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Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid
Gulenay Guner1, Ayesha Amjad1, Matthew Berrios1
1Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Pharmaceutics
|February 25, 2023
Summary
Residual drug nanocrystals significantly impact amorphous solid dispersion (ASD) performance. This study highlights using drug nanoparticles in dissolution and desupersaturation tests for more accurate ASD development.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Physical Chemistry
Background:
- Amorphous solid dispersions (ASDs) enhance drug solubility but are prone to crystallization.
- Residual drug crystals in ASDs can negatively affect drug release and stability.
- Understanding crystallization kinetics is crucial for developing stable and effective ASD formulations.
Purpose of the Study:
- To investigate the impact of residual drug crystal size on precipitation in griseofulvin ASDs.
- To compare the effects of nanoparticle seeds versus micron-sized seeds in desupersaturation and dissolution tests.
- To evaluate the precipitation inhibition capabilities of different polymers in griseofulvin ASDs.
Main Methods:
- Preparation of griseofulvin ASDs using spray-drying with polymers: Soluplus (Sol), Kollidon VA64 (VA64), and hydroxypropyl methyl cellulose (HPMC).
- Generation of nanoparticle seeds via wet media milling.
- Conducting solvent-shift (desupersaturation) and dissolution tests with varying seed sizes and loadings.
- Characterization using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), X-ray Powder Diffraction (XRPD), and Differential Scanning Calorimetry (DSC).
Main Results:
- Drug nanoseeds induced faster and more extensive desupersaturation compared to micron-sized crystals.
- Increased seed loading enhanced desupersaturation.
- Soluplus (Sol) demonstrated the highest nucleation inhibition capability, followed by HPMC and VA64.
- Only Sol-based ASDs achieved significant supersaturation in dissolution tests, which decreased with higher nanoseed loading.
Conclusions:
- Drug nanocrystals are more realistic surrogates than micron-sized crystals for studying residual crystal impacts in ASDs.
- The size and loading of residual crystals significantly influence desupersaturation and dissolution behavior.
- This study underscores the importance of employing drug nanocrystals in ASD development for accurate performance evaluation.
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