In vitro release and in vivo absorption in beagle dogs of meloxicam from Eudragit® FS 30 D-coated pellets

The objective of this study was to develop meloxicam-loaded colon-specific pellets coated with Eudragit® FS 30 D and further evaluate their in vitro release and in vivo absorption in beagle dogs. Meloxicam-loaded cores (drug loading, 4.8%, w/w) were prepared by layering drug-binder (HPMC)–solubilizer (β-cyclodextrin) solution onto nonpareils (710–850 μm) and then coated with a copolymer of methyl acrylate, methyl methacrylate and methacrylic acid (Eudragit® FS 30 D). The obtained pellets with 15% (w/w) coating level had a spherical form and a smooth surface with coating thickness approximately 28 μm. The in vitro drug release from the pellets was pH-dependent with sufficient gastric resistance (pH 1.2: no release; pH 6.8: 6%; pH 7.0: 52%; pH 7.2: 100%; pH 7.4: 100%, after 3 h incubation). In vivo study was carried out using pentagastrin-pretreated beagle dogs. The onset of meloxicam absorption from the coated pellets with 15% (w/w) Eudragit® FS 30 D (3.0 ± 0.8 h) was significantly delayed (p < 0.05) compared to that from the uncoated drug-layered cores (0.6 ± 0.3 h). The area under the meloxicam plasma concentration–time curve (AUC0→96 h) was not significantly different between the two preparations (p > 0.05), although AUC0→96 h obtained after oral administration of coated pellets (142.5 ± 59.6 μg h/ml) was lower than that obtained after administration of uncoated drug-layered cores (180.8 ± 61.9 μg h/ml). These results suggested that meloxicam could be delivered to the colon with 15% (w/w) coating level of Eudragit® FS 30 D and this polymer coating had no significant influence on the relative bioavailability of meloxicam of the pellets.