Research advances in key technologies and real-time quality control for quality by design-driven micrometer-scale tablet formulations
WU Lei
REN Peng-fei
YU Zhou-bo
LI Zhen-bo
HE Yu-xin
LIU Yi-han
YANG Jing
WANG Rui
Abstract：Micron-scale tablets(1 000～3 000 μm),driven by the dual forces of Pharmaceutical Industry 4.0 and precision medicine,have emerged as a core carrier for pediatric and personalized treatment due to their exceptional dose flexibility and multi-unit delivery advantages.The quality by design(QbD)concept provides a systematic framework to overcome key industrialization bottlenecks-such as poor flowability at high drug loads,challenges in achieving blend uniformity for ultra-low-dose formulations,and stringent sensitivity requirements for miniaturized quality control-facilitating the successful establishment of a multidimensional"structure-process-quality"correlation model in the field.Research advances demonstrate that the integration of multimodal spectral imaging(HSI-FT-NIR coupling)with neural network fusion technology enables real-time tracking of content uniformity and release profiles at the millimeter level,facilitating the formation of a full-chain quality control closed-loop from process analysis to dynamic release.The integrated application of innovative technologies such as hot melt extrusion-based microfluidic 3D printing offers new pathways for constructing complex functional dosage forms like colon-targeted and gastric-floating tablets.This review further examines the challenges and breakthrough directions for intelligent upgrades in continuous manufacturing under the QbD framework and outlines interdisciplinary pathways and future prospects for the efficient clinical translation of micron-scale tablet technologies.
Keywords：micron-sized tabletsquality by designcontinuous manufacturingreal-time quality controlIn vitro and in vivo correlationsprocess analytical technologypediatric precision drug delivery3D printing technology
Publication Date：2026-04-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：9( 701-709 )