Excipients in Pediatric Formulations: Biopharmaceutical and Toxicological Considerations

Excipients are commonly used in pharmaceutical formulations for a variety of applications such as solubility and stability enhancement, taste-masking, tablet compaction, etc. Excipients are also used in the preparation of pediatric formulations for purposes similar to that of adult formulations. However, excipients that are used in adult formulations may not be suitable for the development of formulations for pediatric use due to toxicity concerns. Toxicity of excipients in pediatric populations is mainly due to rapid developmental changes, slower metabolism and elimination, and varied organ and body composition. For example, solvents such as ethanol and propylene glycol that are commonly used in pediatric formulations as solubility enhancers, showed life-threatening adverse events. Therefore, it is apparent that the use of excipients in pediatric formulations requires additional risk assessment by practitioners to avoid potential toxicity issues. Regulatory agencies in the United States of America and Europe are working together to create and maintain a database of Safety and Toxicity of Excipients for Pediatrics (STEP). The purpose of this book chapter is to review the role of excipients and their toxicity in pediatric formulations along with strategies to mitigate the potential risks of toxicity associated with their use in pediatric patients.