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Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability

The pharmacologically relevant physicochemical properties of the antiandrogen drug bicalutamide (BCL) have been determined for the first time. Solubility in aqueous solution, 1-octanol, n-hexane, and ethanol was measured by the shake flask method in the temperature range of 293.15–313.15 K. The comp...

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Autores principales: Volkova, Tatyana V., Simonova, Olga R., Perlovich, German L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954523/
https://www.ncbi.nlm.nih.gov/pubmed/35336047
http://dx.doi.org/10.3390/pharmaceutics14030674
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author Volkova, Tatyana V.
Simonova, Olga R.
Perlovich, German L.
author_facet Volkova, Tatyana V.
Simonova, Olga R.
Perlovich, German L.
author_sort Volkova, Tatyana V.
collection PubMed
description The pharmacologically relevant physicochemical properties of the antiandrogen drug bicalutamide (BCL) have been determined for the first time. Solubility in aqueous solution, 1-octanol, n-hexane, and ethanol was measured by the shake flask method in the temperature range of 293.15–313.15 K. The compound was shown to be poorly soluble in aqueous medium and n-hexane; at the same time, an essentially higher solubility in the alcohols was revealed. The following order of molar solubility was determined: ethanol > 1-octanol > water ≈ n-hexane. The solubility was correlated with the Van’t Hoff and Apelblat equations. Evaluation of the Hansen solubility parameters and the atomic group contribution approach of Hoftyzer and Van Krevelen demonstrated consistency with the experimental data and good potential adsorption of bicalutamide. The temperature dependences of the distribution coefficients in the 1-octanol/water and n-hexane/water two-phase systems were measured and discussed in the framework of the thermodynamic approach. The ∆logD parameter determined from the distribution experiment clearly demonstrated the preference of the lipophilic delivery pathways for the compound in the biological media. The overall thermodynamic analysis based on the solubility and distribution results of the present study and the sublimation characteristics published previously has been performed. To this end, the thermodynamic parameters of the dissolution, solvation, and transfer processes were calculated and discussed in view of the solute-solvent interactions. The permeation rate of BCL through the PermeaPad barrier was measured and compared with PAMPA permeability.
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spelling pubmed-89545232022-03-26 Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability Volkova, Tatyana V. Simonova, Olga R. Perlovich, German L. Pharmaceutics Article The pharmacologically relevant physicochemical properties of the antiandrogen drug bicalutamide (BCL) have been determined for the first time. Solubility in aqueous solution, 1-octanol, n-hexane, and ethanol was measured by the shake flask method in the temperature range of 293.15–313.15 K. The compound was shown to be poorly soluble in aqueous medium and n-hexane; at the same time, an essentially higher solubility in the alcohols was revealed. The following order of molar solubility was determined: ethanol > 1-octanol > water ≈ n-hexane. The solubility was correlated with the Van’t Hoff and Apelblat equations. Evaluation of the Hansen solubility parameters and the atomic group contribution approach of Hoftyzer and Van Krevelen demonstrated consistency with the experimental data and good potential adsorption of bicalutamide. The temperature dependences of the distribution coefficients in the 1-octanol/water and n-hexane/water two-phase systems were measured and discussed in the framework of the thermodynamic approach. The ∆logD parameter determined from the distribution experiment clearly demonstrated the preference of the lipophilic delivery pathways for the compound in the biological media. The overall thermodynamic analysis based on the solubility and distribution results of the present study and the sublimation characteristics published previously has been performed. To this end, the thermodynamic parameters of the dissolution, solvation, and transfer processes were calculated and discussed in view of the solute-solvent interactions. The permeation rate of BCL through the PermeaPad barrier was measured and compared with PAMPA permeability. MDPI 2022-03-18 /pmc/articles/PMC8954523/ /pubmed/35336047 http://dx.doi.org/10.3390/pharmaceutics14030674 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Volkova, Tatyana V.
Simonova, Olga R.
Perlovich, German L.
Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability
title Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability
title_full Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability
title_fullStr Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability
title_full_unstemmed Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability
title_short Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability
title_sort physicochemical profile of antiandrogen drug bicalutamide: solubility, distribution, permeability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954523/
https://www.ncbi.nlm.nih.gov/pubmed/35336047
http://dx.doi.org/10.3390/pharmaceutics14030674
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