Pharmaceutical additive manufacturing of a pH-responsive core-shell tablet of beta-galactosidase to treat lactase intolerance.

Lactose intolerance affects a significant portion of the global population. Among the proposed treatments for the disease, the main strategy is the use of Lactase, beta-galactosidase, and enzyme before consuming dairy products. The beta-galactosidase enzyme loses its activity in the acidic environment of the stomach before reaching the small intestine environment. In this study, a pH sensitive tablet of beta-galactosidase enzyme with local drug delivery was made for the treatment of lactose intolerance through the hydrogel formulation in the core compartment of the 3D-printed shell of the tablet. The tablets were characterized in terms of morphology, chemical interaction, mechanical properties, dissolution test and pharmacopeial physiochemical requirements. The best polymer weight percentages were selected during the 3D printing of the tablet so that less than 11% release of enzyme within 2 h inside the stomach environment (pH = 1.2) and about 100% enzyme release in the intestinal environment (pH = 6.8) within 6 h was achieved. It should be noted that the enzyme release was confirmed by SDS-PAGE. The recovery of the enzyme activity in tablet was 94%, compared to the activity of the free enzyme. SEM analysis showed smooth, uniform, and continuous layers and the results of FTIR analysis showed no covalent interactions between different materials in the manufacturing process. Furthermore, acceptable tolerances were obtained for pharmacopeial tests including weight variation, content uniformity and assay. According to the results, incorporation of hydrogel into melt extrusion-based 3D printing could be used for producing tailored tablets containing beta-galactosidase enzyme amounts with a delayed release formulation and local oral drug delivery to treat lactose intolerance.