Evaluation of microcrystalline chitosans for gastro-retentive drug delivery

In vivo absorption studies were carried out in human volunteers to evaluate whether microcrystalline chitosan (MCCh) granules would be gastro-retentive. Furosemide, which is site-specifically absorbed from the upper gastrointestinal tract, was used as model drug. The rate of release of furosemide in vitro could be prolonged by increasing the molecular weight ( M w) or amount of MCCh (150 to 240 kDa; 80 to 95%) in the granules, and also by addition of acidic excipients to the formulations. No marked changes in the in vivo absorption rate ( t max) were noted, but the amounts of furosemide absorbed (AUC 0–∞ and C max) decreased as the in vitro release rate decreased, although this was not statistically significant in the case of AUC. The highest AUC 0–∞ (3050 μg l −1 h) for furosemide (40 mg) was achieved with granules containing 80% MCCh of 150 kDa M w. With MCCh of 240 kDa M w AUC 0–∞ was 1890 μg l −1 h. This kind of pharmacokinetic profile of furosemide suggests that the gastric retention time of the granules is too short in relation to the release rate, and a large amount of the drug passes its “absorption window” before being released. The in vivo study produced no evidence that the chitosan formulations studied can be used as mucoadhesive gastro-retentive drug delivery systems. The results of in vitro mucoadhesion studies did not predict the results of in vivo studies.