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Developing a Biorelevant Dissolution Method for an Extrudable Core System (ECS) Osmotic Tablet.
Raymond Chen1, Andrew Blanchard2, Joseph Kushner3
1Analytical Research and Development, Worldwide Research, Development and Medical, Pfizer Inc., Groton, Connecticut, 06340, USA. raymond.chen@pfizer.com.
AAPS Pharmscitech
|December 1, 2021
Summary
A new biorelevant dissolution method was developed for tofacitinib modified-release tablets, enabling successful In Vitro In Vivo Correlation (IVIVC) and quality control.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Biopharmaceutics
Background:
- Developing biorelevant dissolution methods is crucial for predicting in vivo drug performance.
- The tofacitinib 11 mg modified-release tablet utilizes a single-layer extrudable core system (ECS).
- Establishing In Vitro In Vivo Correlation (IVIVC) is essential for regulatory approval and clinical study support.
Purpose of the Study:
- To develop and validate a biorelevant dissolution method for the tofacitinib 11 mg modified-release tablet.
- To support the clinical study by establishing a Level A IVIVC.
- To ensure the method is suitable for quality control.
Main Methods:
- Apparatus 2 (paddles) was chosen over Apparatus 1 (baskets) to minimize variability.
- A 50 mM potassium phosphate buffer at pH 6.8 was selected to mimic small intestinal conditions.
- Designed experiments (DoE) and Japanese basket sinkers were employed to optimize conditions and reduce variability.
Main Results:
- The optimized dissolution method demonstrated reduced variability and eliminated artificial shifts in dissolution profiles.
- The method was validated according to ICH and FDA guidelines, confirming its discriminatory power.
- A Level A IVIVC was successfully established, confirming the method's biorelevance.
Conclusions:
- The developed dissolution method is biorelevant and suitable for quality control of tofacitinib modified-release tablets.
- This method supports the clinical study and regulatory requirements for the tofacitinib ECS tablet.
- The established IVIVC provides a reliable link between in vitro performance and in vivo outcomes.
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