Compaction of enteric-coated pellets: influence of formulation and process parameters on tablet properties and in vivo evaluation.

The aim of this study was to investigate the influence of formulation and compression parameters on the properties of tablets, containing enteric-coated pellets, and on the integrity of the enteric polymer of the individual pellets after compression. In addition the piroxicam plasma concentrations were determined after single and multiple oral administration of powder, pellet and tablet formulations at a dose of 0.3 mg piroxicam/kg bodyweight to dogs. Tablets consisted of enteric-coated pellets (containing 2.5% (w/w) piroxicam in combination with microcrystalline cellulose and sodium carboxymethylcellulose (using Avicel PH 101 and Avicel CL 611 in a ratio of 1-3), cushioning waxy pellets and 10% Kollidon CL (as an external disintegrator). From the D-optimality experimental design it was concluded that the ratio of coated pellets to cushioning pellets (CoP/CuP) affected all tablet properties evaluated. Variation of the pellet size and the CoP/CuP ratio resulted in different in vitro tablet disintegration times. Enteric coating of the pellets or compression of the coated pellets did not have a significant influence (P >0.05) on AUC(0-->72 h). Cmax values obtained after oral administration of coated pellets and compressed coated pellets were significantly lower than for the other formulations. Differences in in vitro tablet disintegration times were not reflected in the onset of the piroxicam plasma concentrations. A dosing interval of 48 h prevented piroxicam accumulation following multiple dose administration.