Colon-Targeted Layer-by-Layer Self-assembled Film: Pharmacokinetic Analysis of BCS Class I and Class III Model Drugs.

Abstract

The aim of the study was to investigate the pharmacokinetic parameters of 5-fluorouracil (5FU) and moxifloxacin HCl (MF) after oral administration using layer-by-layer assembled film in enteric-coated capsule. The layer-by-layer (LbL) film was prepared by sequential layering of chitosan and sodium alginate polyelectrolytes containing either 5FU or MF. The films were in vitro evaluated for physical characteristics, drug loading and release behaviour. In vivo pharmacokinetic evaluation was 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-bilayer film was 147 ± 11.66µm and 212.3 ± 7.19µm after 5FU and MF loading, respectively. 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 24h. 5FU showed non-linear pharmacokinetics compared with linear pharmacokinetics shown 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 720min and 840min for 5FU and MF after oral administration. The mean residence time and AUC0-24 at 45mg/kg were 871.4 ± 6.45min and 198.6 ± 5.03 × 103min per ng/mL and 1267 ± 142.4min and 1590 ± 55.60 103min per ng/mL for 5FU and MF, respectively. Taken together, colon-targeted LbL film can be developed for oral administration of drugs for local and systemic applications.