Inclusion complexes of tricyclic drugs and ß-cyclodextrin: Inherent chirality and dynamic behaviour.
Int J Pharm
; 588: 119775, 2020 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-32805385
ABSTRACT
Amitriptyline (AMT) and cyclobenzaprine (CBZ) are tricyclic drugs used as antidepressant and muscle relaxant, respectively. They show inherently chirality, i.e. they are chiral due to the lack of any symmetry element. As they are used as racemic mixture, diastereomeric inclusion complexes are formed via encapsulation in homochiral ßCD. In this work we show that a suitable combination of NMR methods easily provides details on the chiral recognition, geometry of complexation, rotational dynamics and spatial proximity of selected atom pairs. In particular, we show that 13C NMR can be used to unambiguously assess chiral recognition, demonstrating a higher performance over 1H NMR. The mole fraction of the bound drug and the association constant can be worked out through diffusion experiments, whereas the combination of non-selective, selective and bi-selective relaxation spectra gave insights into the rotational motion of the complexed drug and the spatial proximity of selected proton pairs. The toolkit here proposed provides a thorough characterization of CD/drug inclusion complexes from a physicochemical point of view. This can constructively complement the conventional pharmacological and pharmacokinetic experiments, and can shed light on the understanding of CD/drug formulations.
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Base de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Beta-Ciclodextrinas
Idioma:
En
Revista:
Int J Pharm
Año:
2020
Tipo del documento:
Article