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Stability characterization, kinetics and mechanism of tacrolimus degradation in cyclodextrin solutions

Stability characterization, kinetics and mechanism of tacrolimus degradation in cyclodextrin solutions


Title: Stability characterization, kinetics and mechanism of tacrolimus degradation in cyclodextrin solutions
Author: Prajapati, Manisha
Eiríksson, Finnur Freyr
Loftsson, Thorsteinn   orcid.org/0000-0002-9439-1553
Date: 2020
Language: English
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Lyfjafræðideild (HÍ)
Faculty of Pharmaceutical Sciences (UI)
Series: International Journal of Pharmaceutics;Volume 586, 2020, 119579
ISSN: 0378-5173
DOI: 10.1016/j.ijpharm.2020.119579
Subject: Cyclodextrins; Tacrolimus; Stability; Solubility; Kinetics; Sýklódextrín; Lyfjaefnafræði
URI: https://hdl.handle.net/20.500.11815/2458

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Citation:

Prajapati, M., Eiriksson, F. F., & Loftsson, T. (2020). Stability characterization, kinetics and mechanism of tacrolimus degradation in cyclodextrin solutions. International Journal of Pharmaceutics, 586, 119579. doi:https://doi.org/10.1016/j.ijpharm.2020.119579

Abstract:

Tacrolimus is a macrolide lactone and potent immunosuppressant. It is highly lipophilic and has very limited aqueous solubility. Tacrolimus is highly susceptible to hydrolysis which results in very limited stability in aqueous solutions. Besides this, tacrolimus also undergoes dehydration and epimerization. Cyclodextrin (CD) complexation can increase the solubility and stability of hydrophobic drugs in aqueous solutions through the formation of drug/CD complexes. The aim of this study was to investigate degradation kinetics, mechanism and stability of tacrolimus in aqueous CD solutions, with the ultimate goal of developing an aqueous vehicle for ophthalmic delivery. For this, phase-solubility and kinetic studies in aqueous solutions containing different CDs at different pH values were performed. Mass spectrometry studies were also performed to elucidate the degradation mechanism of the drug in aqueous CD solution. The study showed that the drug has maximum stability between pH 4 and 6 and hydrolysis was the main cause of tacrolimus degradation in aqueous 2-hydroxypropyl-βCD (HPβCD) solutions. βCD and its derivatives were the better CD solubilizers for tacrolimus. The solubility and stability studies were further conducted with CD and surfactants, which is tyloxapol, tween 80 and poloxamer 407, where the combination provided better results compared to individual components.

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