Pediatric extended-release oral formulations: A U.S. market landscape analysis

Abstract

Extended-release (ER) oral formulations provide therapeutic and practical benefits for pediatric patients by minimizing fluctuations in systemic exposure, reducing dosing frequency, and improving adherence. However, few reviews of ER formulations have focused specifically on the pediatric population. Accordingly, this review has two objectives. The first objective is to characterize the current U.S. market landscape of pediatric ER oral drug products using the U.S. Food and Drug Administration (FDA) Pediatric Labeling Changes database (1998 – 2023). The second objective is to evaluate the extent to which existing products address pediatric needs and to identify opportunities for future development based on the findings of this analysis. In the current U.S. market, 42 out of 266 pediatric-labeled oral prescription drugs are ER products. These products are concentrated in attention-deficit/hyperactivity disorder and seizure indications, and most are labeled for children 6 years of age and older. Conventional tablets and multiparticulate capsules are the predominant dosage forms, whereas suspensions, orally disintegrating tablets, and chewable tablets are less commonly represented. Four principal technology platforms are used: matrix systems, ion-exchange resins, functional coatings, and osmotic pumps, often in combination to balance child-appropriate administration with robust release performance. The analysis highlights several opportunities for future development. Expanding ER development into additional chronic pediatric conditions, addressing the lack of options for children younger than 6 years of age, and strengthening pre-competitive knowledge sharing on formulation platforms and technologies represent the key priorities for broadening the availability of safe, effective, and child-friendly ER medicines.

Introduction

Extended-release (ER) oral formulations can be traced back to the 1950s, with the introduction of the Spansule ER capsule technology by Smith Kline & French Laboratories, designed to provide approximately 12 hours of drug release after oral administration.¹ This multiparticulate functional coating system was first applied to Dexedrine (dextroamphetamine sulfate) and subsequently to Contac 600 (phenylpropanolamine hydrochloride and chlorpheniramine maleate). ER oral formulations are designed to deliver the active pharmaceutical ingredient (API) at a predetermined rate and duration and, in some cases, at specific gastrointestinal (GI) sites, to sustain therapeutic plasma concentrations over an extended period.² This controlled delivery helps minimize peak-to-trough fluctuations and maintain relatively constant plasma drug levels within the therapeutic window that would otherwise require frequent dosing with immediate-release (IR) formulations.^3,4 Consequently, ER formulations can reduce dosing frequency while mitigating peak-related adverse effects, thereby improving patient tolerability and adherence.

The development of ER formulations is generally more complex and resource-intensive than that of IR formulations. Designing an ER oral dosage form that achieves the desired in vivo performance frequently requires clinical pharmacokinetic studies evaluating multiple prototypes with different release rates.⁵ Furthermore, manufacturing often involves specialized unit operations, such as bilayer compression, laser drilling, ion-exchange resin complexation, and functional coating, adding manufacturing complexity and costs. Accordingly, development cycles are typically longer and regulatory requirements are more demanding, raising the hurdle to commercialization.⁶

This commercialization hurdle is even higher in pediatric development. Timelines are prolonged by slower patient enrollment, and commercial incentives are reduced by the smaller market. Although ER formulations can offer substantial advantages in children, including once-daily dosing that reduces caregiver burden and the need for school-time administration, their development entails added complexity. Liquid formulations, which have traditionally been regarded as the “gold standard” in pediatrics due to their acceptability for age-appropriate administration and dose flexibility, substantially limit the technological options available for pediatric ER products.⁷ While traditional solid oral dosage forms such as tablets and capsules afford greater technological flexibility, their uptake is often constrained by factors including dose flexibility and swallowability. Moreover, extemporaneous compounding practices that are commonly used to adapt IR formulations for children, such as tablet splitting or dispersion in liquids, are generally unsuitable for ER formulations because they disrupt the release-controlling mechanisms and risk unintended dose dumping. These development constraints, together with higher commercialization hurdles, may reduce incentives for pharmaceutical companies to pursue pediatric ER products.

The need to develop effective, safe, and acceptable medications for children has been increasingly recognized and addressed through legislation and regulatory initiatives since the late 1990s. These efforts include the Pediatric Rule in 1998,⁸ the Best Pharmaceuticals for Children Act (BPCA) in 2002,⁹ and the Pediatric Research Equity Act (PREA) in 2003 in the U.S.,¹⁰ as well as the Paediatric Regulation in 2007 in the European Union.¹¹ Despite a clear therapeutic need for ER formulations in indications common among children, few reviews of ER formulations have focused specifically on the pediatric population. Accordingly, this review has two objectives. The first objective is to characterize the current U.S. market landscape of pediatric ER oral drug products through systematic analysis of the FDA Pediatric Labeling Changes database with respect to therapeutic area, minimum labeled age, commercialization pathway, dosage form, and technology platform. The second objective is to evaluate the extent to which pediatric needs are adequately addressed by existing products and to identify priority opportunities to broaden the availability of safe, effective, and age-appropriate ER oral therapies for children. Together, these analyses are intended to inform the rational design and implementation of future pediatric ER oral formulations.

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Hwee Jing Ong, Y.-H. Kiang, Bhanu Bejgum, Behnoush Khorsand, Fernando Alvarez-Nunez, Pediatric extended-release oral formulations: A U.S. market landscape analysis, Journal of Pharmaceutical Sciences, 2026, 104319, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2026.104319.

Read also our introduction article on Coatings here:

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