Development and validation of a Level A in-vitro in-vivo correlation for tofacitinib modified-release tablets using extrudable core system osmotic delivery technology
| Autor: | Christine Alvey, Manisha Lamba, Thomas C. Stock, Mary Anne Nemeth, Andrew Blanchard, Joseph Kushner, Vincent DeMatteo, Ronnie Wang, Raymond Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Osmosis Technology Pharmaceutical Science Administration Oral Biological Availability In Vitro Techniques Correlation Arthritis Rheumatoid Random Allocation IVIVC Drug Delivery Systems Pharmacokinetics Piperidines In vivo Humans Janus Kinase Inhibitors In vitro in vivo Tofacitinib Dose-Response Relationship Drug Chemistry In vivo absorption Middle Aged Healthy Volunteers Drug Liberation Pyrimidines Solubility Core system Biomedical engineering Tablets |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 147 |
| ISSN: | 1879-0720 |
| Popis: | Purpose To determine if a validated Level A in-vitro in-vivo correlation (IVIVC) could be achieved with the extrudable core system (ECS) osmotic tablet platform. Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis. Methods Fast-, medium-, and slow-release modified-release formulations of 11 mg tofacitinib ECS tablets, and one formulation of 22 mg tofacitinib ECS tablet, were manufactured. In vitro dissolution of the tofacitinib ECS tablets was performed using USP Apparatus 2 (paddles) and in vivo pharmacokinetic (PK) data were obtained from a Phase 1 study in healthy volunteers. A 5 mg immediate-release formulation tablet was included to support deconvolution of the tofacitinib ECS PK tablet data to obtain the in vivo absorption profiles. A linear, piecewise correlation and a simple linear correlation were used to build and validate two IVIVC models. Results The prediction errors (PEs) for the linear, piecewise correlation met the Food and Drug Administration's criteria for establishing a Level A IVIVC, with a maximum absolute individual internal PE of 4.6%, a maximum absolute average internal PE of 3.9%, and a maximum absolute external PE of 8.4% obtained. Conclusions This study demonstrates that the tofacitinib ECS osmotic tablet platform can achieve a Level A IVIVC, similar to other osmotic delivery systems. |
| Databáze: | OpenAIRE |
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