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Development of an In Vitro-In Vivo Correlation for Sitagliptin and Metformin Prolonged-release Tablet Formulations
Rajkumar Boddu1, Harikiran Chary Vadla1, Vamshi Ramana Prathap1
1Product Development, AET Laboratories Pvt. Ltd, Sangareddy District, Telangana State, India
Turkish Journal of Pharmaceutical Sciences
|April 27, 2021
Summary
This study established a validated in vitro-in vivo correlation (IVIVC) for a fixed-dose combination (FDC) of sitagliptin and metformin. The validated IVIVC model can predict drug performance and supports the FDC
Area of Science:
- Pharmacokinetics and Drug Development
- Pharmaceutical Sciences
- Clinical Pharmacology
Background:
- Fixed-dose combinations (FDCs) require robust methods for quality control and lifecycle management.
- Establishing an in vitro-in vivo correlation (IVIVC) is crucial for predicting drug product performance.
- Bioequivalence studies provide essential data for developing and validating IVIVC models.
Purpose of the Study:
- To establish and validate an in vitro-in vivo correlation (IVIVC) for a fixed-dose combination (FDC) of sitagliptin and metformin.
- To assess the safety and tolerability of the FDC compared to reference formulations.
- To determine if the developed IVIVC model meets regulatory criteria for prediction.
Main Methods:
- A bioequivalence study was conducted using an FDC (sitagliptin 100 mg/metformin 1000 mg prolonged release) and reference products (Januvia® 100 mg + Glucophage® SR 1000 mg).
- Plasma concentration-time data and dissolution profiles were used to establish a Level A IVIVC.
- Pharmacokinetic modeling, Levy plots, and prediction error analysis were employed to validate the correlation.
Main Results:
- The FDC exhibited high dissolution rates for both sitagliptin (91%-95% fasted, 89%-91% fed) and metformin (96%-98% fasted, 89%-95% fed).
- Levy plots showed strong linear correlations (regression coefficients > 0.900) between in vitro release and in vivo parameters.
- The IVIVC model demonstrated high internal and external predictabilities (prediction error < 10%), meeting FDA criteria.
Conclusions:
- A validated Level A IVIVC was successfully established for the sitagliptin/metformin FDC.
- The validated IVIVC model can be utilized for product lifecycle management and as a surrogate for in vivo studies.
- The FDC demonstrated favorable safety and tolerability, with fewer adverse events compared to reference products, indicating its suitability for human use.
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