestine. 5-ASA was microencapsulated using a water-insoluble polymer, ethylcellulose (EC) or with pH-sensitive polymers, Eudragit L-100 or S-100 and encased in PCDC. The particle size of these microcapsules was around 800 microns and the loading efficiencies of 5-ASA were approximately 90%. In vitro dissolution tests were performed with the prepared microcapsules. The release rate of 5-ASA from the microcapsules was significantly prolonged as compared to 5-ASA powder, although there were no significant differences in the release rates between these microcapsules. By incorporating the 5-ASA microcapsules into PCDC, sustained release PCDCs for colon delivery were prepared and in vivo evaluation was performed using beagle dogs. As a fast release colon delivery system, PCDCs were prepared with 5-ASA powder suspended in suppository base. After oral administration of the test preparations to beagle dogs, plasma 5-ASA concentrations were measured and sustained release characteristics of 5-ASA from the test preparations were evaluated from the plasma 5-ASA concentration-time profiles. The first appearance time of 5-ASA into the systemic circulation after oral administration were 3 h for all the colon delivery preparations and it was thought that these test preparations were delivered to the colon. Both EC microcapsules and Eudragit S-100/RS-100 microcapsules in PCDC showed longer the mean residence time MRT, 8.2 +/- 0.6 h and 8.7 +/- 0.9 h, than Eudragit L-100/RS-100 microcapsules in PCDC where the MRT was 6.6 +/- 0.2 h. Since PCDCs containing 5-ASA powder exhibited a MRT of 7.0 +/- 1.0 h, these two types of preparations have suggested sustained release characteristics.

Stimuli-Sensitive Particles for Drug Delivery

“…[82][83][84] "Smart" cationic and anionic polymers have been used as carriers to enhance oral absorption of peptide and protein drugs across the gastrointestinal tract (GIT). [85][86][87] These pH-sensitive carriers shield the encapsulated drug from the metabolizing enzymes and harsh environment of the GIT while providing a mechanism to tune the site and rate of drug release in response to changes in the environment pH ( Figure 10).…”

Influence of Some Formulation Variables on the Optimization of pH-dependent, Colon-targeted, Sustained-release Mesalamine Microspheres

“…Furthermore, in the case of ulcerative colitis, inflammation is observed in all regions of the colon. Therefore, if 5-ASA is released in a pulsatile manner in the ascending colon, 5-ASA would be diluted during its passage in the colon, consequently insufficient concentration of 5-ASA could be delivered to the transverse and descending colon resulting in reduced clinical effectiveness (3).…”

Drug and Cell Delivery Systems in the Treatment of Colitis

“…The release rate of 5-ASA from the microcapsules was significantly prolonged as compared to 5-ASA powder with no significant differences in the release rates between the microcapsules. The first appearance time of 5-ASA into the systemic circulation after oral administration was 3 h for all the colon delivery preparations, while both EC microcapsules and Eudragit ® S-100/RS-100 microcapsules in PCDCs showed longer mean residence time than Eudragit ® L-100/RS-100 microcapsules, suggesting sustained release characteristics (Hu et al, 1999).…”