Challenges, current status and emerging strategies in the development of rapidly dissolving FDM 3D-printed tablets: An overview and commentary

Abstract

Since the approval of a 3D-printed tablet by the FDA in 2015 for marketing, there has been a great interest in 3D printing in the pharmaceutical field for the development of personalized and on-demand medications. Among various 3D printing methods explored for the development of oral solid dosage form like tablet, the fused deposition modeling (FDM) 3D-printing, where the drug-polymer mixtures are first converted into filaments by hot melt extrusion (HME) and then the filaments are printed into tablets using 3D printers by applying computer-aided design principles, has emerged as the most attractive option. However, no FDM 3D-printed tablets have yet been marketed as the technology faces many challenges, such as limited availability of pharmaceutical-grade polymers that can be printed into tablets, low drug-polymer miscibility, the need for high temperature for HME and 3D-printing, and slow drug release rates from tablets. These challenges are discussed in this article with a special focus on drug release rates since FDM 3D-printing usually leads to the preparation of slow-release tablets while the rapid release from dosage forms is often desired for optimal therapeutic outcomes of new drug candidates. Pros and cons of various strategies for the development of rapidly dissolving FDM 3D-printed tablets reported in the literature are reviewed. Finally, two case studies on emerging strategies for the development of rapidly dissolving FDM 3D-printed tablets are presented, where one outlines a systematic approach for formulating rapidly dissolving tablets, and the other describes a novel strategy to increase dissolution rates of drugs from FDM 3D-printed tablets, which at the same time can also increase drug-polymer miscibility and printability of tablets and lower processing temperatures. Thus, this overview and commentary discusses various issues involving the formulation of rapidly dissolving FDM 3D-printed tablets and provides guidance for the development of commercially viable products.

Status of Polymer Fused Deposition Modeling (FDM)-Based Three-Dimensional Printing (3DP) in the Pharmaceutical Industry

“…On the other hand, an increased API content modifies the crystallographic, thermal and rheological properties of the filament, with the possibility of rendering them unprintable [116]. Since FDM is a mechanical process, failure within moving parts can affect the printing process [117]. Crucially, there is only a handful of suitable thermoplastic polymers suited for use in FDM 3DP pharmaceutical dosage forms [72].…”

Geometry-Driven Fabrication of Mini-Tablets via 3D Printing: Correlating Release Kinetics with Polyhedral Shapes

“…The main method for preparing drug-loaded filaments for use in typical FDM 3D printers is hot melt extrusion (HME) technology. In the HME process, active pharmaceutical ingredients (APIs) are blended with thermoplastic polymers, melted below their glass transition temperature, and subsequently extruded by screws in the HME [ 13 , 14 ]. There are several challenges faced during the preparation of drug-loaded filaments for HME and commercial 3D printing; for example, the original filaments, available for commercial 3D printing, are mainly composed of acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA).…”

Dissolution-permeation of hot-melt extruded amorphous solid dispersion comprising an experimental grade of HPMCAS

“…Commercial products of solid dispersion prepared by hot-melt extrusion can comprise various polymeric carriers [8]. Polyvinylpyrrolidone, copovidone, and cellulosic polymers are widely used in commercially and in research [8][9][10][11][12]. Studies on polymeric carriers revealed that hydroxypropyl methylcellulose acetate succinate (HPMCAS) has better physical stability and oral absorption than other carriers [13][14][15] and is used in a commercial product, "Noxafil  ".…”