Impact of Food and Drink Administration Vehicles on Paediatric Formulation Performance: Part 1-Effects on Solubility of Poorly Soluble Drugs.

Food and drinks are commonly used to facilitate administration of paediatric medicines to improve palatability and enhance patient compliance. However, the impact of this practice on drug solubility and on oral drug bioavailability is not usually studied. Based on recommended strategies for oral administration of paediatric medicines with food and drink vehicles, the aims of this study were (i) to measure the physicochemical properties of (soft) food and drink vehicles, commonly mixed with paediatric medicines prior to administration, and (ii) to assess the impact of the co-administered vehicles on the solubility of two poorly soluble paediatric drugs. Montelukast (sodium) and mesalazine were selected as the model compounds. Distinct differences were observed between the physicochemical properties (i.e. pH, surface tension, osmolality, viscosity and buffer capacity) and macronutrient composition (i.e. fat, sugar and protein content) of the different soft foods and drinks, not only among vehicle type but also within vehicles of the same subtype. Solubility studies of the two model compounds in selected drinks and soft foods resulted in considerably different drug solubility values in each vehicle. The solubility of the drugs was significantly affected by the vehicle physicochemical properties and macronutrient composition, with the solubility of montelukast being driven by the pH, fat and protein content of the vehicles and the solubility of mesalazine by vehicle osmolality, viscosity and sugar content. This vehicle-dependent impact on drug solubility could compromise its bioavailability, and ultimately affect the safety and/or efficacy of the drug and should be taken into consideration during paediatric product development.