Pharmacokinetic assessment and level-A IVIVC establishment of rifampicin-loaded 3D printed tablets using SLS 3D printing

This study investigated the <i>in vitro</i> dissolution and <i>in vivo</i> absorption of rifampicin (RIF)-containing 3D-printed tablets using Selective Laser Sintering (SLS) technology. <i>In vitro</i> dissolution was assessed in acidic (pH 1.2) and alkaline (pH 6.8) buffer media, while <i>in vivo</i> absorption was evaluated in a New Zealand White rabbit model. Both analytical and bioanalytical methods were rigorously developed and validated using LC-ESI-MS/MS, following ICH Q2 (R1) and FDA guidelines, respectively. In the acidic medium, 16.22% of RIF was released within the first 2 h, whereas in the alkaline medium, the release increased to 41.75%, indicating a sustained release from the sintered 3D printed tablets. Pharmacokinetic parameters and their corresponding values of <i>C</i>_<i>max</i> (445.38 ± 193.62 ng/mL), <i>T</i>_<i>max</i> (02 ± 0.00 hr), <i>AUC</i>_<i>0-t</i> (841.51 ± 334.13 ng.h/mL), <i>AUC</i>_<i>0-∞</i> (861.66 ± 340.54 ng.h/mL), <i>K</i>_<i>el</i> (0.61 ± 0.13 h⁻¹), and <i>t</i>_<i>1/2</i> (1.18 ± 0.25 hr) were obtained, demonstrating effective RIF absorption in the rabbit. Additionally, an <i>in vitro-in vivo</i> correlation (IVIVC) model was developed, demonstrating a good correlation between <i>in vitro</i> release and <i>in vivo</i> absorption, with R² value of 0.9696. The results underscore the potential of SLS 3DP technology in advancing the development of RIF-containing 3D printed tablets by sustaining <i>in vitro</i> dissolution following <i>in vivo</i> absorption profiles.