A novel double-coating approach for improved pH-triggered delivery to the ileo-colonic region of the gastrointestinal tract

作者：Liu Fang; Moreno Paloma; Basit Abdul W^*

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2010, 74(2): 311-315.

DOI：10.1016/j.ejpb.2009.11.008

• Colonic delivery
• Ileal delivery
• Bicarbonate buffers
• Biorelevant dissolution
• Enteric coatings
• pH-responsive polymers
• Enteric polymers
• Polymethacrylates
• Methacrylic acid and methyl methacrylate copolymer
• Inflammatory bowel disease

Oral pH-responsive systems for drug delivery to the ileo-colonic region of the gastrointestinal tract show poor site specificity. Here, we describe a novel double-coating concept, based on the acrylic polymer EUDRAGIT (R) S, which provides improved functionality for targeting performance. The coating system comprises an inner layer of partially neutralised EUDRAGIT (R) S and buffer agent and an outer coat of standard EUDRAGIT (R) S. Tablets containing prednisolone were coated with double-layer formulations with different inner coat compositions. A conventional single coating was also applied for comparison purposes. Dissolution of the coated tablets was assessed using USP II apparatus in 0.1 M HCl for 2 h followed by pH 7.4 physiological bicarbonate buffer (Krebs buffer), a medium which closely resembles the ionic composition and buffer capacity of the fluid in the distal small intestine. Following acid exposure, drug release from the EUDRAGIT (R) S single-layer-coated tablets in pH 7.4 Krebs buffer was delayed for 120 min. Release from the double-coated tablets was significantly faster compared to the single-coated tablets and was found to be affected by the pH and buffer capacity of the inner coat. The drug release lag time from the optimised double-coating formulation with an inner coat consisting of 10% KH(2)PO(4) (neutralisation pH of 8.0) was 40 min. The accelerated coat dissolution and subsequent rapid drug release from the double-coating system can potentially overcome the limitations of conventional EUDRAGIT (R) S coatings for ileo-colonic delivery.

• 出版日期2010-2