Dose-independent drug release from 3D printed oral medicines for patient-specific dosing to improve therapy safety.

ABSTRACT

Fused deposition modelling (FDM) 3D printing provides the ability to address individual patients' therapeutic needs without having to change the formulation every time. This is particularly interesting for dosing and release modelling. In this study, a geometry model was developed that can represent variable dosages while keeping the surface area to volume (SA/V) ratio alike, so the drug release profiles remain similar. The model was tested on three different formulations. Two BCS I active pharmaceutical ingredients (API), pramipexole and levodopa, and one BCS II API, praziquantel, were used. Polyvinyl alcohol (PVA, water soluble) and a combination of vinylpyrrolidone-vinyl acetate copolymer (PVP-VA, water soluble) and ethylene-vinyl acetate (EVA, water insoluble) were used as the polymer matrix. The curves were compared using the similarity factor (f2 value) and mean dissolution time (MDT). Using a hollow cylinder-based (HCb) geometry model, a dose-independent drug release could be realized. For the PVA formulations, an 8-fold dose change could be obtained and for the EVA-PVP-VA formulation a factor of 5.5 could be achieved, with f2 > 50. Due to the layer structure of the printed objects, very fine dose variation of 0.13 mg per layer is possible within these models. This allows variable dosing in small steps with only one basis formulation.