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. 2025 Mar 28;17(4):432.
doi: 10.3390/pharmaceutics17040432.

Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC

Namhyuck Kim  1 , Kyoungho Kim  1 , Seungwei Jeong  1 , Jiyeong Kim  1 , Helen Cho  1 , Young-Joo Lee  2   3 , Sangyeob Park  1
Affiliations

Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC

Namhyuck Kim et al. Pharmaceutics. .

Abstract

Objectives: This study explores the development and evaluation of a bilayer sustained-release (SR) tablet formulation of ruxolitinib. As a BCS Class 1 drug, ruxolitinib requires twice-daily dosing due to its short half-life. We designed a bilayer tablet that integrates immediate-release (IR) and SR components in varying ratios to achieve sustained plasma concentrations, which we evaluated using discriminative analysis. Methods: Bilayer tablets combining IR and SR components were prepared in different ratios. In vitro dissolution tests and pharmacokinetic studies were conducted using Beagle dogs, followed by the evaluation of in vivo-in vitro correlation (IVIVC), along with a discriminative pharmacokinetic analysis focused on the SR layer. Results: A discriminative pharmacokinetic and IVIVC analysis was applied to all bilayer tablets, offering clearer insights into the plasma concentration and dissolution profiles. Pharmacokinetic studies showed that test formulation F4, which has a 20:20 IR-to-SR ratio, is expected to provide a similar area under the curve (AUC) while prolonging exposure compared to the reference IR tablet. Conclusions: This study highlights the potential of a bilayer tablet approach, combined with discriminative pharmacokinetic and IVIVC analysis, for creating a sustained-release dosage form of ruxolitinib.

Keywords: IVIVC; bilayer tablet; dissolution; ruxolitinib; sustained release formulation.

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Conflict of interest statement

N.K., K.K., S.J., J.K., S.P. and H.C. are current employees of Samyang holdings Corp. This affiliation did not influence the design, execution, or interpretation of the study. Y-J.L. declares that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Manufacturing scheme of ruxolitinib bilayer tablet.
Figure 2
Figure 2
In vitro dissolution profiles of ruxolitinib from different formulations with varying release rates: (A) dissolution profile of Jakavi® in pH 1.2, 4.0, and 6.8 buffers, as well as water; (B) dissolution profile of bilayer tablets using the buffer transition method A (USP).
Figure 3
Figure 3
Plasma concentration time profiles ruxolitinib after oral administration of reference and test formulation; (A) rectangular scale; (B) semi-log scale. The results for the reference formulation, Jakavi®, are the combined results of the control group results from four crossover trials for F1, F2, F3, and F4.
Figure 4
Figure 4
(A) Dose-normalized plasma concentration–time profiles of ruxolitinib, which may have originated from the sustained-release (SR) portion of the bilayer tablet. The dose-normalized plasma concentration of the reference drug is also plotted. The results for the reference drug, Jakavi®, are the combined results of the control group results from four crossover trials for F1, F2, F3, and F4. (B) Release profile of ruxolitinib, potentially from the SR portion of the bilayer tablets.
Figure 5
Figure 5
(A) Mean cumulative fraction absorbed of ruxolitinib from bilayer tablets calculated by using the Loo–Riegelman approach. (B) IVIVC model linear regression plots (y = 0.8883x − 0.0091; correlation coefficient R2 = 0.963) of “Fraction released” vs. “Fraction released” for ruxolitinib bilayer tablets.
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