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Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions.
D J van Drooge1, W L J Hinrichs, H W Frijlink
1Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute of Drug Exploration (GUIDE), Antonius Deusinglaan 1, 9713AV, Groningen, The Netherlands.
Summary
Investigating anomalous dissolution of amorphous solid dispersions revealed that fast drug release occurs when drug and sugar carrier dissolution profiles coincide. This is achieved with low drug loads or slow-dissolving carriers like inulin.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
Background:
- Amorphous solid dispersions are crucial for improving the solubility and bioavailability of poorly soluble drugs.
- Understanding the dissolution mechanisms of these dispersions is key to optimizing drug delivery.
Purpose of the Study:
- To investigate the anomalous dissolution behavior of tablets containing amorphous sugar glass dispersions of diazepam.
- To elucidate the mechanisms governing drug release based on carrier dissolution rate and drug load.
Main Methods:
- Prepared amorphous solid dispersions of diazepam in various sugar glasses (sucrose, trehalose, inulinDP11, inulinDP23) using freeze-drying.
- Investigated drug and carrier dissolution profiles under varying drug loads and carrier properties.
- Analyzed dissolution mechanisms, including crystallization and release kinetics.
Main Results:
- Fast diazepam release (80% in 20 min) observed when drug and sugar dissolution profiles coincided, typically with slow-dissolving carriers (inulins) or low drug loads.
- Non-coinciding profiles (fast-dissolving carriers, high drug loads) resulted in slower diazepam release, characterized by three phases: acceleration with crystallization, steady-state zero-order release, and slow dissolution of crystallized drug.
- A model was proposed to explain the observed anomalous dissolution phenomena.
Conclusions:
- Dissolution behavior of amorphous solid dispersions is highly dependent on the interplay between carrier dissolution rate and drug load.
- Coinciding dissolution profiles are essential for rapid drug release, while non-coinciding profiles lead to complex, multi-phasic release kinetics.
- The proposed model provides a framework for understanding and predicting dissolution behavior in amorphous solid dispersion tablets.