Development of Biopredictive Dissolution Method for Extended-Release Desvenlafaxine Tablets

This study aimed to develop a biopredictive dissolution method for desvenlafaxine ER tablets using design of experiments (DoE) and physiologically based biopharmaceutics modeling (PBBM) to address the challenge of developing generic drug products by reducing the risk of product failure in pivotal bioequivalence studies. For this purpose, a PBBM was developed in GastroPlus((R)) and combined with a Taguchi L9 design, to evaluate the impact of different drug products (Reference, Generic #1 and Generic #2) and dissolution test conditions on desvenlafaxine release. The influence of the superficial area/volume ratio (SA/V) of the tablets was observed, mainly for Generic #1, which presented higher SA/V than the others, and a high amount of drug dissolved under similar test conditions. The dissolution test conditions of 900 mL of 0.9% NaCl and paddle at 50 rpm with sinker showed to be biopredictive, as it was possible to demonstrate virtual bioequivalence for all products, despite their release-pattern differences, including Generic #3 as an external validation. This approach led to a rational development of a biopredictive dissolution method for desvenlafaxine ER tablets, providing knowledge that may help the process of drug product and dissolution method development.

Automated summary

This study aimed to develop a biopredictive dissolution method for desvenlafaxine ER tablets using design of experiments (DoE) and physiologically based biopharmaceutics modeling (PBBM) to reduce the risk of product failure in bioequivalence studies. A PBBM was developed in GastroPlus(R) and combined with a Taguchi L9 design to evaluate different drug products and dissolution test conditions on desvenlafaxine release. The influence of tablet's superficial area/volume ratio (SA/V) was observed, mainly for Generic #1, which had higher SA/V and showed a higher amount of drug dissolved. The biopredictive dissolution method using 900 mL of 0.9% NaCl and paddle at 50 rpm with sinker demonstrated virtual bioequivalence for all tested products.