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

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.