Pharmacokinetic evaluation of indomethacin ethyl ester-loaded nanoencapsules

Goals were to evaluate indomethacin ethyl ester-nanoencapsules (IndOEt-NC) pharmacokinetics in rats and the in vivo ester conversion to indomethacin (IndOH). After i.v. and oral administration exclusively IndOH was detected in plasma. The AUC(IndOEt-NC)/AUC(IndOH) ratio after i.v.. dosing was 0.68, accounting for dose and molecular weight differences, probably due to increased IndOH clearance after IndOEt-NC administration (alpha = 0.05). The results confirm that antiedematogenic activity reported for IndOEt-NC is due to IndOH. Encapsulation did not protect the ester which in vivo is rapidly released and converted to IndOH, acting as a pro-drug. (c) 2008 Elsevier B.V. All rights reserved.