Title : Fabrication, characterization, and evaluation of pyrazinamide-loaded immediate-release tablets via fused deposition modeling 3D printing for personalized tuberculosis treatment
Abstract:
Purpose: Paediatric tuberculosis (TB) treatment is challenged by the need for age-appropriate dosage forms, flexible dose adjustment, and improved patient adherence. Three-dimensional (3D) printing has become an attractive technology for the production of customized drugs that can meet specific patient needs. The main objective of the present study was to develop, design and evaluate a personalized multidrug fixed-dose combination (FDC) oral tablet device of isoniazid (INH), pyrazinamide (PZA), and rifampicin (RIF) using hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing technology.
Methods: INH, PZA, polyvinyl alcohol (PVA), and sorbitol were mixed into filaments and loaded with the drug, which were then printed using an FDM 3D printer and used to create compartmentalized tablet devices. The tablet architecture was developed to optimize ease of individual dosing and mechanical strength and dimensional uniformity. The printability, physicochemical properties, drug content uniformity, thermal behaviour, solid-state characteristics, surface morphology, and in vitro drug release performance were characterized in the fabricated formulations.
Results: The 3D printed tablet devices produced were highly printable, dimensionally reproducible, possessed sufficient mechanical strength, low friability, and uniform drug distribution. The DSC and X-ray diffraction studies indicated that the drug molecules were partially amorphized and effectively dispersed in the polymer matrix. The scanning electron microscopy revealed well defined layer deposition with open internal structure, which allowed fast penetration of dissolvent media. The in vitro dissolution test revealed that the incorporated anti-tubercular drugs were released rapidly and reproducible with more than 90% cumulative drug release within the stipulated period. In addition, the formulations retained their physical integrity and drug content during the stability study, demonstrating good formulation stability.
Conclusion: The results show that HME-assisted FDM 3D printing is a potential method for manufacturing immediate-release tablets with pyrazinamide, which exhibits acceptable mechanical strength, a high drug release rate, and good quality. This technology has great potential for the creation of personalized anti-tubercular drugs; however, more long-term stability studies are needed to ensure product shelf-life.
Keywords: Paediatric Tuberculosis, Personalized Medicine, 3D Printing, Fused Deposition Modeling, Hot-Melt Extrusion, Evaluation.
