Making Medicines Baby Size: The Challenges in Bridging the Formulation Gap in Neonatal Medicine

Abstract

The development of age-appropriate formulations should focus on dosage forms that can deliver variable yet accurate doses that are safe and acceptable to the child, are matched to his/her development and ability, and avoid medication errors. However, in the past decade, the medication needs of neonates have largely been neglected. The aim of this review is to expand on what differentiates the needs of preterm and term neonates from those of the older paediatric subsets, in terms of environment of care, ability to measure and administer the dose (from the perspective of the patient and carer, the routes of administration, the device and the product), neonatal biopharmaceutics and regulatory challenges. This review offers insight into those challenges posed by the formulation of medicinal products for neonatal patients in order to support the development of clinically relevant products.

Medicamentos não licenciados: uma discussão em pediatria

“…Além dos fármacos e excipientes que estão contidos nos medicamentos que passarão pelo processo de reformulação, também são adicionados novos excipientes que devem ter bons parâmetros de funcionalidade, segurança e qualidade. Ainda que os excipientes sejam farmacologicamente inertes, esses não estão isentos de provocar riscos aos pacientes (Goes et al, 2019;O'Brien et al, 2019).…”

“…Embora a maioria dos estudos cite os riscos do uso de medicamentos não licenciados na pediatria, poucos abordaram os perigos da escolha inapropriada de excipientes para a nova formulação. Não obstante, é importante destacar que certos excipientes devem ser evitados na preparação de medicamentos para crianças, pois podem provocar prejuízo no desenvolvimento de órgãos e sistemas, como, por exemplo, o etanol, o propilenoglicol, o álcool benzílico e os parabenos (Batchelor & Marriott, 2015;O'Brien et al, 2019).…”

Approaches to Dose Finding in Neonates, Illustrating the Variability between Neonatal Drug Development Programs

“…Finally, the need for dose accuracy in (pre)term neonates necessitates an additional focus on age-appropriate formulations [3]. When applied to some drugs considered in this review, oral doses were prepared extemporaneously including up to 1:99 dilutions for clopidogrel, and the mg/mL dose of surfactant differs between different formulations, while there are currently different caffeine (strength) formulations registered in Europe (10 or 20 mg/mL) [59,60].…”

“…As a consequence, dosing regimens in neonates have been based on trial and error from non-neonatal indications primarily studied in adult medicine and are purely based on the pathophysiology in adults [1,2]. In addition to dosing, formulations or dosage forms should be tailored to deliver accurate and safe doses in (pre)-term neonates as their specific needs have recently been summarized [3].…”

Paediatric Formulation: Design and Development

“…In this Special Issue, O’Brien at al. [ 22 ] published a review that offered insight into those challenges posed by the formulation of medicinal products for neonatal patients in order to support the development of clinically valid products. Neonates cannot be classified as small children when it comes to medicinal products and their formulation development.…”