Development and in vitro evaluation of an enteric-coated multiparticulate drug delivery system for the administration of piroxicam to dogs

Abstract

The aim of the study was to develop enteric-coated pellets for the administration of piroxicam (a poorly water-soluble drug) to small animals in order to avoid local gastrointestinal irritation, one of the major side effects of nonsteroidal anti-inflammatory drugs after oral ingestion. Pellets were made by an extrusion–spheronization process. The influence of several excipients on the in vitro drug release was evaluated. Piroxicam release from the uncoated pellets was measured in phosphate buffer (pH 6.8) using the paddle dissolution method (USP XXIII). The enteric-coated pellets were tested in 0.1 N HCl and phosphate buffer, pH 6.8. The addition of sodium croscarmellose (Ac-Di-Sol) did not influence the piroxicam release from microcrystalline cellulose pellets. Sodium carboxymethyl starch (Explotab) increased the release from 30 to 65% at 45 min. The incorporation of sodium carboxymethyl cellulose on its own or as a co-processed blend with microcrystalline cellulose (Avicel RC 581 and CL 611) enhanced the release of piroxicam at 45 min from 30% (pure Avicel PH 101) to 95% (combination of Avicel PH 101 and CL 611 in a ratio of 1:3). Additional use of cyclodextrins had only a minor influence on the dissolution rate. An Eudragit L 30 D-55 and FS 30 D (6/4) film was applied to the core pellets (containing 2.5% (w/w) piroxicam and a combination of Avicel PH 101 and CL 611 in a ratio of 1:3) in order to obtain gastroresistant properties. The coated pellets retained their dissolution characteristics after compression into fast disintegrating tablets because waxy cushioning beads were added to minimize film damage.