Colon targeted layer-by-layer self-assembled film: pharmacokinetic analysis of model drugs after oral administration

Abstract

The aim of the study was to investigate the pharmacokinetic parameters of 5-fluorouracil (5FU) and moxifloxacin (MF) after oral administration using layer-by-layer assembled film in enteric coated capsule. The LbL film was prepared by sequential layering of chitosan and sodium alginate polyelectrolytes containing either 5FU or MF. The films were characterized for physical characteristics, drug loading and release behaviour. Pharmacokinetic studies were performed in the rat model for three different drug concentrations after oral administration and compared with intravenous administration. The results showed that the thickness of 10 bilayerd film was 147 ± 11.66 and 212.3 ± 7.19 µm after 5FU and MF loading, respectively. The amount of 5FU and MF loaded was found to be 1.93 ± 0.48 and 4.64 ± 0.33 mg/cm2, respectively. The DSC and PXRD results showed crystalline nature of 5FU and MF after entrapment in LbL film. The LbL film with backing layer provided directional release of 5FU and MF, where 63.81 ± 4.52% and 101.38 ± 5.08%, respectively was released in 24 h. 5FU showed non-linear pharmacokinetics compared with linear pharmacokinetics showed by MF after oral administration. There is a dose dependent increase in Cmax after oral administration of 5FU and MF LbL film. The Tmax was found to be 720 and 840 mins for 5FU and MF after oral administration. The mean residence time and AUC0-t at 45 mg/kg were 871.4 ± 6.45 min and 198.6 ± 5.03 x 103 min. ng/mL and 1267 ± 142.4 min and 1590 ± 55.60 103 min. ng/mL for 5FU and MF, respectively. Biodistribution studies showed significantly (p<0.01) greater disposition of 5FU within colon tissue after administration using oral LbL film. Taken together, colon targeted LbL film can be developed for oral administration of drugs for local and systemic applications.