Core-shell tablets designed for modified and sequential release of ibuprofen and rabeprazole

초록

In this study, core–shell tablets comprising an ibuprofen (IBU) enteric-coated core for modified release and a rabeprazole (RAB) shell for immediate release were developed using wet granulation method. The primary aim was to produce a sequential release of RAB and IBU with pharmacokinetic profiles comparable to those of the respective single tablets, thereby reducing the potential for IBU-associated gastrointestinal (GI) side effects. The composition of the IBU/RAB core–shell tablets was finalized on a comparative basis by evaluating various trial formulations. IBU/RAB core–shell tablets (400/20 mg) were assessed for physicochemical attributes, storage stability, and in vivo pharmacokinetics in beagle dogs. IBU/RAB core–shell tablets showed immediate RAB release (99.5 % in 1 h at pH 1.2) and delayed IBU release (3.4 % and 88 % in the acid and buffer stages, respectively). IBU/RAB core–shell tablets produced either comparable or improved plasma concentrations in dogs (Cmax; 1163.3 vs. 1160.0 ng/mL for RAB and 27,370 vs. 24,170 ng/mL for IBU) compared to those of the respective single tablets. The IBU/RAB core–shell tablets also demonstrated long-term and accelerated storage stability. In conclusion, the core–shell design could be a promising strategy for the co-administration and sequential release of IBU and RAB to relieve inflammatory conditions and reduce GI complications. © 2024 Elsevier B.V.

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