Development of Advanced 3D-Printed Solid Dosage Pediatric Formulations for HIV Treatment

The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatabil...

Full description

Bibliographic Details
Authors: Malebari, Azizah M.; Kara, Aytug; Khayyat, Ahdab N.; Mohammad, Khadijah A.; Serrano López, Dolores Remedios
Format: Article
Publication date:2022
Country:España
Institution:Universidad Complutense de Madrid (UCM)
Repository:Docta Complutense
Language:English
OAI Identifier:oai:docta.ucm.es:20.500.14352/72526
Online Access:https://hdl.handle.net/20.500.14352/72526
Access Level:Open access
Keyword:pediatric formulation
ritonavir
lopinavir
minitablet
3D printing
direct powder extrusion
HIV
FDM
HME
Inmunología
Pediatría
Farmacología (Farmacia)
2412 Inmunología
3201.10 Pediatría
3209 Farmacología
Description
Summary:The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatability for ritonavir-boosted lopinavir syrup. In addition, the administration of crushed tablets has shown a detriment for the oral bioavailability of both drugs. Therefore, there is a clinical need to develop safer and better formulations adapted to children’s needs. This work has demonstrated, for the first time, the feasibility of using direct powder extrusion 3D printing to manufacture personalized pediatric HIV dosage forms based on 6 mm spherical tablets. H-bonding between drugs and excipients (hydroxypropyl methylcellulose and polyethylene glycol) resulted in the formation of amorphous solid dispersions with a zero-order sustained release profile, opposite to the commercially available formulation Kaletra, which exhibited marked drug precipitation at the intestinal pH.