Single-step Sintered 3D-printed Fixed-dose Combined Bilayer Tablets for Compartmentalized Delivery of First-line...

The bioavailability of Rifampicin (RIF) in fixed-dose combination (FDC) with Isoniazid (INH) poses a significant challenge in tuberculosis therapy due to RIF's rapid degradation under gastric conditions when co-administered with INH, resulting in subtherapeutic plasma levels and compromised therapeutic efficacy. To overcome this issue, we developed a novel Selective Laser Sintering (SLS)-mediated 3D printing approach using SmartEx QD 100 and Eudragit L 100-55 polymers. This advanced technique enabled the fabrication of compartmentalized FDC 3D printed bilayer tablets, designed to release INH in the stomach and RIF in the intestine, thereby preserving RIF stability while maintaining synergistic drug action. The bilayer tablets met pharmacopeial standards for dimensional accuracy, weight variation, friability, and hardness, with adequate tensile and shear strength for ease of handling. Micro-CT and SEM-EDX analysis confirmed uniform pore formation, drug distribution, and successful interlayer fusion. In vitro dissolution demonstrated complete release of INH within 45 min in the gastric region, while RIF exhibited minimal release in the gastric environment and sustained release in the intestinal region. Pharmacokinetic studies in New Zealand white rabbits indicated INH and RIF achieved respective C_max values of 432.00 ± 109.16 ng/mL and 84.57 ± 43.79 ng/mL, with distinct T_max profiles supporting compartmentalized release. This study concludes with the transformative potential of SLS-mediated 3D printing in developing personalized, stable, and effective anti-tuberculosis therapies. By ensuring precise compartmentalized drug delivery, this innovation enhances treatment outcomes, improves patient compliance, and offers a promising platform for future advancements in complex drug delivery systems.