Development of an oral formulation of omeprazole

Abstract

Omeprazole has a low water solubility and is chemically labile in an acid environment. In the formulation of an oral dosage form of omeprazole the possibilities of dissolution rate limited absorption and preabsorption degradation must be kept in mind. A water suspension of omeprazole was tested in a pilot bioavailability study. The suspension was given to six healthy, fasting volunteers on two occasions—together with sodium bicarbonate solution and together with the same volume of water. When the suspension was given with water the bioavailability was reduced by about 50% owing to preabsorption degradation. In another bioavailability study the slowest of three granule formulations with differing in vitro dissolution rates showed a reduced extent of absorption.

A controlled-release pellet formulation (enteric-coated) was formulated and tested in a series of bioavailability studies. A single dose given with food resulted in a delayed absorption and possibly lower bioavailability than under fasting conditions. When the granules were given on an empty stomach before the morning meal the length of time between dosage and meal was of no importance. Concomitant administration of a liquid antacid had no influence on the bioavailability of omeprazole.

Key Words:

• Bioavailability
• controlled release
• dosage form
• enteric coating
• omeprazole
• stability