Better medicines for children; elucidating patient acceptability to guide flexible solid oral dosage form design

A medicine will not elicit its desired therapeutic effect if the patient is not able or willing to take it. The specific needs of the target population must be taken into account in the design of medicines. Evaluation of the effect of formulation factors on patient’s acceptability could guide the development of better medicines for children. Flexible solid oral dosage forms, including multiparticulates and (oro)dispersible formulations, offer advantages over conventional solid and liquid dosage forms to meet the needs of paediatric patients. These advantages include favourable stability profile, suitability for taste masking, flexibility of dose titration and convenient administration. The overall aims of this research were to identify barriers for the development of acceptable medicines for children, to explore methodology for palatability and patient’s acceptability testing and to generate evidence of acceptability of flexible solid oral dosage forms. Methodological tools for the assessment of palatability and acceptability were developed and the use of such tools was explored through a series of investigations in healthy volunteers using model placebo formulations. Pharmaceutical formulation work was performed to optimise formulation design and choice of excipients, integrating manufacturability and patient’s acceptability criteria. A direct comparison between palatability and acceptability outcomes in children and adults was performed, which highlighted the value of conducting studies in adults to provide initial guidance on formulation design. Some of the key formulation factors that affect acceptability of flexible solid oral dosage forms were identified, which can be used to guide the development of more palatable and acceptable medicines. This research also evidenced methodological barriers in the assessment of palatability and patient’s acceptability which are thoroughly discussed in this thesis and will need to be overcome in the future. The knowledge generated by this research is applicable not only to the development of medicines for children, but also for other subsets of the population