Surface-enhanced crystallization of amorphous nifedipine
Lei Zhu1, Letitia Wong, Lian Yu
1School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA.
Molecular Pharmaceutics
|May 13, 2009
Summary
Amorphous nifedipine (NIF) crystallizes faster at its surface than in the bulk. An ultrathin gold coating effectively inhibits this surface-enhanced crystallization, maintaining drug solubility.
Area of Science:
- Materials Science
- Physical Chemistry
- Pharmaceutical Science
Background:
- Amorphous solids offer enhanced solubility and dissolution rates, crucial for poorly soluble drug delivery.
- Crystallization of amorphous drugs negates these advantages, necessitating stabilization strategies.
- Previous studies identified surface-enhanced crystallization in amorphous indomethacin.
Purpose of the Study:
- To investigate surface-enhanced crystallization in a second amorphous system, amorphous nifedipine (NIF).
- To determine the effect of an ultrathin coating on surface crystallization kinetics.
- To elucidate the role of molecular mobility in surface crystallization below the glass transition temperature.
Main Methods:
- Comparative analysis of crystal growth rates at the free surface versus the bulk of amorphous nifedipine.
- Investigation of the effect of a 10 nm gold coating on surface crystallization.
- Temperature-dependent studies of crystallization kinetics relative to the glass transition temperature (Tg).
Main Results:
- Crystal growth at the amorphous NIF surface was over an order of magnitude faster than in the bulk below Tg (42°C).
- A thin gold coating reduced surface crystallization rates to bulk levels.
- Surface-enhanced crystallization was more significant near and below Tg, indicating its importance in the glassy state.
Conclusions:
- A mobile surface layer of molecules contributes to significantly faster crystallization compared to the bulk.
- Ultrathin coatings can effectively suppress surface-enhanced crystallization, preserving the amorphous state.
- Findings support the hypothesis of enhanced molecular mobility at the surface of amorphous solids.
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