Development of Biopredictive Dissolution Method for Extended-Release Desvenlafaxine Tablets

Abstract

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® 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.

A Rational Approach to Predicting Immediate Release Formulation Behavior in Multiple Gastric Motility Patterns: A Combination of a Biorelevant Apparatus, Design of Experiments, and Machine Learning

“…A successful case of the utilization of the DoE method to optimize biopredictive dissolution conditions and to build in vitro–in vivo correlations for an IR capsule was presented by Mercuri et al [ 46 ]. Moreover, Carapeto et al utilized DoE and physiologically based biopharmaceutics modeling to develop a biopredictive dissolution method [ 47 ]. However, these approaches applied multiple linear regression and analysis of variance to assess how the composition and volume of the dissolution media, apparatus type, dosage form, and rotational speed influenced the in vitro drug dissolution.…”

Model-Informed Drug Development: In Silico Assessment of Drug Bioperformance following Oral and Percutaneous Administration

“…On the other hand, PBBM can be used to simulate drug dissolution and estimate the influence of drug-, formulation-, or physiology-related factors on this process to clinically relevant dissolution specifications. The link between bio-predictive or bio-relevant dissolution testing and PBBM and the utility of PBBM in terms of identifying in vivo relevant dissolution testing conditions or issues related to drug dissolution have been addressed in a number of publications [ 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ].…”