Disposition and protective effect against irritation after intravenous and rectal administration of indomethacin loaded nanocapsules to rabbits

Indomethacin loaded poly(D,L-lactide) nanocapsules (PLA-NCs) were investigated after intravenous and rectal administration to rabbits. A rebound of indomethacin plasma concentrations attributed to enterohepatic circulation of indomethacin was observed with all preparations. Following i.v. infusions, results showed that PLA-NCs altered the pharmacokinetics of indomethacin in ways that accelerate the extravascular distribution by enhancing the capture of the colloidal carrier by the liver and, at the same time, modifying the elimination rate of indomethacin. After rectal administration of indomethacin formulations, drug plasma concentration profiles revealed that absorption was more complete and more progressive with nanocapsules than with solution. T-max had nearly the same value for all formulations, and bioavailability of indomethacin by this route was increased by nanoencapsulation. The terminal half-life of indomethacin was significantly lower when the drug was given by the rectal route either in solution by PLA-NCs, as compared to suppository. PLA-NCs exhibited a protective effect against the rectal irritability of indomethacin which can be attributed to the reduction of direct contact of free indomethacin with rectal mucosa.