Pediatric medications require dose flexibility to obtain desired therapeutic concentration. Most medications are produced
for adults as capsules and tablets, which are often not suitable for children. The lack of or limited availability of medications
for the pediatrics population is primarily due to the evolving physiology of children where fixed dosage forms do not work.
Extemporaneous formulations are a common way to adjust the dose of the drug for pediatrics patient. However, concerns
have been raised regarding lack of dose accuracy, stability, bioavailability and consistency for such formulations by
healthcare professionals and FDA. Quality, safety and efficacy concerns of extemporaneous preparations can be addressed
by printing medications by selective laser sintering (SLS) 3D printing method as supported by preliminary data. The SLS
method is ideally suited to print precision dosage forms in a clinical hospital environment, and has dose-flexibility, multiple
drug incorporation capability, short-time to print, minimal material requirement, low-power needs, and small footprint of
the equipment. Doses can easily be adjusted by number of printed layer since printing is performed by layering mechnaism.
The objective of the proposal is to demonstrate the feasibility of printing dose-flexible pediatric delivery system (printlets)
using selective laser sintering (SLS). Tenofovir disoproxil fumarate and lamivudine will be used as model drugs, as both
drugs are commonly used alone or in combination in pediatric patients. However, only a single strength combination product
(of both drugs) is commercially available. Administering these drugs as age appropriate flexible pediatric delivery systems
will reduce overdose and underdose, which is the case with extemporaneous preparation intended for pediatric population.
This would be translated into lower incidence of adverse events and reduce probability of development of HIV resistance
to medications when underdose. Furthermore, dose-flexible pediatric delivery systems should meet quality criteria of FDA,
and should be stable during shelf-life and usage periods besides being effective. The delivery systems will be tested as per
FDA and USP recommended tests to ensure quality. Pediatric delivery systems will be tested for long-term, accelerated and
in-use stability conditions. Safety and efficacy will be demonstrated by comparative pharmacokinetics and
pharmacodynamics studies between dose flexible pediatric delivery system and commercial tablets formulation. The PI of
the proposal led the FDA team of scientists and reviewers to the approval of the first and only 3D printed drug product
(Spritam®). Following are the specific aims of the proposal:
Aim I: To demonstrate the feasibility of printing pediatric delivery systems (printlets) of combination drugs (tenofovir
disoproxil fumarate and lamivudine) by selective laser sintering in short timeframes (<2 hours), characterize the quality
and assess stability that will meet United States Pharmacopeia (USP) and Food and Drug Administration (FDA)
requirements of identity, quality, purity, and strength.
Aim II: To demonstrate the safety and efficacy of flexible pediatric delivery systems (printlets) by pharmacokinetics and