3D Printing of Bilayer Tablets: A Comprehensive Review of Technologies, Formulations, and Applications

Abstract

Bilayer tablets represent an advanced oral dosage form enabling the combination of two distinct drug layers within a single unit, facilitating improved drug delivery, reduced dosing frequency and enhanced patient compliance. Conventional manufacturing of bilayer tablets by compression faces significant challenges, including cross-contamination, layer delamination, and limited design flexibility. Three-dimensional (3D) printing has emerged as a transformative technology in pharmaceutical manufacturing, offering unprecedented control over tablet geometry, drug loading and release kinetics. This review comprehensively examines the application of 3D printing technologies, Fused Deposition Modelling (FDM), Selective Laser Sintering (SLS) and Semi-Solid Extrusion (SSE) for the fabrication of 3D printing bilayer tablets. Key topics addressed include: the operating principles and comparative advantages of each technique; polymers and excipients employed in 3D-printed bilayer formulations; clinical applications across tuberculosis management cardiovascular, pain management, and respiratory indications; and future perspectives including artificial intelligence-assisted formulation design and continuous manufacturing integration. 3D printing offers a compelling pathway toward personalized, on-demand pharmaceutical manufacturing of complex bilayer dosage forms.