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Development of a Universal In Vivo Predictive Dissolution Method for a Borderline BCS III/IV Drug Guided by Modeling
Mauricio A García1, Fernando Tapia1, Benjamín Escares1,2
1Departamento de Farmacia, Escuela de Química y Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Campus San Joaquín, Macul, Santiago 7820436, Chile.
Molecular Pharmaceutics
|September 22, 2025
Summary
A new in vivo predictive dissolution (IPD) method using a mini-vessel apparatus was developed for acyclovir tablets. This method accurately predicts drug plasma concentrations, ensuring bioequivalence for all strengths.
Area of Science:
- Pharmacokinetics and Drug Delivery
- Pharmaceutical Sciences
Background:
- Establishing in vivo predictive dissolution (IPD) requires biopredictive dissolution conditions.
- Acyclovir's higher dose strengths (800 mg) exceed solubility thresholds and lack sink conditions due to poor permeability.
Purpose of the Study:
- To develop a universal IPD method for acyclovir immediate-release tablets.
- To optimize dissolution conditions using computational simulations and experimental data.
Main Methods:
- Utilized a mini-vessel/mini-paddle apparatus for dissolution testing.
- Employed physiologically based pharmacokinetic (PBPK) modeling with computational simulations.
- Explored various apparatus volumes and stirring conditions, validating with in-human and virtual bioequivalence studies.
Main Results:
- Dissolution in 900 mL medium overpredicted plasma profiles for the 800 mg acyclovir strength.
- Optimized conditions (135 mL HCl, pH 2.0, 150 rpm) accurately predicted plasma profiles for all strengths.
- Validated predictive potential through in-human and virtual bioequivalence studies.
Conclusions:
- The developed mini-vessel dissolution method serves as a universal IPD for acyclovir immediate-release tablets.
- This method ensures accurate prediction of drug performance across different dosage strengths.
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