The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment

Abstract

Paracetamol-loaded tablets were printed by fused deposition modelling technique, using polyvinyl alcohol as a backbone polymer and Affinisol™ HPMC as a plasticizer in all formulations. Four different strategies were applied in order to accelerate the drug release from the tablets. First, different release enhancers were added: sodium starch glycolate, croscarmellose sodium, Kollidon CL and mannitol. Kollidon CL and mannitol showed the greatest influence on the drug dissolution rate. The second strategy included lowering the infill density, which did not make any significant changes in dissolution profiles, according to the calculated similarity factor. Then the best two release enhancers from the first strategy were combined (Kollidon CL and mannitol) and this proved to be the most effective in the drug release acceleration. The fourth strategy, increasing the percentage of the release enhancers in formulation, revealed the importance of their concentration limits. In summary, the drug release accelerated from 58% released after 5 h to reaching the plateau within 2 h. In silico physiologically-based biopharmaceutics modelling showed that formulations with mannitol and Kollidon CL, especially the formulation containing a combination of these release enhancers, can provide relatively fast drug release and extent of drug absorption that complies with an immediate release tablet.