Feasibility of high melting point hydrochlorothiazide processing via cocrystal formation by hot melt extrusion paired fused filament fabrication as a 3D-printed cocrystal tablet

The development of amorphous solid dispersions (ASDs) of high-melting-point drug substances using hot-melt extrusion (HME) continues to be challenging because of the limited availability of polymers that are stable at high processing temperatures. The main aim of this research project is to improve processability and develop three-dimensional (3D) cocrystal printlets of hydrochlorothiazide (HCTZ) using HME paired fused deposition modeling (FDM) techniques. Among the investigated coformers, nicotinamide (NIC) was identified as a suitable coformer. The cocrystal filaments of HCTZ-NIC and pure HCTZ that were suitable for the FDM 3D-printing process were developed using a Process 11 mm Twin-Screw Extruder with Kollicoat (R) IR and Kollidon (R) VA64 as polymeric carriers. The investigation of extruded filaments using differential scanning calorimetry (DSC) revealed the formation of HCTZ-NIC cocrystals, which was further confirmed using Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction analysis (PXRD). The 3D-printed printlets of HCTZ-NIC with 50 % infill density resulted in improved dissolution and permeability compared to pure drug. This demonstrates the suitability of the HME-paired FDM 3D-printing technique for improving solubility and devel-oping on-demand patient-focused dosage forms for poorly soluble high-melting-point drug substances by uti-lizing a cocrystal approach.