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NMR search for polymorphic phase transformations in chlorpropamide form-A at high pressures
J Wasicki1, D P Kozlenko, S E Pankov
1Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland. jwasicki@amu.edu.pl
Journal of Pharmaceutical Sciences
|July 16, 2008
Summary
High pressure affects chlorpropamide molecular dynamics, revealing methyl, chlorophenyl ring, and propyl group reorientations. No phase transitions were observed in form-A under these conditions.
Area of Science:
- Solid-state chemistry
- Physical chemistry
- Molecular dynamics
Background:
- Chlorpropamide is an oral hypoglycemic agent.
- Understanding its solid-state behavior under pressure is crucial for pharmaceutical applications.
- High pressure can significantly alter molecular conformations and dynamics.
Purpose of the Study:
- To investigate the effects of high pressure on the molecular dynamics of chlorpropamide form-A.
- To characterize molecular reorientations and their activation parameters.
- To determine if pressure induces phase transformations.
Main Methods:
- Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy was employed.
- Experiments were conducted at pressures up to 800 MPa and temperatures from 90-300 K.
- NMR second moment and spin-lattice relaxation time analyses were performed, complemented by Monte Carlo simulations.
Main Results:
- Detailed molecular dynamics, including methyl group reorientations, chlorophenyl ring oscillations and reorientations, and propyl group reorientations, were identified.
- Activation parameters for these molecular motions were successfully extracted.
- No evidence of phase transformation in chlorpropamide form-A was detected within the studied pressure and temperature ranges.
Conclusions:
- High pressure influences the molecular dynamics of chlorpropamide form-A.
- Specific molecular segments exhibit distinct reorientational behaviors under pressure.
- Chlorpropamide form-A remains stable without phase transitions up to 800 MPa in the investigated temperature range.
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