Crushing valbenazine capsule contents for potential addition to soft foods or administration via G‑tube

Mello Hebert, Alexander Mar, Richard Moore, Ali Bristow, Brittany Harbert, Scott Siegert

Neurocrine Biosciences, Inc., San Diego, CA

ABSTRACT

Background: Once-daily valbenazine is FDA-approved for tardive dyskinesia and undergoing clinical evaluation for chorea associated with Huntington disease and dyskinetic cerebral palsy. Dysphagia can occur with these disorders, making it difficult to swallow whole medications. Three studies were conducted to evaluate the suitability of mixing crushed contents from valbenazine capsules (40 and 80 mg) with soft foods/liquids or delivering them in water via gastrostomy tube (G-tube).

Methods: In Study 1, whole valbenazine capsules and crushed capsule contents were dissolved in a warm solution. Samples were collected serially over 1 hour for analysis. In Study 2, crushed contents from valbenazine capsules (both doses) were mixed into applesauce, yogurt, and pudding; crushed contents (40 mg) were also added to buffer solutions (pH 1.2, 4.5, 6.8) and fed-state simulated gastric fluid (FeSSGF). In Study 3, crushed valbenazine capsule contents (both doses) were dispersed in tap water (~0° to 50°C) and added to a G-tube, with and without a cup rinse. In Studies 2 and 3, conditions that yielded 90-110% valbenazine recovery were considered acceptable for administration.

Results: In Study 1, rapid and complete drug release (>98% in 15 min) was observed in all samples, independent of preparation (whole capsules, crushed contents) or dose (40 mg, 80 mg). In Study 2, valbenazine recovery was acceptable within 2 hours of adding crushed contents to tested foods, buffers, or FeSSGF (recovery range: 92-102%), with minimal degradants detected. In Study 3, valbenazine recovery was acceptable when crushed capsule contents were dispersed in hot or cold water and a cup rinse was performed (recovery range: 91-97%).

Conclusions: Crushing valbenazine capsule contents did not impact in vitro dissolution performance. Mixing the contents with soft foods/liquids or delivering them in tap water via G‑tube may be acceptable methods for administering valbenazine to patients who have difficulty swallowing.