Liu, Fang; (2008) A novel approach to accelerate the dissolution of enteric polymer coatings. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Enteric-coated products dissolve rapidly in vitro in simulated intestinal conditions, but in vivo these products can take up to 2 hours to disintegrate in the human small intestine. A variety of approaches were investigated in this study to accelerate the dissolution of conventional enteric coatings in conditions resembling the upper small intestine. pH-sensitive materials (organic acids and swelling polymers) were incorporated into enteric polymer films based on methacrylic acid ethyl acrylate copolymer - Eudragit® L30 D-55 (aqueous) and Eudragit® L100-55 (organic). Both the organic acids and pH-sensitive polymers leached out from the film in pH 1.2 HCl and were not able to accelerate the film dissolution in subsequent buffer. A novel double-coated system was designed based on the film study with organic acids. The system comprises an inner coat of partially neutralized Eudragit® L30 D-55 and organic acid, and an outer coat of normal Eudragit® L30 D-55 coating, applied to a solid core. Prednisolone tablets were coated with the double coating formulations and exhibited good acid resistance. Drug release was substantially accelerated from the double-coated tablets compared to the single layer Eudragit® L30 D-55 coated (control-coated) tablets in subsequent pH 5.6 phosphate buffer. The drug release lag times for the double-coated and the control-coated tablets were 5 and 100 minutes respectively in buffer. The rapid drug release from the double coating was associated with the faster polymer dissolution velocities measured, compared to the control coating. Confocal laser scanning microscopy revealed that the inner coat of the double coating dissolved before the outer coat and assisted the dissolution of the outer coat. The inner coat ionic strength and buffer capacity contribute independently to the acceleration of the outer coat dissolution and corresponding drug release from the double-coated system. This was associated with the migration of ions from the inner to the outer coat during dissolution process, as illustrated by energy dispersive X-ray spectroscopy testing, using sodium as a representative ion. The novel double-coated system offers a means to provide fast drug release in the small intestine and overcome the limitations of conventional enteric coatings.

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