Purpose The objective of the present work was to screen whether a novel pediatric hydrocortisone granule formulation can be co-administered with common food matrices and liquids. Methods Pediatric hydrocortisone granules were studied using a biopredictive in vitro approach. Experiments included an in situ chemical compatibility study of active ingredient and drug product with liquid dosing vehicles and soft foods commonly ingested by infants, pre-school- and school children. Drug solubility and stability experiments in the different vehicle types and, drug release/dissolution experiments mimicking age-related pediatric gastric conditions after administering the hydrocortisone granules together with the dosing vehicles and after different exposure/mixing times were performed. Results In the simulated dosing scenarios applied in dissolution experiments, in vitro dissolution in gastric conditions was rapid and complete. Results of the chemical compatibility/stability studies indicated that mixing with the different dosing vehicles studied should not be an issue regarding drug degradation products. Conclusions A novel in vitro approach ensuring a proper risk assessment of the use of dosing vehicles in the administration of pediatric dosage forms was established and applied to a novel pediatric hydrocortisone drug product. The studied dosing vehicles were shown to not alter performance of the drug product and are thus considered suitable for administration with hydrocortisone granules.

Accurate prediction of oral absorption of drugs relies on biorelevant methodology. Current methods are based on Western healthy adult populations. Malnourished children have many differences in their gastrointestinal anatomy and physiology compared to a healthy Western adult. These differences may affect the oral absorption of medicines and it is important to gather knowledge on these GI differences in order to develop biorelevant predictive methods for this vulnerable population. A literature search was conducted within PubMed and Scopus to identify papers that describe how gastrointestinal physiology and anatomy is altered in malnourished children. Relevant data was extracted and a narrative review generated to describe how GI differences may affect oral drug absorption. Several differences in GI anatomy and physiology were reported in the literature including: reduced saliva secretion; increased gastric pH; slower gastric emptying; increased levels of bacteria in the small intestine; reduced surface area of intestinal villi and increased intestinal permeability. Much of the data was more than 30 years old and referred to a heterogeneous malnourished population. Sufficient data has been identified that will inform basic novel biorelevant methods to predict oral drug absorption in malnourished children. Further work is required to generate additional data to improve these models and also to verify the models with appropriate pharmacokinetic data.

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Purpose Mixing with liquids or soft foods is a common procedure to improve acceptability of oral medicines in children but may affect drug stability and the in vivo performance of the administered drug product. The aim of the present study was to obtain an overview of the variability of critical attributes of commonly used vehicles and to identify which vehicle characteristics need to be considered when developing in vitro methods for evaluating product quality. Methods One product of each vehicle listed in the FDA draft guidance “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration” was analyzed with regard to composition, calorific content and physicochemical properties. Results The studied vehicles show wide variability, both in composition and physicochemical properties. No correlation was observed between vehicle composition and physicochemical properties. Comparison of results of the present study with previously published data also provided variability in physicochemical properties within individual vehicle types. Conclusions To identify acceptable (qualified) vehicles for global drug product labeling, it is important that the vehicles selected for in vitro compatibility screening reflect the variability in composition and essential physicochemical properties of the vehicles recommended on the product label, rather than relying on results obtained with a single vehicle of each type. Future activities will focus on the development of standardized dosing vehicles that can represent key vehicle characteristics in all their variability to ensure reliable risk assessment.

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