CONCLUSIONS
For poorly soluble drugs, in vivo dissolution is likely to be the rate-limiting step of in vivo drug absorption and bioavailability. This study aimed to assess the impact of practices of medicine co-administration with food and drinks on the dissolution behaviour of two compounds. Results show that vehicle-induced changes on drug ionisation percentage and solubility (affected by the pH of the different vehicles), formulation environment (e.g. higher viscosity of the soft foods) and alteration of formulation factors (e.g. different coating of the mesalazine granules) affect drug dissolution behaviour. Drug dissolution was significantly affected by the different vehicles as well as the timing between preparation and testing of the vehicle-drug product mixtures. The use of different vehicles may impact the pharmacokinetic profile of the drug, ultimately altering its clinical performance. For example, alterations in drug bioavailability related to reduced dissolution rates are of concern for drugs that display dissolution as a rate limiting step of absorption, and have a narrow therapeutic index (as the absorbed concentration needed to induce a therapeutic effect may not be reached) or when immediate release is required for fast therapeutic action. Increased drug bioavailability may lead to drug toxicity and adverse clinical side effects. Therefore, it is essential to consider the nature of the vehicles commonly used in practice and the possible effects of different administration recommendations on product performance and, ultimately, clinical performance. The age-appropriate in vitro dissolution test used in this study is a useful biopharmaceutical tool for estimating drug dissolution in conditions relevant to infants. Based on the current experimental setup, it is possible to address paediatric administration scenarios (as done in the current study), as well as testing parameters representative of the different paediatric subgroups (e.g. by using different volumes, agitation rate and media change times). The dissolution setup described has the potential to provide information on the impact of medicine co-administration with vehicles on paediatric formulation performance and is a useful tool for identifying risks associated with this practice.