Development of FDM 3D-printed tablets with rapid drug release, high drug-polymer miscibility and reduced printing temperature by applying the acid-base supersolubilization (ABS) principle

Some of the major issues with the development of FDM 3D printed tablets are slow drug release, lack of drugpolymer miscibility, high processing temperature, and poor printability. In this investigation, these issues were addressed by using a novel physicochemical principle called acid-base supersolubilization (ABS) previously developed in our laboratory. The aqueous solubility of a basic drug, haloperidol, was increased to similar to 300 mg/g of solution by adding glutaric acid, and, upon drying, the concentrated solutions produced amorphous materials. Similar amorphous systems could also be produced by heating haloperidol-glutaric acid mixtures. Filaments for 3D printing were prepared by melt extrusion of formulations containing 15% w/w haloperidol and 10.5% glutaric acid (1:2 M ratio) along with 74.5% polymers, such as Kollidon (R) VA64 alone or its mixtures with Affinisol (TM) 15cP. Filaments could be extruded and printed at low temperatures of 115 and 120 degrees C, respectively. Haloperidol was fully miscible in the formulations because of the acid-base interaction and formed amorphous systems even at higher drug loads. Although filaments of haloperidol-Kollidon (R) VA64 mixtures by themselves cannot be printed, the printability of formulation improved such that those containing glutaric acid were printable. Drug release rates from the formulations at pH 2 and 6.8 were rapid and complete.