Practical and operational considerations related to paediatric oral drug formulation: An industry survey

Veken, Matthias Van der; Brouwers, Joachim; Budts, Valérie; Lauwerys, Louis; Pathak, Shriram M.; Batchelor, Hannah; Augustijns, Patrick

doi:10.1016/j.ijpharm.2022.121670

Cited by 15 publications

(6 citation statements)

References 38 publications

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“…This lack of characterization is apparent for both in vitro and in silico setups used in pediatric drug development, where scaling is often performed allometrically instead of based on physiological reference information. For variables where no data are available, no scaling might be applied [7]. These approaches limit the biorelevance and predictive value of absorption simulation and may therefore result in the development of oral drug products for children that have suboptimal drug performance in vivo.…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal Fluid Volumes in Pediatrics: A Retrospective MRI Study

et al. 2022

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The volume and distribution of fluids available in the gastrointestinal (GI) tract may substantially affect oral drug absorption. Magnetic resonance imaging (MRI) has been used in the past to quantify these fluid volumes in adults and its use is now being extended to the pediatric population. The present research pursued a retrospective, explorative analysis of existing clinical MRI data generated for pediatric patients. Images of 140 children from all pediatric subpopulations were analyzed for their resting GI fluid volumes in fasting conditions. In general, an increase in fluid volume as a function of age was observed for the stomach, duodenum, jejunum, and small intestine (SI) as a whole. No specific pattern was observed for the ileum and colon. Body mass index (BMI), body weight, body height, and SI length were evaluated as easy-to-measure clinical estimators of the gastric and SI fluid volumes. Although weight and height were identified as the best estimators, none performed ideally based on the coefficient of determination (R2). Data generated in this study can be used as physiologically relevant input for biorelevant in vitro tests and in silico models tailored to the pediatric population, thereby contributing to the efficient development of successful oral drug products for children.

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Section: Introductionmentioning

confidence: 99%

Gastrointestinal Fluid Volumes in Pediatrics: A Retrospective MRI Study

et al. 2022

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“…In addition to infant and adult HIF, the solubility of the selected compounds was determined in fasted and fed state SIF, designed to mimic adult intestinal fluids. A recent industry survey found that these adult SIF are also used to simulate pediatric drug solubility and dissolution, due to the lack of reference data on the intestinal fluid composition in children 14 . The present data shows that the ability of adult SIF to predict average solubility in infant HIF is highly drug dependent.…”

Section: Solubility In Sif Compared To Average Solubility In Infant Hifmentioning

confidence: 99%

“…Despite significant progress in the predictive in vitro and in silico simulation of drug absorption in preclinical drug development, physiological changes related to disease, medication or age are currently poorly implemented due to the lack of reference data 13 . To advance the development of oral drugs tailored to the paediatric population 14,15 , for instance, recent studies have explored different absorption-related aspects of the gastrointestinal physiology in children, including fluid volume 16,17 , fluid composition 18,19 , and drug transporter and metabolic enzyme ontogeny 20,21 . In addition, Maharaj Pagina 3 van 28 et al 22 designed neonatal and pediatric SIF to explore drug solubility in children.…”

Section: Introductionmentioning

confidence: 99%

Characterization of neonatal and infant enterostomy fluids - part II: Drug solubility

Waal

Brouwers

Rayyan

et al. 2023

International Journal of Pharmaceutics

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“…2 Children are particularly affected by the continuing lack of R&D and quality, safe and effective medicines globally. [3][4][5] To improve paediatric care, the European Union (EU) and the USA introduced paediatric medicines legislation in 2007 and 1997, respectively. This legislation is based on a combination of obligations and incentives.…”

Section: Introductionmentioning

confidence: 99%

Public health relevance of medicines developed under paediatric legislation in Europe and the USA: a systematic mapping study

Volodina,

Jahn,

Jahn

2024

bmjpo

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BackgroundLegislation in the European Union (EU) and the USA promoting the development of paediatric medicines has contributed to new treatments for children. This study explores how such legislation responds to paediatric health needs in different country settings and globally, and whether it should be considered for wider implementation.MethodsWe searched EU and US regulatory databases for medicines with approved indications resulting from completed paediatric development between 2007 and 2018. Of 195 medicines identified, 187 could be systematically mapped to the burden of the target disease for six study countries (Australia, Brazil, Canada, Kenya, Russia, South Africa) and globally, using disability-adjusted life years (DALYs). All medicines were also screened for inclusion on the WHO Model List of Essential Medicines (EML) and the EML for children under 13 years (EMLc).ResultsThe studied medicines were disproportionately focused on non-communicable diseases, which represented 68% of medicines and 21% of global paediatric DALYs. On the other hand, we found 28% of medicines for communicable, maternal, neonatal and nutritional disorders, representing 73% of global paediatric DALYs. Neonatal disorders and malaria were mapped with two medicines, tuberculosis and neglected tropical diseases with none. The gap between medicines and paediatric DALYs was greater in countries with lower income. Still, 34% of medicines are included in the EMLc and 48% in the EML.ConclusionsPaediatric policies in the EU and the USA are only partially responsive to paediatric health needs. To be considered for wider implementation, paediatric incentives and obligations should be more targeted towards paediatric health needs. International harmonisation of legislation and alignment with global research priorities could further strengthen its impact on child health and support ongoing efforts to improve access to medicines. Furthermore, efforts should be made to ensure global access to authorised paediatric medicines.

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Practical and operational considerations related to paediatric oral drug formulation: An industry survey

Cited by 15 publications

References 38 publications

Gastrointestinal Fluid Volumes in Pediatrics: A Retrospective MRI Study

Gastrointestinal Fluid Volumes in Pediatrics: A Retrospective MRI Study

Characterization of neonatal and infant enterostomy fluids - part II: Drug solubility

Public health relevance of medicines developed under paediatric legislation in Europe and the USA: a systematic mapping study

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