Pulsatile Delivery Of Modified-Release Esomeprazole Tablets Via Press Coating Technique For Enhanced Chronotherapeutic Efficacy

Abstract

The objective of the present study was to design and evaluate a pulsatile release formulation of Esomeprazole magnesium using a press-coated tablet system intended for chronotherapeutic management of acid-peptic disorders. Esomeprazole, a proton pump inhibitor (PPI), exhibits instability in acidic pH and a short plasma half-life, making it a suitable candidate for time-controlled delivery to match the circadian rhythm of gastric acid secretion, which peaks in the early morning. Core tablets of Esomeprazole were prepared via direct compression and subsequently press-coated with varying ratios of hydroxypropyl methylcellulose (HPMC K4M) and ethyl cellulose (EC) to create a programmable lag time before release. A total of nine formulations (F1–F9) were developed and evaluated for pre-compression flow properties, post-compression physical parameters, and in-vitro drug release. The influence of polymer ratio and coating weight gain on lag time and burst release was statistically analyzed using ANOVA. Among all batches, Formulation F3 (HPMC:EC = 6:1 with 10% coating) was optimized, exhibiting a lag time of 120 minutes and 95.4% drug release within the subsequent hours, achieving a desirable pulsatile profile. The study successfully demonstrates that press-coated pulsatile tablets of Esomeprazole can be effectively utilized for chronotherapy, aligning drug release with the body’s biological rhythms to improve therapeutic outcomes.