Cyclodextrin's Effect on Permeability and Partition of Nortriptyline Hydrochloride

Cyclodextrin-based delivery systems have been intensively used to improve the bioavailability of drugs through the modification of their pharmaceutically relevant properties, such as solubility, distribution and membrane permeation. The present work aimed to disclose the influence of HP-β-CD and SBE...

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Bibliographic Details
Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2023-07, Vol.16 (7), p.1022
Main Authors: Volkova, Tatyana, Simonova, Olga, Perlovich, German
Format: Article
Language:English
Subjects:
Cellulose
Chemical properties
Cyclodextrins
distribution
Dosage and administration
Drug delivery systems
Drugs
Evaluation
HP-β-CD
Materials
membrane permeability
Membranes
Nortriptyline
nortriptyline hydrochloride
Permeability
PermeaPad barrier
Pharmaceuticals
SBE-β-CD
Vehicles
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Summary:Cyclodextrin-based delivery systems have been intensively used to improve the bioavailability of drugs through the modification of their pharmaceutically relevant properties, such as solubility, distribution and membrane permeation. The present work aimed to disclose the influence of HP-β-CD and SBE-β-CD on the distribution and permeability of nortriptyline hydrochloride (NTT•HCl), a tricyclic antidepressant drug. To this end, the distribution coefficients in the 1-octanol/buffer and n-hexane/buffer model systems and the coefficients of permeability through the cellulose membrane and lipophilic PermeaPad barrier were determined at several cyclodextrin concentrations. The results demonstrated a dramatic decrease in both the distribution and the permeability coefficients as the cyclodextrin concentration rose, with the decrease being more pronounced in SBE-β-CD due to the charge-charge attraction and electrostatic interactions between NTT and SBE-β-CD. It is these interactions that were shown to be responsible for the greater value of the constant of NTT's association with SBE-β-CD than that with HP-β-CD. The findings of this study revealed similar trends in the 1-octanol/buffer 6.8 pH distribution and permeability through the PermeaPad barrier in the presence of CDs. These results were attributed to the determinative role of the distribution coefficient (serving as a descriptor) in permeation through the PermeaPad barrier modeling the lipophilic nature of biological barriers.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph16071022