Dissolution of Once-Nightly Sodium Oxybate in Soft Foods and Alternative Liquid Reconstitution Vehicles.

Abstract

Purpose: Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness (EDS) and can occur with or without cataplexy. Once-nightly sodium oxybate (ON-SXB) is approved for the treatment of cataplexy or EDS in patients 7 years of age or older with narcolepsy. ON-SXB contains both immediate-release and pH-dependent, controlled-release granules designed to be reconstituted in water and administered orally once at bedtime. This study evaluated the dissolution profile of ON-SXB after reconstitution with soft foods and alternative liquid vehicles compared to water.

Methods: ON-SXB 4.5 g and 9 g were reconstituted in soft foods (lemon pudding, low-fat vanilla yogurt, and applesauce) or liquid vehicles (raspberry lemonade solution, fruit punch solution, and alkaline water). Milli-Q water served as the control. Acceptance criteria for product specifications required 40% to 60%, 42% to 62%, and ≥80% dissolution at 15 minutes, 2 hours, and 4 hours, respectively.

Findings: For ON-SXB 4.5 g and 9 g, respectively, mean dissolution at 15 minutes was 48% and 45% for lemon pudding, 50% and 50% for low-fat vanilla yogurt, 49% and 48% for applesauce, 51% and 50% for raspberry lemonade solution, 51% and 51% for fruit punch solution, and 49% and 51% alkaline water; at 2 hours, 50% and 51% for lemon pudding, 51% and 50% for low-fat vanilla yogurt, 50% and 49% for applesauce, 51% and 51% for raspberry lemonade solution, 50% and 51% fruit punch solution, and 50% and 51% alkaline water; and at 4 hours, 96% and 94% for lemon pudding, 91% and 88% for low-fat vanilla yogurt, 95% and 87% for applesauce, 97% and 88% for raspberry lemonade solution, 96% and 89% for fruit punch solution, and 92% and 87% for alkaline water. All tested vehicles met acceptance criteria with ON-SXB 4.5 g and 9 g.

Implications: Lemon pudding, low-fat vanilla yogurt, applesauce, raspberry lemonade solution, fruit punch solution, and alkaline water are viable reconstitution alternatives and maintain the drug dissolution characteristics of ON-SXB when compared to water. Flexibility in the administration of ON-SXB may improve narcolepsy management, enhance medication adherence, and support medication persistency.