Development of Innovative Formulations for Paediatric Use

Children around the world are routinely being treated with medicines that have not been designed and developed for this specific patient population, putting them at risk of inaccurate dosing and side effects. In the view of these considerations, the PhD research project was addressed to the use of specific formulation strategies for the development of innovative paediatric dosage forms. The research has been structured in three case studies, concerning different oral formulations: mucoadhesive buccal films, dispersible granules and complex suspensions. The first part of the research investigated the use of polymeric films for systemic absorption of ondansetron hydrochloride through the buccal mucosa. Several mixtures of hydrophilic polymers were evaluated to optimize the hydration ability of such films, the residence time at the site of application and the drug permeation profile. The second approach was focused on the development of fast dispersible granules for oral administration of praziquantel. Granules represent a flexible dosage form for preschool-aged children that can be given as dispersion in beverages or administered with food, improving the palatability of the formulations and the adherence to therapy. The last part of the work was carried out at the University of Birmingham and faced one of the central challenge associated with paediatric treatment: the taste masking of molecules characterized by bitter taste. To achieve this purpose, polyelectrolyte complexes, composed of whey protein and pectin, and able to encapsulate active substances were developed. Caffeine was selected as model drug for its particularly bitter taste. Finally, the results presented in this thesis demonstrated that specific formulation strategies can be used to overcome the predominant issues related to paediatric administration of medicines, in order to guarantee the complete adherence of children to the therapy and thus the success of the treatment.