Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 178, Issue -, Pages 168-178Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2022.08.009
Keywords
Cyclodextrins; Liposomes; Drug diffusion; Molecularly dissolved drug; Mathematical modelling; Numerical data fitting
Categories
Funding
- NordForsk Grant NordicPop (Patient Oriented Product, University Hub project) [85352/D]
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The correlation between in vivo and in vitro data needs further optimization in order to reduce and replace animal testing in pharmaceutical development. This study investigates the mechanisms and kinetics of drug release from nanocarriers by using experimental methods and mathematical modeling. The findings serve as a significant milestone for the development of reliable in vitro/in silico models to predict drug bioavailability when enabling formulations are used.
The correlation between in vivo and in vitro data is yet not sufficiently optimized to allow a significant reduction and replacement of animal testing in pharmaceutical development. One of the main reasons for this lies in the poor mechanistic understanding and interpretation of the physical mechanisms enabling formulation rely on for deploying the drug. One mechanism that still lacks a proper interpretation is the kinetics of drug release from nanocarriers. In this work, we investigate two different types of classical enabling formulations - i) cyclodextrin solutions and ii) liposomal dispersions - by a combination of an experimental method (i.e. UV-Vis localized spectroscopy) and mathematical modelling/numerical data fitting. With this approach, we are able to discriminate precisely between the amount of drug bound to nanocarriers or freely dissolved at any time point; in addition, we can precisely estimate the binding and diffusivity constants of all chemical species (free drug/bound drug). The results obtained should serve as the first milestone for the further development of reliable in vitro/in silico models for the prediction of in vivo drug bioavailability when enabling formulations are used.
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