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.

Keywords: NICU; administration; biopharmaceutics; device; dosage form; excipient; formulation; formulation development; inhaled; intra nasal; medication error; neonates; oral; parenteral; product development; topical.

Figure 1

Schematic of NICU support for neonate (used with permission of Mayo Foundation for Medical Education and Research, all rights reserved).

Figure 2

Newborn child with uncoated mini-tablet in the cheek pouch before swallowing (with permission to use from Thabet et al. 2018 [132]).

Figure 3

Different types of connectors (adapted from IV Sets and Access Devices Product Catalog—B. Braun Medical Inc., effective August 2017).

Figure 4

Example of venous access and multiple drug administration devices.

Figure 5

Photograph illustrating the method of aerosol administration to a sleeping infant showing the Respimat inhaler, InspiraChamber and SootherMask. (reproduced from [160] with permission from BMJ Publishing Group Ltd.).