Utilizing Quality by Design to Develop and Evaluate Extended-Release Upadacitinib Tablets Incorporating a Biosynthesized Polymer

Abstract

Objectives

The aim of this study was to develop and optimize the production of upadacitinib extended-release tablets containing biosynthesized hydrophilic carriers and/or polymers in the core and coating. This was achieved by applying quality by design (QbD) approach and its built-in quality control aspects to adhere to the general principles of sustainability including subsistence, efficiency, and consistency during the product life cycle. Upadacitinib is an inhibitor of the Janus kinase class of enzymes. In this study, the characterization of the reference product, physicochemical parameters of the drug molecule, and the quality target product profile was considered along with critical attributes of quality to initiate drug development. Critical attributes related to material properties, process parameters, and the formulation variables were identified, and their preliminary level of risk was assessed. The factorial design of an experiment with three center points was achieved using Design Expert v12 to investigate the customary monolithic extended-release tablets of matrix formulation. In order to evaluate tablet performance, critical quality attributes (CQAs) were determined by dissolution tests. Finally, factors that can influence the formulation, including its compositions, manufacturing procedures, and analytical evaluation, were examined. The goal was to identify formulations that exhibit a similar release pattern through the entire 12-h dissolution testing period.

Materials and Methods

Various release rates of biosynthesized polymer-based upadacitinib extended-release formulations were compared to the reference product, Innovator (Rinvoq), using in vitro dissolution test. The selected “T-5” formulation was optimized and evaluated using the QbD method to satisfy the principles of sustainability throughout the product life cycle.

Results

All experimental upadacitinib tablet formulations demonstrated favorable drug release patterns, though not to the required extent. However, the “T-5” formulation released 80% of the drug within the required time.

Conclusions

The “T-5” formulation was considered suitable for the further development of extended-release tablets of upadacitinib, as it contained optimal amount of biosynthesized hydrophilic polymer.