Eudragit-coated albumin nanospheres carrying inclusion complexes for oral administration of indomethacin

Oral administration of indomethacin as well as drugs with low aqueous solubility usually results in poor absorption and bioavailability. The aim of this study was to prepare enteric-coated bovine serum albumin nanospheres carrying cyclodextrin complex for indomethacin delivery. Inclusion complex composed of indomethacin and β-cyclodextrin was prepared by spray-drying. Indomethacin alone and its inclusion complex were incorporated into albumin nanospheres using a coacervation method followed by thermal cross-linking. Then nanosphere suspensions were spray-dried. The inclusion complex and the nanospheres were characterized by FT-IR spectroscopy and DSC analysis. Phase-solubility diagrams and stability constants were determined at pH 2.0 and 7.4 and at different temperatures (10, 25 and 37°C). Swelling ability of nanospheres were evaluated as well as the in vitro release behaviour at pH 2.0 and 7.4. The nanospheres were coated with Eudragit L-100 or S-100 using spray-drying to give protection in the stomach. The results showed that indomethacin solubility can be increased by complexation with β-cyclodextrin or protein/drug interaction with albumin nanospheres. The inclusion complex loaded into BSA nanospheres provided a zero order drug release kinetic. The coating process with EudL and EudS allowed to obtain a negligible release at acidic pH without limit drug availability at pH 7.4.