3D printed bilayer tablet with dual controlled drug release for tuberculosis treatment

In this study Fusion Deposition Modelling (FDM) was employed to design and fabricate a bilayer tablet consisting of isoniazid (INZ) and rifampicin (RFC) for the treatment of tuberculosis. INZ was formulated in hydroxypropyl cellulose (HPC) matrix to allow drug release in the stomach (acidic conditions) and RFC was formulated in hypromellose acetate succinate (HPMC - AS) matrix to allow drug release in the upper intestine (alkaline conditions). This design may offer a better clinical efficacy by minimizing the degradation of RFC in the acidic condition and potentially avoid drug-drug interaction. The bilayer tablet was prepared by fabricating drug containing filaments using hot melt extrusion (HME) coupled with the 3D printing. The HME and 3D printing processes were optimised to avoid drug degradation and assure consistent deposition of drug-containing layers in the tablet. The in-vitro drug release rate was optimised by varying drug loading, infilling density, and covering layers. Greater than 80% of INZ was released in 45 mins at pH 1.2 and approximately 76% of RFC was releases in 45 mins after the dissolution medium was changed to pH 7.4. The work illustrated the potential application of FDM technology in the development of oral fixed dose combination for personalised clinical treatment.