Gastro-resistant characteristics of GRAS-grade enteric coatings for pharmaceutical and nutraceutical products

Abstract

The use of naturally derived excipients to develop enteric coatings offers significant advantages over conventional synthetic polymers. Unlike synthetic polymers, they are biodegradable, relatively abundant, have no daily intake limits or restrictions on use for dietary and nutraceutical products. However, little information is available on their dissolution properties under different gastrointestinal conditions and in comparison to each other. This work investigated the gastric resistance properties of commercially available GRAS-based coating technologies. Three coating systems were evaluated: ethyl cellulose+carboxymethyl cellulose (EC-CMC), ethyl cellulose+sodium alginate (EC-Alg) and shellac+sodium alginate (Sh-Alg) combinations. The minimum coating levels were optimized to meet USP pharmacopoeial criteria for delayed release formulations (<10% release after 2h in pH 1.2 followed by >80% release after 45 min of pH change). Theophylline 150 mg tablets were coated with 6.5%, 7%, and 2.75% coating levels of formulations EC-CMC, EC-Alg and Sh-Alg, respectively. In vitro dissolution test revealed a fast release in pH 6.8 for ethyl cellulose based coatings: t80% value of 65 and 45 min for EC-CMC and EC-Alg respectively, while a prolonged drug release from Sh-Alg coating was observed in both pH 6.8 and 7.4 phosphate buffers. However, when more biologically relevant bicarbonate buffer was used, all coatings showed slower drug release. Disintegration test, carried out in both simulated gastric and intestinal fluid, confirmed good mechanical resistance of EC-CMC and EC-Alg coating, and revealed poor durability of the thinner Sh-Alg. Under elevated gastric pH conditions (pH 2, 3 and 4), EC-CMC and EC-Alg coatings were broken after 70, 30, 55 min and after 30, 15, 15 min, respectively, while Sh-Alg coated tablets demonstrated gastric resistance at all pH values. In conclusion, none of the GRAS-grade coatings fully complied with the different biological demands of delayed release coating systems.