Absorption Characteristics of a New Valproate Formulation: Divalproex Sodium‐Coated Particles in Capsules (Depakote® Sprinkle)

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Abstract
To determine the absorption characteristics of a new dosage form of divalproex sodium consisting of coated particles in a pull‐apart capsule (Depakote® Sprinkle, Abbott Laboratories, North Chicago, IL), two absorption studies were conducted in adult volunteers. Ten fasting men participated in a single‐dose, crossover study comparing absorption from Sprinkle capsules versus enteric‐coated tablets (study 1). Eleven men participated in a multidose study (study 2) in which Sprinkle capsules or enteric‐coated tablets were given once every 24 hours for three doses under fasting and nonfasting conditions. In study 1, the extent of absorption from Sprinkle capsules equalled that from enteric‐coated tablets. Compared to enteric‐coated tablets, Sprinkle capsules had earlier absorption onset, 1 versus 2.6 hours (P < .05), slightly slower absorption rate, time to reach peak (tmax) of 4.0 versus 3.4 hours (P > .1), and lower maximum peak plasma drug concentration (Cmax), 20.7 versus 25.9 mcg/mL (P < .05). In study 2, food intake did not affect onset or extent of absorption nor maximum concentration, but did slow rate of absorption. Time to reach peak concentration was 2.7 hours for tablet (fasting), 3.3 hours for capsule (fasting), and 4.8 hours for capsule (nonfasting) (P < .05). Intrasubject absorption performance from the three doses was highly consistent, regardless of food intake. These data indicate that Sprinkle capsules possess desirable absorption characteristics in a form that makes ingestion easier for patients who have difficulty taking other valproate dosage forms.