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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
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Microphase separation in solid lipid dosage forms as the cause of drug release instability
Diogo Gomes Lopes1, Ioannis Koutsamanis1, Karin Becker2
1Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, Austria.
International Journal of Pharmaceutics
|December 24, 2016
Summary
Preventing microphase separation in lipid formulations is key for stable drug release. This study explains how lipid phase changes during storage cause drug release instability in tripalmitin/polysorbate 65 coatings.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
Background:
- Lipid excipients are gaining interest for taste-masked and modified-release drug formulations.
- Instability and lack of mechanistic understanding hinder the large-scale application of lipid-based drug delivery systems.
Purpose of the Study:
- To investigate the physical stability of a binary tripalmitin/polysorbate 65 lipid coating formulation.
- To understand the mechanisms behind drug release instability in lipid formulations during storage.
Main Methods:
- Differential scanning calorimetry (DSC) for phase diagram construction.
- Polarized light microscopy, scanning electron microscopy (SEM), and X-ray diffraction for microstructure analysis.
- Water uptake, erosion, and N-acetylcysteine drug release studies post-production and after storage.
Main Results:
- Phase growth of polysorbate 65 and tripalmitin was observed during storage, particularly at 40°C.
- Polysorbate 65 leakage from tripalmitin structures led to the formation of impermeable tripalmitin regions.
- Growth of the polysorbate 65 phase resulted in larger, less tortuous hydrophilic channels, impacting drug release.
Conclusions:
- Drug release instability in tripalmitin/polysorbate 65 formulations is attributed to microphase separation during storage.
- Preventing microphase separation is crucial for achieving stable drug release profiles in advanced lipid formulations.
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