Cyclodextrin-based formulations for pediatric patients: pharmaceutical prospectives and toxicological evaluation.

Abstract

Pediatric drug development faces significant challenges due to age-specific physiological differences, with limited approved formulations often resulting in off-label or extemporaneous uses. Oral administration remains the most common route in children, with ideal formulations requiring dosing flexibility and palatability. Cyclodextrins (CDs) have emerged as effective excipients for pediatric applications due to their ability to enhance aqueous solubility, improve chemical stability, and mask unpleasant tastes. Despite their extensive use in adult formulations, their application in pediatric formulations remains limited. Pharmacokinetic studies in juvenile animals reveal age-dependent renal clearance of CDs, with neonates demonstrating delayed elimination. Clinical findings indicate that hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin are generally well tolerated in pediatric populations; however, neonatal use requires caution due to potential accumulation related to immature renal function. Despite limited regulatory approval, CD-based systems have effectively improved pediatric formulations. Advances in pediatric-friendly dosage forms, such as orodisperable tablets, mucoadhesive films, and 3D-printed mini-tablets, have further highlighted the versatility of CDs. Nonetheless, comprehensive safety data and defined regulatory guidelines are essential for broader clinical application. This review outlines the role of CD complexation in pediatric drug delivery, summarizes the relevant pharmacokinetic and toxicity findings in children, and presents examples of CD-based pediatric formulations.