Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC
<b>Objectives</b>: 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-r...
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MDPI AG
2025-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/17/4/432 |
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| author | Namhyuck Kim Kyoungho Kim Seungwei Jeong Jiyeong Kim Helen Cho Young-Joo Lee Sangyeob Park |
| author_facet | Namhyuck Kim Kyoungho Kim Seungwei Jeong Jiyeong Kim Helen Cho Young-Joo Lee Sangyeob Park |
| author_sort | Namhyuck Kim |
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| description | <b>Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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. <b>Conclusions</b>: 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. |
| format | Article |
| id | doaj-art-e5ad111f1b3a44e499d0acf8d87b6bbd |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-e5ad111f1b3a44e499d0acf8d87b6bbd2025-08-20T02:28:28ZengMDPI AGPharmaceutics1999-49232025-03-0117443210.3390/pharmaceutics17040432Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVCNamhyuck Kim0Kyoungho Kim1Seungwei Jeong2Jiyeong Kim3Helen Cho4Young-Joo Lee5Sangyeob Park6Samyang Holdings Corp., 295 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of KoreaSamyang Holdings Corp., 295 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of KoreaSamyang Holdings Corp., 295 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of KoreaSamyang Holdings Corp., 295 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of KoreaSamyang Holdings Corp., 295 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of KoreaDivision of Biopharmaceutics, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 02453, Republic of KoreaSamyang Holdings Corp., 295 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Republic of Korea<b>Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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. <b>Conclusions</b>: 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.https://www.mdpi.com/1999-4923/17/4/432bilayer tabletsustained release formulationruxolitinibIVIVCdissolution |
| spellingShingle | Namhyuck Kim Kyoungho Kim Seungwei Jeong Jiyeong Kim Helen Cho Young-Joo Lee Sangyeob Park Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC Pharmaceutics bilayer tablet sustained release formulation ruxolitinib IVIVC dissolution |
| title | Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC |
| title_full | Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC |
| title_fullStr | Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC |
| title_full_unstemmed | Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC |
| title_short | Development and Evaluation of Bilayer Sustained-Release Tablets of Ruxolitinib Using Discriminative Pharmacokinetic Analysis and IVIVC |
| title_sort | development and evaluation of bilayer sustained release tablets of ruxolitinib using discriminative pharmacokinetic analysis and ivivc |
| topic | bilayer tablet sustained release formulation ruxolitinib IVIVC dissolution |
| url | https://www.mdpi.com/1999-4923/17/4/432 |
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