The publications of the members of Eng4Life.
2026
Caccavo, Diego; Broegg, Luca; Lamberti, Gaetano; De Piano, Raffaella; Barba, Anna Angela
Process-guided design of nanoliposomal vitamin D3: formulation, stability and quality by design mapping Journal Article
In: International Journal of Pharmaceutics, vol. 696, 2026.
Abstract | Links | BibTeX | Tags: Box–Behnken design, Coaxial-jet mixing, nanoliposomes, Quality-by-Design, Vitamin D3
@article{Caccavo2026,
title = {Process-guided design of nanoliposomal vitamin D3: formulation, stability and quality by design mapping},
author = {Diego Caccavo and Luca Broegg and Gaetano Lamberti and De Piano, Raffaella and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/pii/S0378517326002735/pdfft?md5=638132f36776e3d30c7e88f84953e514&pid=1-s2.0-S0378517326002735-main.pdf},
doi = {https://doi.org/10.1016/j.ijpharm.2026.126825},
year = {2026},
date = {2026-05-05},
urldate = {2026-05-05},
journal = {International Journal of Pharmaceutics},
volume = {696},
abstract = {The development of aqueous vitamin D3 supplements remains challenging because the molecule is poorly soluble, chemically fragile, and prone to loss of potency during storage. In this work, we adopted a Quality-by-Design (QbD) strategy to construct a nanoliposomal structure able to protect and deliver vitamin D3 while maintaining technological simplicity and high tolerability. As a first step, drug-free nanoliposomes were produced using a coaxial-jet mixer and systematically investigated through a Box–Behnken Design. This approach allowed us to identify the critical relationships between phosphatidylcholine concentration, solvent/antisolvent flow rates, and the resulting nanoliposomal architecture, thereby defining a robust design space for nano-vesicle formation. Vitamin D3 was then introduced into the optimized system to verify process transferability. Encapsulation proved efficient and compatible with the micromixing-driven assembly of nanoliposomes, and the formulation was subsequently subjected to accelerated and real-time stability studies. These experiments revealed a clear hierarchy of stabilizing effects, highlighting the combined protective role of the liposomal bilayer and a carefully balanced antioxidant environment. Building on these findings, the research formulation was further refined into a commercially viable product, described in a dedicated patent, and benchmarked against leading marketed references. The final dispersion exhibited high structural uniformity, stable vitamin retention and manufacturing features consistent with large-scale implementation. Overall, this work demonstrates how a QbD-guided pathway — from mechanistic process mapping to stability-driven optimization and product translation — can yield a high-quality nanoliposomal vitamin D3 with clear technological and practical advantages.},
keywords = {Box–Behnken design, Coaxial-jet mixing, nanoliposomes, Quality-by-Design, Vitamin D3},
pubstate = {published},
tppubtype = {article}
}
The development of aqueous vitamin D3 supplements remains challenging because the molecule is poorly soluble, chemically fragile, and prone to loss of potency during storage. In this work, we adopted a Quality-by-Design (QbD) strategy to construct a nanoliposomal structure able to protect and deliver vitamin D3 while maintaining technological simplicity and high tolerability. As a first step, drug-free nanoliposomes were produced using a coaxial-jet mixer and systematically investigated through a Box–Behnken Design. This approach allowed us to identify the critical relationships between phosphatidylcholine concentration, solvent/antisolvent flow rates, and the resulting nanoliposomal architecture, thereby defining a robust design space for nano-vesicle formation. Vitamin D3 was then introduced into the optimized system to verify process transferability. Encapsulation proved efficient and compatible with the micromixing-driven assembly of nanoliposomes, and the formulation was subsequently subjected to accelerated and real-time stability studies. These experiments revealed a clear hierarchy of stabilizing effects, highlighting the combined protective role of the liposomal bilayer and a carefully balanced antioxidant environment. Building on these findings, the research formulation was further refined into a commercially viable product, described in a dedicated patent, and benchmarked against leading marketed references. The final dispersion exhibited high structural uniformity, stable vitamin retention and manufacturing features consistent with large-scale implementation. Overall, this work demonstrates how a QbD-guided pathway — from mechanistic process mapping to stability-driven optimization and product translation — can yield a high-quality nanoliposomal vitamin D3 with clear technological and practical advantages.