Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability

Abstract

The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling. Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10% and 20% w/w of haloperidol using Kollidon VA64, Kollicoat IR, Affinsiol15 cP, and HPMCAS either individually or as binary blends (Kollidon VA64 + Affinisol 15 cP, 1:1; Kollidon VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60% infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon VA64-Affinisol 15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60% and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon VA64 and Affinisol15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release.

Development of 3D Printed Tablets by Fused Deposition Modeling Using Polyvinyl Alcohol as Polymeric Matrix for Rapid Drug Release

“…In addition, printers used for FDM 3D printing have gained popularity among general public for many different applications and can be purchased at a relatively low cost. However, as reviewed earlier by Solanki et al, 12 one limiting factor in the application of the technology for the development of pharmaceutical dosage forms is the relative lack of pharmaceutically acceptable polymers that may be used for FDM 3D printing. Most of the polymers generally used in pharmaceutical dosage forms were originally developed as binders, disintegrants, coating agents, tablet matrices, carriers for solid dispersions, etc.…”

“…Lack of printability, slow or incomplete drug release, and inadequate miscibility between polymer and drug are some of the challenges faced in FDM 3D printing. 12 The extruded filaments of most pharmaceutical grade polymers cannot be printed as they are either too brittle that they break in the motor gear (plunger assembly) of the printer head or too soft that they cannot be pushed by the drive gear due to pliability of filament. 13,14 Even when the polymers can be printed, often by the addition of plasticizers and other additives, 15 the printed tablets may not disintegrate due to extremely low porosity resulting from the fusion of drug and polymeric matrix during melt extrusion and 3D printing.…”

“…21 Because most drugs currently available in the market or new drug candidates that are emerging from the discovery pipeline are very water-insoluble, it is also preferable that the drugs are miscible with polymers used in 3D printing to form ASDs such that their dissolution rates are dependent on the dissolution or erosion of the polymeric matrix and not by the limited drug solubility. 12 Various formulation and geometrical modifications have been reported in the literature to enhance dissolution rate and achieve complete drug release from 3D printed tablets. They include incorporation of highly water-soluble materials in formulations, 16,17,22 increasing porosity by reducing infill in 3D printed tablets, 12 and changing geometry of tablets or forming channels into tablets for relatively rapid fragmentation of tablets.…”

“…12 Various formulation and geometrical modifications have been reported in the literature to enhance dissolution rate and achieve complete drug release from 3D printed tablets. They include incorporation of highly water-soluble materials in formulations, 16,17,22 increasing porosity by reducing infill in 3D printed tablets, 12 and changing geometry of tablets or forming channels into tablets for relatively rapid fragmentation of tablets. 23,24 However, the success of these techniques to increase drug release rate from tablets was mixed and variable.…”

Additive Manufacturing of Precision Biomaterials

“…As, FDM employs relatively high temperatures to melt and then extrude a polymer filament, it is critical that the active pharmaceutical ingredient (API) be stable at elevated temperatures, and that inclusion of the API does not affect significantly the mechanical properties of the filament. It is also important to specify the application and the desired release profile, either rapid or slow release, in order to plan the materials and print path for the tablet properly . One of the first reported studies using FDM to produce pharmaceutical tablets loaded a PVA filament with aminosalicylate isomers by solvent diffusion .…”