Stability of Esomeprazole Capsule Contents After In Vitro Suspension in Common Soft Foods and Beverages

David A. Johnson, M.D., FACP, FACG, Albert C. Roach, Pharm.D., FACG, Anders S. Carlsson, M.Sc., Anders A.S. Karlsson, Ph.D., Dan E. Behr, Ph.D.

Disclosures

Pharmacotherapy. 2003;23(6) 

In This Article

Abstract and Introduction

Study Objective: To determine the in vitro stability of esomeprazole pellets from an opened capsule after suspension in various common soft foods and beverages.
Design: In vitro study.
Setting: Pharmaceutical company research laboratory.
Measurements and Main Results: Pellets from opened esomeprazole 20-mg capsules were suspended in 100 ml of tap water, milk (1.5% fat), orange juice, apple juice, yogurt, or cultured milk for 30 minutes, then added to 500 ml of hydrochloric acid to simulate gastric acid exposure. After a 2-hour incubation, the mixture was filtered through a sieve, and the collected pellets were dissolved in an alkaline solution. Esomeprazole concentrations were measured using reverse-phase liquid chromatography. The stability of the esomeprazole pellets exceeded 98% in all beverages and soft foods except milk.
Conclusion: Administration of the pellets from an opened esomeprazole capsule shortly after suspending them in tap water, yogurt, cultured milk, orange juice, or apple juice may be a practical alternative for patients who cannot swallow an intact capsule. Bioavailability studies comparing esomeprazole administered as an intact capsule to that of the pellets from an opened capsule suspended in these beverages or soft foods are recommended to confirm these findings.

Esomeprazole, the S-enantiomer of omeprazole, is a potent proton pump inhibitor that suppresses gastric acid secretion. A standard 40-mg dose of esomeprazole provides more effective inhibition of gastric acid production than 40 mg of omeprazole (twice the standard dose)[1] and standard doses of all other proton pump inhibitors currently available.[2] Esomeprazole 40 mg/day, delivered in a single dose and continued for up to 8 weeks, provides more rapid symptom resolution and higher rates of healing of erosive esophagitis than either omeprazole or lansoprazole.[3,4] Esomeprazole is currently supplied in the United States as a 20-mg or 40-mg capsule that is swallowed once/day for treatment of erosive esophagitis and symptomatic gastroesophageal reflux disease, for maintenance of healing of erosive esophagitis, and (with amoxicillin and clarithromycin) for eradication of Helicobacter pylori.

Some patients taking proton pump inhibitors have difficulty swallowing capsules or tablets because of general aversion, hyperactive gag reflex, or dysphagia. Dysphagia is present in 37% of patients with erosive esophagitis.[5] Dysphagia is also common in older patients; an estimated 10-30% of people older than 65 years have pain or difficulty with swallowing.[6] Moreover, in one survey, 3.7% of patients receiving omeprazole were unable to swallow the oral capsule.[7] Thus, modes of administration other than an intact capsule are desirable.

All proton pump inhibitors are unstable when exposed to an acidic milieu, such as the stomach. Therefore, they are formulated with an enteric coating that shields the active drug from the acidic gastric environment.[8,9] To examine the in vitro stability of a proton pump inhibitor, the agent first should be exposed to the medium being tested, then to an acidic solution that simulates gastric acidity before measurement of residual intact drug.

The esomeprazole capsule should be swallowed intact and not chewed. Alternatively, the capsule can be easily opened to disperse the enteric-coated pellets into a soft food. Previous studies in humans have demonstrated that the contents of an opened esomeprazole capsule mixed with 1 tablespoon (15 ml) of applesauce are bioequivalent to the intact capsule.[10] The purpose of this study was to determine the in vitro stability of esomeprazole pellets from an opened capsule after suspension in various common soft foods and beverages.

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