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Simulation of the release from a multiparticulate system validated by single pellet and dose release experiments
Per Borgquist1, Pernilla Nevsten, Bernt Nilsson
1Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
Summary
A simplified model accurately predicts drug release from multiple-pellet systems by analyzing individual pellet variations. This enhanced model aids in optimizing pharmaceutical formulations for controlled drug delivery.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Mathematical Modeling
Background:
- Controlled-release formulations often utilize multiple pellets to achieve desired drug release profiles.
- Understanding and predicting drug release from these complex systems is crucial for formulation development and optimization.
- Existing single-pellet models may not adequately capture the variability observed in multi-pellet systems.
Purpose of the Study:
- To simplify and adapt a single-pellet drug release model for predicting release from multiple-pellet pharmaceutical systems.
- To estimate key release-controlling parameters (pellet core radius, mass transfer coefficient, lag time) from experimental data.
- To validate the predictive capability of the developed model for dose-level release profiles.
Main Methods:
- Modification and simplification of a previously described single-pellet release model.
- Estimation of release-controlling parameters using single-pellet release data.
- Inputting parameter distributions from single pellets into a multiple-pellet model.
- Validation of model predictions against experimentally measured dose-level release profiles.
Main Results:
- The simplified single-pellet model accurately estimated pellet core radius and lag time.
- Individual pellet release profiles exhibited significant variability, not apparent at the dose level.
- The multiple-pellet model, using parameter distributions, successfully predicted dose-level release profiles consistent with experimental data.
- Simulations showed that smaller pellet subunits (at constant total dose) increase release rate and reduce variability.
Conclusions:
- The developed multiple-pellet release model effectively predicts dose-level drug release profiles.
- The model accounts for inherent variability in individual pellet performance, crucial for accurate predictions.
- This predictive modeling approach offers significant value in optimizing existing controlled-release formulations and developing new ones.