Formulation and characterisation of dual compartments 3d-printed tablets containing isoniazid and pyridoxine using hot-melt extrusion and fused deposition modelling

Abstract

Patients on isoniazid (INH) should be given daily prophylactic pyridoxine (PYR) at 10-50 mg/day to prevent the development of isoniazid-induced neuropathy. One of the factors that make patients less compliant with tuberculosis (TB) drugs is polypharmacy. Since a 3D-printed technology can accommodate a high-loaded dosage form, it can reduce the amount of INH and PYR tablets taken daily by combining both tablets as a single tablet. This study's first objective was to simultaneously determine INH and PYR in pure form and 3D-printed tablet dosage form and wholly validate it by analytical method validation (AMV) of UV-Vis spectroscopy. The results demonstrated that it was specific, linear, accurate, precise, and sensitive. Moving to the second objective, the study formulated ten formulations that included blanks and INH-loaded filaments, as well as three additional formulations of PYR-loaded filaments utilising hot-melt extrusion (HME). Then, all the extruded filaments were characterised by using differential scanning calorimetry (DSC), ATR-Fourier transforms infrared spectroscopy (FTIR), and moisture uptake before formulation INH-5 and formulation PYR-3 were selected to be printed by the fused deposition modeling (FDM) subsequently. The dual compartments of 3D-printed tablets were successfully printed by putting the PYR 3D-printed tablet at the top while the INH 3D-printed tablet at the bottom part. The third objective of this research was post-printing parameters such as weight variation, diameters, thickness, hardness, friability, disintegration time, dissolution time, and drug content studies for the dual compartments of 3D-printed tablets containing INH and PYR were found to comply with British Pharmacopoeia (BP), except for disintegration and dissolution time of INH 3D-printed tablet part. The bilayer INH/ PYR 3D-printed tablets can be classified as a controlled-release drug delivery system based on their dissolution profile. Drug release characteristics could be further adjusted by modifying the infill density to a lower percentage or adding disintegrant aids such as binders or fillers to accelerate the dissolution time.