Novel Esomeprazole Magnesium‐Loaded Dual‐Release Mini‐Tablet Polycap: Formulation, Optimization, Characterization, and In Vivo Evaluation in Beagle Dogs

Abstract

Esomeprazole magnesium (EMP) is a proton pump inhibitor (PPI) that reduces acid se-cretion. EMP has a short plasma half‐life (approximately 1.3 h); hence, nocturnal acid breakthrough (NAB) frequently occurs, disturbing the patient’s nighttime comfort and sleep. We aimed to develop a novel esomeprazole magnesium‐loaded dual‐release mini‐tablet polycap (DR polycap) with a prolonged onset time and improved bioavailability to prevent NAB. The formulation of the EPM mini-tablet core resulted in rapid drug release. The core was coated with an inner coating and an Eu-dragit® L30D‐55 aqueous dispersion coating to prepare the first‐release mini‐tablet. In addition, the core was coated with an inner coating and an aqueous dispersion of Eudragit® S100 and Eudragit® L100 coating to prepare the second‐release mini‐tablet. Each mini‐tablet type was characterized using an in vitro dissolution test and microscopic examination. After testing, 10 of each mini‐tablets were placed together in hard capsules to form DR polycaps. The combination of mini‐tablets was optimized via in vitro release testing and in vivo pharmacokinetic studies. The AUC0–24h of the DR polycap was similar to that of a comparable commercial product (Nexium®); Cmax was lower by approximately 50%, and Tmax was extended by approximately 1.7‐fold. In conclusion, DR polycap is an alternative to commercial products with improved NAB and dosing compliance because of its dual‐release characteristics.