ScholarWorks@중앙대학교

초록

Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis, which was developed as an oral dosage form. This study aimed to develop a 3D-printed expandable drug delivery system of tofacitinib and characterize the in vivo pharmacokinetics in beagle dogs. The expandable drug delivery system consisted of a 3D-printed capsular device designed to expand in the stomach and a sustained-release (SR) tablet of tofacitinib. Once in the stomach, the capsular device could be expanded and release the drug from the inner SR tablet within the stomach. After completion of drug release, the capsular device loses the expanding structure and is designed to move to the small intestine. Mixture design was applied to determine the gastric residence time of the expandable drug delivery system with the formulation compositions of the inner IR and SR tablets as control factors. While the capsular device was fabricated by fused deposition modeling (FDM) 3D printer, inner tablets were prepared by conventional wet granulation methods. The prepared expandable drug delivery system was orally administered to beagle dogs and the plasma concentrations of tofacitinib were determined using a validated LC-MS/MS. Following oral administration in beagle dogs, while the tofacitinib SR tablet showed the maximum plasma concentration (Cmax) after 2 h, the expandable system maintained stable plasma concentration up to 8 h. The area under the plasma concentration vs. time curve (AUC) was 752.8 ± 92.6 ng*h/mL for the SR tablet and 515.0 ± 130.3 ng*h/mL for the expandable system. The 3D-printed capsular device may provide a promising tool to develop novel controlled-release dosage forms with an optimized pharmacokinetics and therapeutic efficacy