These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Molecular mobility study of amorphous and crystalline phases of a pharmaceutical product by thermally stimulated current spectrometry.
    Author: Boutonnet-Fagegaltier N, Menegotto J, Lamure A, Duplaa H, Caron A, Lacabanne C, Bauer M.
    Journal: J Pharm Sci; 2002 Jun; 91(6):1548-60. PubMed ID: 12115853.
    Abstract:
    Two crystalline forms and the amorphous state of irbesartan, a pharmaceutical drug chosen as a model, were analyzed by Thermally Stimulated Current (TSC) spectroscopy, a powerful technique currently used in polymer science to investigate the molecular dynamics of heterogeneous and complex materials. Whereas no specific dielectric response was noted for the B crystalline form, the A form of irbesartan exhibited molecular motions localized inside its channel structure. The dynamics involved in the dielectric glass transition of amorphous samples followed a compensation law characteristic of highly cooperative relaxation processes. Concerning the amorphous content in physical mixtures, a calibration curve and a limit of detection (2.5%) were established. The limit of detection could be improved by optimizing the TSC experimental parameters. The amorphous sample recrystallized at a single temperature was interpreted by the "idealized one-state model" defined here to describe systems composed of identical semicrystalline particles in which amorphous and crystalline phases are independent of each other (i.e., no chemical and physical interaction between the two phases). Therefore, the idealized one-state model may be simulated by a two-state model, which is representative of the two-phase model. Other samples recrystallized through a complex annealing stage were explained by the classical one-state model in agreement with the three-phase model used to describe bulk semicrystalline systems. These results demonstrate that, as for polymers, the semicrystalline state of pharmaceutical drugs should not be considered as a single state but as a more complex system that can be described as an idealized one-state model or a one-state model depending on the applied thermal treatment. These results give a new view that should be taken into account in the development of amorphous pharmaceutical drugs and formulations.
    [Abstract] [Full Text] [Related] [New Search]