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In Vitro-In Silico Approach in the Development of Clopidogrel Solid Dispersion Formulations
Ehlimana Osmanović Omerdić1,2, Sandra Cvijić1, Jelisaveta Ignjatović1,3
1Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
Bioengineering (Basel, Switzerland)
|April 26, 2025
Summary
This study optimized clopidogrel solid dispersions (SDs) using an in vitro-in silico approach. Specific polymer formulations significantly enhanced clopidogrel bioavailability and improved pharmacokinetic profiles.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Pharmacokinetics
Background:
- Clopidogrel's bioavailability can be limited by its pharmacokinetic profile.
- Solid dispersion (SD) technology offers a strategy to enhance drug absorption.
- Optimizing SD formulation factors is crucial for improving drug efficacy.
Purpose of the Study:
- To investigate the impact of solid dispersion formulation factors on clopidogrel bioavailability and pharmacokinetics.
- To develop and validate a physiologically based biopharmaceutical model (PBBM) for clopidogrel.
- To predict the pharmacokinetic performance of clopidogrel SDs using an in vitro-in silico approach.
Main Methods:
- Preparation of clopidogrel solid dispersions using poloxamer 407 and copovidone at drug-to-polymer ratios of 1:5 and 1:9.
- In vitro dissolution testing under varying pH conditions.
- Development and validation of a clopidogrel-specific physiologically based biopharmaceutical model (PBBM).
- In silico prediction of pharmacokinetic profiles using in vitro dissolution data as input for the PBBM.
Main Results:
- Polymer type and ratio significantly influenced clopidogrel release from SDs; higher polymer content decreased release.
- SDs with copovidone (1:5) and poloxamer (1:9) demonstrated potential for over 100% improvement in drug absorption and bioavailability compared to immediate-release tablets.
- The poloxamer (1:9) formulation may reduce pharmacokinetic variability by promoting absorption in the distal intestine, potentially lowering first-pass metabolism.
Conclusions:
- An in vitro-in silico approach is effective for developing and optimizing clopidogrel solid dispersion formulations.
- Specific SD formulations, particularly with copovidone (1:5) and poloxamer (1:9), can significantly enhance clopidogrel bioavailability.
- Targeting distal intestinal absorption may be a viable strategy to improve clopidogrel's pharmacokinetic profile and reduce variability.
Keywords:
clopidogrelcopovidonein silico physiologically based biopharmaceutics modelingin vitro dissolution testpoloxamer 407solid dispersionsMore Related Videos
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