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

利用选择性激光烧结(SLS)3D打印技术对载利福平的3D打印片剂进行药代动力学评估和A级体内外相关性(IVIVC)建立

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Abstract

BACKGROUND: This study investigated the in vitro dissolution and in vivo absorption of rifampicin (RIF)-containing 3D-printed tablets using Selective Laser Sintering (SLS) technology. METHODS: In vitro dissolution was assessed in acidic (pH 1.2) and alkaline (pH 6.8) buffer media, while in vivo 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. RESULTS: 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 C(max) (445.38 ± 193.62 ng/mL), T(max) (02 ± 0.00 hr), AUC(0-t) (841.51 ± 334.13 ng.h/mL), AUC(0-∞) (861.66 ± 340.54 ng.h/mL), K(el) (0.61 ± 0.13 h(-1)), and t(1/2) (1.18 ± 0.25 hr) were obtained, demonstrating effective RIF absorption in the rabbit. Additionally, an in vitro-in vivo correlation (IVIVC) model was developed, demonstrating a good correlation between in vitro release and in vivo absorption, with R(2) value of 0.9696. CONCLUSION: The results underscore the potential of SLS 3DP technology in advancing the development of RIF-containing 3D printed tablets by sustaining in vitro dissolution following in vivo absorption profiles.

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