(M1030-08-52) AQbD Method Development for a Venlafaxine Extended-Release Tablets Organic Impurities Procedure

Purpose: Recent changes in the pharmaceutical industry have led to significant paradigm shifts in the pharmaceutical quality environment, moving from compliance-driven to risk-based approaches, and from testing products to building product quality. The goal for this work was to employ an Analytical Quality by Design (AQbD) approach to develop an efficient stability-indicating organic impurities (OI) method for Venlafaxine Extended-Release Tablets.

Methods: Initial risk assessment focused on knowledge gathering for impurities. Twelve impurities were identified from the current USP, EP, BP monographs, other literature, and an exploratory forced degradation study. Multiple rounds of method screening and optimization were performed using Design of Experiments (DoE) and data modeling assisted by the Fusion QbD® software platform.

Results: A new HPLC-UV method with 40 min run time was developed, with selectivity for venlafaxine and 12 impurities. The method is predicted to be robust within the method operable design region (MODR), which was established based on modeling of method optimization data. Analytical control strategies for method performance were proposed, including the experimentally verified MODR and resolution requirements on two critical pairs. The method was validated for the OI procedure with degradant impurities in the range of 0.1 – 1% of the nominal concentration of 0.8 mg/mL of venlafaxine in Venlafaxine Extended-Release Tablets.

Conclusion: An AQbD approach to method development leads to better understanding of critical method parameters and results in more robust methods. The knowledge acquired may allow for flexibility in future modifications of method parameters and aid procedure performance verification along the entire procedure life cycle.

Acknowledgements: We thank S-Matrix Corporation for their support on the use of Fusion QbD® software platform.
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