Printing of Non-Printable: 3D Printing of Pharmaceutical Oral Solid Dosage Forms by a Fused Deposition Method

3/22/2022 13:55 - 14:25

3D printing (3DP) by fused deposition modelling (FDM) is one of the most extensively developed methods in additive manufacturing. Optimizing printability by improving feedability, nozzle extrusion, and layer deposition is crucial for manufacturing solid oral dosage forms with desirable properties. This work aimed to use brittle HPMCAS polymer (AffinisolTM HPMCAS 716) to prepare filaments for FDM-3DP using hot-melt extrusion (HME). It explored and demonstrated the effect of HME-filament composition and fabrication process on their printability by evaluating thermal, mechanical, and thermo-rheological properties. It also showed the ability of the selected polymer in the HME-filament composition used for FDM-3DP of oral solid dosage forms to provide a tailored drug release profile. HME (HAAKE MiniLab) and FDM-3DP (MakerBot) were used to prepare HME-filaments and printed objects, respectively. Two diverse ways of improving the mechanical properties of HME-filaments were deduced by changing the formulation to enable feeding through the roller gears of the printer nozzle. These include plasticizing brittle polymer and adding insoluble structuring agent such as talc into the formulation. Experimental feedability was predicted using texture analysis results and correlation (R2=0.9827) between bending force, as a function of PEG concentration, and glass-transition temperature (Tg) values of HME-filaments. The effect of HME-filament inhomogeneity on printability, as a function of HME screw speed, was displayed through the inconsistency of the printer nozzle extrudate and printed layers. The high standard deviation of the glass-transition temperature (Tg) and the scanning electron microscopy (SEM) images of nozzle extrudates and lateral wall of the printed tablet supported this result. The melt viscosity of HPMCAS and its formulations was investigated using a capillary rheometer. The high viscosity of unplasticized HPMCAS was concluded to be an additional restriction for nozzle extrusion. The plasticization of brittle polymers and the addition of talc into the formulation were shown to improve the thickness consistency of printed layers (using homogeneous HME-filaments). A good correlation (R2=0.9546) between the solidification threshold (low-frequency oscillation test determined by parallel-plate rheometer) and Tg of HME-filaments was also established. This correlation supported the visual SEM-observation of layer thickness and printed tablet geometry consistency. Drug-loaded and placebo HPMCAS-based formulations were shown to be successfully printed, with the former providing tailored drug release profiles based on variation in internal geometry (infill).

Valentyn Mohylyuk, Pharmaceutical Scientist (research fellow), Queen's University Belfast