October 15, 2024

Formulation and Evaluation of Esomeprazole Delayed-Release Tablets Using Multiple Unit Pellet System

Key Points

The formulation using multiple unit pellet system achieved effective delivery of esomeprazole in optimal conditions.
In-vitro dissolution studies showed that tablets maintained %assay and %acid resistance similar to the innovator product.
The assessment included flow properties and multiple coating layers designed to protect the drug in acidic environments.
Stability studies indicated that the formulated tablets performed well under accelerated conditions over three months.

Abstract

Esomeprazole belongs to the Proton-pump inhibitors class of drugs (azoles) that may be taken orally and is used to treatGastroesophageal reflux disease, Peptic ulcers, Heartburns, Duodenal ulcers, Zollinger-Ellison syndrome. The main goalof this study was to formulate and evaluate Esomeprazole Delayed-Release MUPS Tablets. MUPS was designed as delayed-release particles firstly to resist the gastric-acid secretion and secondly to avoid dose dumping. MUPS were formulated by using one of the pelletization techniques i.e., solution-dispersion layering method using Wurster technology. The formulated Multiple Unit Pellets contain four successive coating layers of pre-coating, drug-loading, seal-coating, and enteric-coating onto the inert core (sugar spheres #45-60). These coatings contain inactive ingredients such as Hypromellose AN3, Talc, PEG 6000, Magnesium stearate, Eudragit L30 D, and Titanium dioxide. Eudragit L30 D was used as an enteric-coating polymer on the seal-coated pellets to protect the drug from acidic pH 1.2-3.5 and release it in alkaline pH 6.8. Esomeprazole has a biological half-life of about 1-1.5 hours. MUPS were evaluated for flowproperties and in-vitro drug release. MUPS along with Tableting excipients (MCC Ph 102, PEG 6000, Colloidal silicondioxide, LHPC-LH 11, Crospovidone, and Magnesium stearate) were evaluated for pre- compression parameters. These delayed-release MUPS containing 40mg Esomeprazole were compressed into tablets using the Direct-Compression method then post-compression parameters and %Assay were evaluated. The dissolution studies (in-vitro) were carried out in an acidic medium (0.1 N HCl) for 2hrs and then followed by an alkaline medium (pH 6.8 phosphate buffer) for 1 hr. These tablets were blister-packed and subjected to accelerated stability studies (40ºC±2ºC/75%±5%RH) for 1,2, and 3months and compared with the %assay, %acid resistance, and in-vitro dissolution studies of the initial and innovator results. Based on the results, a formulation whose %assay, % acid resistance, and in-vitro dissolution profile similar to the innovator has been selected as an idealformulation for developing Esomeprazole delayed-release MUPS tablets. Keywords: Proton-Pump Inhibitors (PPI’s), Esomeprazole, Gastroesophageal reflux disease, Zollinger-Ellison syndrome, Wurster, Eudragit L30 D, LHPC LH-11, PEG 6000.

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