Complexity in Estimation of Esomeprazole and its Related Impurities' Stability in Various Stress Conditions in Low-Dose Aspirin and Esomeprazole Magnesium Capsules

Palavai Sripal Reddy

doi:10.3797/scipharm.1212-13

Abstract

A complex, sensitive, and precise high-performance liquid chromatographic method for the profiling of impurities of esomeprazole in low-dose aspirin and esomeprazole capsules has been developed, validated, and used for the determination of impurities in pharmaceutical products. Esomeprazole and its related impurities’ development in the presence of aspirin was traditionally difficult due to aspirin’s sensitivity to basic conditions and esomeprazole’s sensitivity to acidic conditions. When aspirin is under basic, humid, and extreme temperature conditions, it produces salicylic acid and acetic acid moieties. These two byproducts create an acidic environment for the esomeprazole. Due to the volatility and migration phenomenon of the produced acetic acid and salicylic acid from aspirin in the capsule dosage form, esomeprazole’s purity, stability, and quantification are affected. The objective of the present research work was to develop a gradient reversed-phase liquid chromatographic method to separate all the degradation products and process-related impurities from the main peak. The impurities were well-separated on a RP8 column (150 mm × 4.6mm, X-terra, RP8, 3.5μm) by the gradient program using a glycine buffer (0.08 M, pH adjusted to 9.0 with 50% NaOH), acetonitrile, and methanol at a flow rate of 1.0 mL min−1 with detection wavelength at 305 nm and column temperature at 30°C. The developed method was found to be specific, precise, linear, accurate, rugged, and robust. LOQ values for all of the known impurities were below reporting thresholds. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation in the presence of aspirin. The developed RP-HPLC method was validated according to the present ICH guidelines for specificity, linearity, accuracy, precision, limit of detection, limit of quantification, ruggedness, and robustness.

Highlights

Esomeprazole (Figure 1) is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD), and Zollinger-Ellison syndrome
The primary uses of esomeprazole are for gastroesophageal reflux disease, treatment of duodenal ulcers caused by H. pylori, prevention of gastric ulcers in those on chronic NSAID therapy, and treatment of gastrointestinal ulcers associated with Crohn's disease [1–3]
Challenges were observed in the selection of the stationary phase and mobile phase due to the migration of an impurity that was observed in esomeprazole as salicylic acid, produced from aspirin in the capsules of low-dose aspirin and esomeprazole

Summary

Introduction

Esomeprazole (Figure 1) is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD), and Zollinger-Ellison syndrome. Side effects of aspirin treatment are mainly dyspeptic symptoms, gastrointestinal (GI) lesions, and increased gastrointestinal and overall bleeding, which are consequences of the blockage of prostaglandin synthesis through inhibition of various COX enzymes. This leads to a decrease in mucosal protection, which in turn predisposes the patient to mucosal lesions such as peptic ulcers and peptic ulcer bleeding. Esomeprazole is a proton pump inhibitor (PPI) which is indicated, amongst other indications, for the prevention of gastric and duodenal ulcers associated with NSAID therapy (including aspirin therapy). These are the only lowdose aspirin monotherapy drug products apart from breaking a 300 mg tablet in half, which is probably done by a small proportion of patients taking low-dose aspirin for cardiovascular protection [9–11]

Methods

Results

Conclusion