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Guiding a Diclofenac Sodium Dual-Release Sustained Formulation Development Through In Vitro-In Vivo Relationship
Qizheng Wang1,2, Pengcheng Guo1, Tianci Hu1
1School of Pharmaceutical Sciences, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education & National Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Shanghai 201203, China.
Pharmaceutics
|May 27, 2026
Summary
This study developed a new strategy for generic dual-release drug development using PBPK models and IVIVR. This approach successfully guided formulation screening and demonstrated bioequivalence for a dual-release generic product.
Area of Science:
- Pharmacokinetics
- Drug Development
- Formulation Science
Background:
- Dual-release formulations offer rapid onset and sustained release benefits.
- Conventional methods for dual-release generic development are risky and inefficient.
- Predictive modeling can optimize generic formulation screening.
Purpose of the Study:
- To establish a quality-related media condition for dual-release generic formulation screening.
- To guide generic formulation development using PBPK models and IVIVR.
- To evaluate the bioequivalence of a dual-release generic product.
Main Methods:
- Constructed PBPK models and IVIVR for a reference dual-release product (Difene®).
- Identified optimal IVIVR conditions in pH 4.0-6.0-6.8 media.
- Screened generic formulations using the established quality-related media.
- Conducted pharmacokinetic studies in beagle dogs to assess bioequivalence.
Main Results:
- Successfully established PBPK models and IVIVR with optimal performance.
- Achieved an f2 factor of 76 for the optimized generic product in vitro.
- Demonstrated bioequivalence between the generic and reference products in beagle dogs (AUC, Cmax within 80-125%).
Conclusions:
- The study presents a strategic approach for generic dual-release formulation development.
- Established PBPK models and IVIVR provide a novel framework for optimizing generic drug screening.
- This method enhances the success rate of bioequivalence studies for complex dosage forms.
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