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 secretion. 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 Eudragit® 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.

Clinical Study on the Eradication of Helicobacter pylori by Vonoprazan Combined with Amoxicillin for 10‐Day Dual Therapy

“…This characteristic often hinders PPIs from achieving 24-hour gastric acid inhibition, potentially leading to night acid breakthrough for patients adhering to the standard twice-daily regimen. 40,41 Consequently, adjusting the frequency of PPI medication to double the standard treatment regimen may present a more appropriate strategy. 42 Such an adjustment ensures continuous and comprehensive gastric acid inhibition, enhancing the effectiveness of amoxicillin, 43,44 and reducing the impact of CYP2C19 gene polymorphism on its efficacy.…”

Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects

“…The DR formulation consists of 2 types of enteric-coated mini tablets, which were designed to release immediately in around 5–10 minutes above pH 5.5 and slowly in around 15–90 minutes above pH 6 to 7. 16 The 1st and the 2nd peaks of esomeprazole in the individual PK profiles of the DR formulation appeared in approximately 1.75 hours and 3–6 hours after administration, respectively ( Figure S1 ). The dual-release pattern of esomeprazole after administration of the DR formulation shows that esomeprazole in the DR formulation was released as expected depending on gastric emptying time, acidity of the proximal (pH 6.6) or distal (pH 7.5) small intestine, 29 and migrating motor complex pattern (85 to 120 minutes).…”

“… 16 In addition, in the in vivo evaluation of the DR formulation in beagle dogs pretreated with pentagastrin, the DR formulation exhibited the dual release pattern with the delayed absorption time, resulting in a longer half-life than the conventional formulation. 16 …”

“…In the in vitro dissolution test, the enteric coatings prevented drug release from acid degradation (for 120 min in 0.1 N HCl), and esomeprazole was released immediately and slowly depending on the types of EC mini tablets in pH 6.8 phosphate buffer. 16 In addition, in the in vivo evaluation of the DR formulation in beagle dogs pretreated with pentagastrin, the DR formulation exhibited the dual release pattern with the delayed absorption time, resulting in a longer half-life than the conventional formulation. 16 Based on the in vitro and in vivo test results, this study aimed to evaluate the PKs and pharmacodynamics (PDs) for the newly developed DR formulation of esomeprazole compared to the conventional EC formulation (Nexium) in healthy male subjects.…”

“…16 In addition, in the in vivo evaluation of the DR formulation in beagle dogs pretreated with pentagastrin, the DR formulation exhibited the dual release pattern with the delayed absorption time, resulting in a longer half-life than the conventional formulation. 16 Based on the in vitro and in vivo test results, this study aimed to evaluate the PKs and pharmacodynamics (PDs) for the newly developed DR formulation of esomeprazole compared to the conventional EC formulation (Nexium) in healthy male subjects. In addition, the gastric acid suppression of esomeprazole for the DR formulation during the night-time was explored compared to the EC formulation.…”