Overcoming challenges in pediatric formulation with a patient-centric design approach: a proof-of-concept study on the design of an oral solution of a bitter drug

Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP). To conclude on the matching of the developed solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C. However, differences were noted between the stability protocols (unopened recipient and in‐use stability) showing the contribution of the simulation of use to the formation of degradation products. Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation and a photo degradation stability assessment. The developed pediatric solution matched the TPP in all dimensions, namely composition suitable for children, preparation and handling adapted to hospital pharmaceutical compounding and adequate stability and quality. According to the results, in‐use stability protocols should be preferred in the stability evaluation of pediatric formulations.This work was supported by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., Portugal, in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. This research was also supported by and Federal Government of Nigeria NEEDS Assessment grant‐2018. The authors are grateful to FCT (Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020 and UIDP/00690/2020) and to the Associate Laboratory SusTEC (LA/P/0007/2020). Ítala M.G. Marx also acknowledges the Ph.D. research grant (SFRH/BD/137283/2018) provided by FCT.