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.

Keywords: 3D printing; 3D-printed tablet; drug release; fused deposition modeling; hot melt extrusion; rapid dissolution.

Figure 1.

(A) Illustration of melt extrusion of filaments and 3D-printing of tablets during the FDM 3D-printing process. (B) Printing gear, nozzle, and printing plate are shown with an expanded scale. Adapted from Ilyes et al. [22] with permission.

Figure 2.

Four scenarios of drug product development according to the Biopharmaceutical Roadmap (BioRAM). Adapted from Selen et al. [17] with permission.

Figure 3.

Different methods of increasing surface area by modifying tablet patterns and geometry: I, changing tablet infill; II, geometric modification by connecting blocks of fill materials; III, introduction of perforated channels; and IV, connection of parallel plates in a radiator-like design.

Figure 4.

Graphical illustration of acid-base supersolubilization (ABS) principle for a basic drug, where Graph I (top) represents a typical pH versus solubility profile resulting in salt formation at low pH, and Graph 2 (bottom) shows a high increase in solubility (supersolubilization) with lowering of pH when no salt is formed by the addition of a weak acid.

Figure 5.

Systematic approach for the identification of polymers for the development of rapidly dissolving FDM 3D-printed tablets.

Figure 6.

Dissolution of haloperidol from FDM 3D-printed tablets containing 10 % drug load in 1:1 Kollidon® VA64-Affinisol® 15 cP mixtures and having 100 % and 60 % infill densities at pH 2 and 6.8.

Figure 7.

Effects acid-base interaction between glutaric acid and haloperidol on melt extrusion and printing temperatures, printability, and drug-polymer miscibility of FDM 3D printed tablets.

Figure 8.

Dissolution of haloperidol from FDM 3D-printed tablets containing 15 % drug load from a formulation containing 1:2 molar ratio of drug to glutaric acid and having 100 % and 60 % infill densities at pH 2 and 6.8. Kol, Hal and GA represent Kollidon® VA64, haloperidol, and glutaric acid.