Looking behind the Solubilization Curtain: Microdialysis Provides Near-Real-Time Noncolloidal Drug Concentrations
Mikkel Højmark Tønning1, Annette Bauer-Brandl1, Martin Brandl1
1Department of Physics, Chemistry & Pharmacy, University of Southern Denmark, 5230 Odense, Denmark.
Molecular Pharmaceutics
|October 3, 2025
Summary
Microdialysis offers a more accurate way to test lipid-based formulations by separating dissolved drugs from micelles during in vitro lipolysis. This method improves understanding of drug absorption compared to traditional centrifugation techniques.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Biopharmaceutics
Background:
- Lipid-based formulations improve oral absorption of poorly water-soluble drugs.
- Traditional in vitro lipolysis using centrifugation may misjudge formulation performance by not separating truly dissolved drug from colloidal assemblies.
- This can lead to in vitro-in vivo mismatches in predicting drug absorption.
Purpose of the Study:
- To evaluate microdialysis as an alternative sampling technique for in vitro lipolysis.
- To differentiate truly dissolved drug molecules (free fraction) from colloid-associated molecules.
- To achieve a better mechanistic understanding of lipid-based formulation performance.
Main Methods:
- Tested microdialysis compatibility with standard lipolysis medium components (bile salts, phospholipids, enzymes).
- Used indomethacin and a medium-chain type IIIB lipid formulation as models.
- Compared microdialysis sampling with conventional centrifugation-based sampling during in vitro lipolysis.
Main Results:
- Microdialysis is compatible with lipolysis conditions and provides near-real-time free drug concentrations.
- Microdialysis revealed indomethacin supersaturation, independent of lipolysis, and indicated digestion did not affect formulation performance.
- Conventional sampling suggested lipolysis decreased solubilization capacity, contradicting microdialysis findings and literature examples.
Conclusions:
- Microdialysis accurately measures the free drug fraction, overcoming limitations of centrifugation in in vitro lipolysis.
- This technique offers a more mechanistically sound evaluation of lipid-based formulation performance.
- Microdialysis is a promising complementary tool for assessing lipid-based formulations in vitro.
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