Pediatric drug development: formulation considerations

Abstract

Absence of safe, effective and appropriate treatment is one of the main causes of high mortality and morbidity rates among the pediatric group. This review provides an overview of pharmacokinetic differences between pediatric and adult population and their implications in pharmaceutical development. Different pediatric dosage forms, their merits and demerits are discussed. Food and Drug Administration Act of 1997 and the Best Pharmaceuticals for Children Act 2002 added 6 months patent extension and exclusivity incentives to pharmaceutical companies for evaluation of medicinal products in children. Prescription Drug User Fee Act and Food and Drug Administration Amendments Act of 2007 made it mandatory for pharmaceutical companies to perform pediatric clinical studies on new drug products. Drug development program should include additional clinical bridge studies to evaluate differences in pharmacokinetics and pharmacodynamics of drugs in adult and child populations. Additionally, pharmaceutical development should consider ease of administration, palatability, appropriate excipients, stability and therapeutic equivalency of pediatric dosage forms. Pediatric population is diverse with individual preferences and demand for custom made dosage formulations. Practically it is not feasible to have different pharmaceutical dosage forms for each group. Hence, an appropriate dosage form that can be administered across pediatric population is warranted.

Buccal Dosage Forms: General Considerations for Pediatric Patients

“…Clearance values obtained by scaling to body surface area do not require height measurement; (B) using the body surface area, which assumes a proportionality with physiological processes; however, the large number of formulas to calculate body surface area makes this estimation difficult and may lead to several errors but is more secure than body weight dosing (47); (C) normalization of a dose to body weight may have problems with pharmacokinetic parameters due to the differences in pediatric clearance that can be altered compared with adult clearance; the difference of this strategy with the allometric scaling is that this method does not consider factors such as obesity and differences in clearance for certain drugs to calculate the body surface area leading to a possible overdose (46); and (D) classifying the patient into an agebased category to see the recommended doses; however, these could result in a bad approach due to the pharmacokinetic variability (48). Knowing these four types of methods, the dose for a buccal administration can be calculated by methods B, C, and/or D but it has to be mentioned that to avoid all the potential errors mentioned above, it is imperative to extend the investigation and development of dosage forms, considering that pharmacokinetics are not the same over the range of ages enclosed in the "pediatric" term (49). For instance, the plasma concentration of pediatric patients can easily be four to five times higher than adults due to their small volume of distribution, heart rate, and reduced blood pressure (13,50).…”

Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome

“…Nowadays, methadone and phenobarbital are marketed in pharmaceutical forms not suitable for pediatric population. Many medicinal products are not currently available in formulations suitable for administration to the pediatric population 12 . Nearly 75% of the drugs available in the USA for adults have not been labeled for use in infants and children, even though these drugs may be needed in this population 13 .…”

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation

“…Antimicrobial preservatives, suspending agents, and flavoring agents are widely used in pediatric formulations. The selected excipients in pediatric formulations should be safe and stable 13 . Excipients are an integral part of a completed pharmaceutical product; therefore, the safety and the quality of medicines depend not only on the active principles and production processes but also the safety and performance of excipients.…”