Biorelevant in vitro assessment of dissolution and compatibility properties of a novel paediatric hydrocortisone drug product following exposure of the drug product to child-appropriate administration fluids

Alkindi (R) is a novel oral multi-particulate taste-masked formulation of hydrocortisone for use in children with the rare disease adrenal insufficiency. The objective of the present work was to study the biorelevant dissolution and compatibility properties of Alkindi (R) granules following exposure to administration fluids including breast milk, artificial milk, whole milk and water. To provide in vitro data for a representative patient collective, dosing conditions in neonates, infants and pre-school children were assessed. Experiments included the physicochemical characterisation of the different administration fluids, hydrocortisone solubility experiments and, dissolution experiments in which initial gastric conditions after the administration of a 0.5 or 5 mg dose with 50-200 mL fluid were simulated. The total duration of the dissolution experiments was 240 min to screen both dissolution and compatibility with the different fluids. Dissolution of the 0.5 mg dose was fast and complete in all scenarios, i.e. >= 80% of the dose was released in the neonate and the infant scenario and >= 75% in the pre-school children setup within 30 min. Results for the 5 mg dose were similar to 5-10% lower in all simulated patient scenarios. The results obtained in the present study confirm the compatibility and in-use chemical stability of Alkindi (R) with all studied dosing matrices and that in vivo dissolution and bioavailability of the product will not be affected by the composition of the co-administered fluids studied.