Selective laser sintering (SLS) 3D printing is capable of revolutionising pharmaceutical manufacturing, by producing amorphous solid dispersions in a one-step manufacturing process. Here, 3D-printed formulations loaded with a model BCS class II drug (20% w/w itraconazole) and three grades of hydroxypropyl cellulose (HPC) polymer (-SSL, -SL and -L) were produced using SLS 3D printing. Interestingly, the polymers with higher molecular weights (HPC-L and -SL) were found to undergo a uniform sintering process, attributed to the better powder flow characteristics, compared with the lower molecular weight grade (HPC-SSL). XRPD analyses found that the SLS 3D printing process resulted in amorphous conversion of itraconazole for all three polymers, with HPC-SSL retaining a small amount of crystallinity on the drug product surface. The use of process analytical technologies (PAT), including near infrared (NIR) and Raman spectroscopy, was evaluated, to predict the amorphous content, qualitatively and quantitatively, within itraconazole-loaded formulations. Calibration models were developed using partial least squares (PLS) regression, which successfully predicted amorphous content across the range of 0–20% w/w. The models demonstrated excellent linearity (R² = 0.998 and 0.998) and accuracy (RMSEP = 1.04% and 0.63%) for NIR and Raman spectroscopy models, respectively. Overall, this article demonstrates the feasibility of SLS 3D printing to produce solid dispersions containing a BCS II drug, and the potential for NIR and Raman spectroscopy to quantify amorphous content as a non-destructive quality control measure at the point-of-care.

Zero-order release formulations are designed to release a drug at a constant rate over a prolonged time, thus reducing systemic side effects and improving patience adherence to the therapy. Such formulations are traditionally complex to manufacture, requiring multiple steps. In this work, fused deposition modeling (FDM) 3D printing was explored to prepare on-demand printlets (3D printed tablets). The design includes a prolonged release core surrounded by an insoluble shell able to provide zero-order release profiles. The effect of drug loading (10, 25, and 40% w/w paracetamol) on the mechanical and physical properties of the hot melt extruded filaments and 3D printed formulations was evaluated. Two different shell 3D designs (6 mm and 8 mm diameter apertures) together with three different core infills (100, 50, and 25%) were prepared. The formulations showed a range of zero-order release profiles spanning 16 to 48 h. The work has shown that with simple formulation design modifications, it is possible to print extended release formulations with tunable, zero-order release kinetics. Moreover, by using different infill percentages, the dose contained in the printlet can be infinitely adjusted, providing an additive manufacturing route for personalizing medicines to a patient.