DoE- and PBBM-Driven Formulation Development of an Extended-Release Donepezil Tablet

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Computational Pharmaceutics

Background:

• Extended-release (XR) formulation development is complex and resource-intensive.
• Optimizing formulation variables to achieve desired drug release profiles is challenging.
• Current methods often require extensive in vivo studies, increasing development time and cost.

Purpose of the Study:

• To integrate Design of Experiments (DoE) with Physiologically Based Biopharmaceutics Modeling (PBBM) for efficient XR formulation development.
• To optimize an extended-release donepezil (DPZ) formulation using a systematic experimental design.
• To assess the potential for virtual bioequivalence (VBE) studies.

Main Methods:

• A Box-Behnken experimental design was employed to evaluate the impact of HPMC 100, HPMC 4000, and NaCMC on drug release, hydration, and erosion.
• In vitro dissolution data were integrated into a PBBM framework.
• Physiologically Based Biopharmaceutics Modeling (PBBM) was used to simulate drug release and pharmacokinetics.

Main Results:

• An optimized XR formulation for donepezil (DPZ) was developed with a dissolution profile comparable to the reference product.
• The integrated DoE and PBBM approach provided robust predictive insights into formulation performance.
• Virtual bioequivalence (VBE) assessments were enabled, reducing reliance on in vivo studies.

Conclusions:

• The combined DoE and PBBM methodology offers a scalable and generalizable strategy for efficient XR formulation development.
• Leveraging advanced statistical methods and in silico modeling accelerates the development of cost-effective, bioequivalent drug products.
• This integrated approach significantly reduces time-to-market for pharmaceutical innovations.