The effect of food and liquid ph on the integrity of enteric-coated beads from cysteamine bitartrate delayed-release capsules

Abstract

Background: Cysteamine bitartrate delayed-release (DR) capsule (Procysbi ® ) is approved for treatment of nephropathic cystinosis in the USA, Canada, and the EU. The capsules contain cysteamine bitartrate beads that are enteric coated with acid-resistant Eudragit L 30 D-55, preventing drug release in the acidic stomach environment while allowing dissolution of the beads in the more alkaline environment of the small intestine. Patients who have difficulty swallowing capsules can open capsules, sprinkle beads onto 4 ounces of a suitable food or liquid, gently mix, and consume the entire content within 30 minutes. Foods found to be suitable for administration, and described in the Procysbi US labeling, include fruit juices (except grapefruit juice), applesauce, and berry jelly; there are minor variations in the foods and liquids recommended by regulatory authorities in other countries. This study aimed to assess the stability of enteric-coated beads exposed to additional foods at different conditions to expand the list of suitable foods for drug administration. Methods: For each test condition, beads from eight opened 75 mg cysteamine bitartrate DR capsules were gently mixed with test food and maintained at a prespecified temperature and duration; remaining undissolved beads were then recovered from the food. The recovered beads were split into two portions: one assayed for remaining drug content and the other subjected to dissolution testing to assess the effect on the drug-release profile. Results: The results show that bead integrity was maintained when mixed with foods at pH values <5.5 at all time points when refrigerated (2°C–8°C) and at room (20°C–22°C) and lukewarm (37°C–41°C) temperatures. Bead integrity was not maintained when mixed with foods at pH values of ≥5.5 at room temperature. Conclusion: The results from this in vitro dissolution study help in identifying additional foods that may be used for the administration of cysteamine bitartrate DR beads from opened capsules using the sprinkle method.