Accelerating the dissolution of enteric coatings in the upper small intestine: Evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release

Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ system, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5mg/cm2 of partially neutralized EUDRAGIT® L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT® L 30 D-55 was applied at 5mg/cm2. For comparison purposes, a standard single layer of EUDRAGIT® L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1M HCl for 2h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT® L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75min in buffer, whereas release from the EUDRAGIT® L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages in the development of dosage forms designed to release in the upper small intestine.