In vitro stability, potency, and dissolution of duloxetine enteric-coated pellets after exposure to applesauce, apple juice, and chocolate pudding

• Published in: Clinical therapeutics 2008-07, Vol.30 (7), p.1300-1308
• Main Authors: Wells, Kevin A., BS, Losin, William G., PharmD
• Format: Article
• Language: English
• Subjects: antidepressant; Antidepressive Agents - chemistry; Beverages; Biological and medical sciences; Cymbalta; Drug Stability; Duloxetine Hydrochloride; Food; food exposure; Food-Drug Interactions; Fruit; Internal Medicine; Medical Education; Medical sciences; Pharmacology. Drug treatments; SNRI; Tablets, Enteric-Coated; Thiophenes - chemistry
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(08)80054-9

Abstract Background: Difficulty swallowing is a common problem in the clinical setting, particularly in elderly patients, and can significantly affect an individual's ability to maintain a proper level of nutrition. Objective: The purpose of this in vitro study was to determine if mixing duloxetine enteric-coated pellets in food substances is an acceptable alternative method for administering this oral formulation to patients with swallowing difficulties. Methods: To determine whether administration in food substances with varying pH values (applesauce and apple juice, pH = ∼3.5; chocolate pudding, pH = ∼5.5–6.0) affects the enteric coating of the formulation, duloxetine pellets (ie, the contents of a 20-mg duloxetine capsule) were exposed to applesauce, apple juice, and chocolate pudding at room temperature and tested in triplicate for potency and impurities; for dissolution, 6 replicates were tested. To assess product stability and integrity of the enteric coating, potency, impurities, and dissolution tests of the pellets were conducted and compared with pellets not exposed to food. The duloxetine pellets were extracted from the food material using a solution of 0.1 normal (N) hydrochloric acid (HCl) prepared from concentrated HCl (commercially available) and deionized water. For the potency and impurities tests, a 40:60 solution of acetonitrile and pH 8.0 phosphate buffer was used as the sample solvent to extract the active pharmaceutical ingredient from the formulation to prepare the samples for testing. The amount of active pharmaceutical ingredient released (in vitro dissolution) from the pellets after exposure to the food substances was determined using 2 media solutions, 0.1 N HCl followed by pH 6.8 phosphate buffer. Applesauce and chocolate pudding were selected as vehicles for oral administration, while apple juice was intended to be used as a wash for a nasogastric tube. Results: Mean (SD) potency results for the 20-mg capsule strength were 20.256 (0.066), 20.222 (0.163), and 19.961 (0.668) mg/capsule for the comparator not exposed to food, the sample exposed to applesauce, and the sample exposed to apple juice, respectively. However, exposure to chocolate pudding altered the integrity of the pellet's enteric coating (mean [SD] potency results, 17.780 [1.605] mg/capsule). Results of impurities testing suggested that none of the test foods caused significant degradation of the drug product. Mean dissolution results found that after 2 hours in 0.1