Stability of Dexlansoprazole MR Granules in Soft Foods and Liquids Appropriate for Alternative Methods of Administration

Abstract

Purpose: The proton pump inhibitor dexlansoprazole (DEX) is a pH-dependent modified release (MR) formulation consisting of 2 types of granules within a single capsule. DEX MR is approved for use in adults for treatment of heartburn associated with symptomatic nonerosive gastroesophageal reflux disease (GERD), healing of erosive esophagitis (EE), maintenance of healed EE and relief of heartburn. The option to administer DEX MR granules mixed with liquids or soft foods is desirable for patients unable to take capsules. The objectives were to assess the in vitro stability of DEX MR granules when mixed with liquids or soft foods and assess the bioavailability (BA) of DEX MR granules mixed with applesauce or water. Methods: The stability of DEX MR granules in soft foods and liquids was determined by an in use stability study. DEX MR capsules were opened and granules were sprinkled on foods or mixed with liquids. After exposing the granules to foods or liquids under ambient conditions, the granules were analyzed for assay and dissolution to determine the DEX potency and the granule enteric coating integrity. Two phase 1, randomized, single-dose, crossover studies were conducted in healthy subjects 18-55 years old. In Study 1, subjects received a single oral dose of DEX MR 90 mg as a capsule or as granules sprinkled on applesauce. In Study 2, subjects received a single oral dose of DEX MR 60 mg as a capsule or an aqueous mixture of granules administered via oral syringe or NG tube. Blood samples for determination of DEX in plasma were collected for 24 hours post-dose. Analyses of variance models were performed, and bioequivalence (BE) between an administration option and the capsule was declared if 90% confidence intervals (CIs) of central value ratios between two regimens for maximum plasma concentration (Cmax) and area under the curve (AUC) were contained within the 0.80-1.25 BE limits. Results: Stability of DEX MR granules was established for at least 1 hour in liquids and soft foods ranging in pH from acidic to near neutral. DEX potency in the granules was not affected by exposing to the soft foods or liquids. The granule enteric coating integrity was well maintained. The 90% CIs for the relative BA of DEX MR 90 mg from granules sprinkled on applesauce to that of the capsule, and the 90% CIs for the relative BA of DEX MR 60 mg from an aqueous mixture of granules to that of the capsule for Cmax and AUCs were within the 0.80-1.25 BE range. Conclusion: Stability of DEX MR granules for 1 hour in liquids and soft foods was established. Administration of DEX MR granules mixed with applesauce or water was BE to the intact capsule. DEX MR granules in liquids or soft foods is expected to provide BA similar to the intact capsule. Disclosure - Michael Kukulka - Employee: Takeda Pharmaceuticals America, Inc. Haiyan Grady - Employee: Takeda Pharmaceuticals America, Inc. Richard Czerniak - Employee: Takeda Pharmaceuticals America, Inc. Jing-tau Wu - Employee: Takeda Pharmaceuticals America, Inc. Claudia Perez - Employee: Takeda Pharmaceuticals America, Inc.