Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam

Background: The bioavailability of a drug depends, among other parameters,on solubility. One of the strategies used to enhance the solubility of sparingly solubledrugs is the use of excipients. Excipients can interact with the drug by increasing its solubilityand/or stabilizing supersaturated soluti...

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Autores: Lucero Borja, Diego Sebastián, Ruiz, Rebeca, Fuguet i Jordà, Elisabet, Ràfols Llach, Clara
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/221312
Acceso en línea:https://hdl.handle.net/2445/221312
Access Level:acceso abierto
Palabra clave:Excipients
Solubilitat
Polímers
Solubility
Polymers
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spelling Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and PiroxicamLucero Borja, Diego SebastiánRuiz, RebecaFuguet i Jordà, ElisabetRàfols Llach, ClaraExcipientsSolubilitatPolímersExcipientsSolubilityPolymersBackground: The bioavailability of a drug depends, among other parameters,on solubility. One of the strategies used to enhance the solubility of sparingly solubledrugs is the use of excipients. Excipients can interact with the drug by increasing its solubilityand/or stabilizing supersaturated solutions. Some of the most common excipientsare cyclodextrins and hydrophilic polymers. Objectives: The effect of two cyclodextrins(captisol and cavasol) and three hydrophilic polymers (klucel, kollidon and plasdoneS630) on the solubility of three ionizable drugs (benzthiazide, isoxicam, and piroxicam) isevaluated at biorelevant pH values, using two complementary techniques. Methods: Thesolubility enhancement was evaluated by the comparison of the solubility with and withoutthe presence of excipients through the shake-flask and CheqSol methodology. Results:Captisol and cavasol slightly increase the concentration of the neutral species of the drugsin the solution before precipitation begins, although they do not enhance the supersaturationduration nor the thermodynamic solubility of the drugs. The increase in solubilityin the presence of cyclodextrins is mainly caused by the ionization state of the drug. Hydrophilicpolymers not only improve thermodynamic solubility but also the extent andthe duration of the supersaturation. Some metastable forms are observed for benzthiazideand isoxicam in the presence of kollidon and plasdone S630. Conclusions: The shake-flaskmethod enabled the evaluation of thermodynamic solubility both in the absence and presenceof excipients. Meanwhile, the CheqSol method provided insights into the presenceof supersaturated solutions. Different behavior is observed depending on the nature ofthe excipient.MDPI2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/221312Articles publicats en revistes (Enginyeria Química i Química Analítica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/https://doi.org/10.3390/pharmaceutics17050571Pharmaceutics, 2025, vol. 17https://doi.org/https://doi.org/10.3390/pharmaceutics17050571cc-by (c) Lucero-Borja, D. et al., 2025http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2213122026-05-27T06:46:51Z
dc.title.none.fl_str_mv Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam
title Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam
spellingShingle Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam
Lucero Borja, Diego Sebastián
Excipients
Solubilitat
Polímers
Excipients
Solubility
Polymers
title_short Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam
title_full Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam
title_fullStr Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam
title_full_unstemmed Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam
title_sort Influence of Ionization and the Addition of Cyclodextrins andHydrophilic Excipients on the Solubility of Benzthiazide,Isoxicam, and Piroxicam
dc.creator.none.fl_str_mv Lucero Borja, Diego Sebastián
Ruiz, Rebeca
Fuguet i Jordà, Elisabet
Ràfols Llach, Clara
author Lucero Borja, Diego Sebastián
author_facet Lucero Borja, Diego Sebastián
Ruiz, Rebeca
Fuguet i Jordà, Elisabet
Ràfols Llach, Clara
author_role author
author2 Ruiz, Rebeca
Fuguet i Jordà, Elisabet
Ràfols Llach, Clara
author2_role author
author
author
dc.subject.none.fl_str_mv Excipients
Solubilitat
Polímers
Excipients
Solubility
Polymers
topic Excipients
Solubilitat
Polímers
Excipients
Solubility
Polymers
description Background: The bioavailability of a drug depends, among other parameters,on solubility. One of the strategies used to enhance the solubility of sparingly solubledrugs is the use of excipients. Excipients can interact with the drug by increasing its solubilityand/or stabilizing supersaturated solutions. Some of the most common excipientsare cyclodextrins and hydrophilic polymers. Objectives: The effect of two cyclodextrins(captisol and cavasol) and three hydrophilic polymers (klucel, kollidon and plasdoneS630) on the solubility of three ionizable drugs (benzthiazide, isoxicam, and piroxicam) isevaluated at biorelevant pH values, using two complementary techniques. Methods: Thesolubility enhancement was evaluated by the comparison of the solubility with and withoutthe presence of excipients through the shake-flask and CheqSol methodology. Results:Captisol and cavasol slightly increase the concentration of the neutral species of the drugsin the solution before precipitation begins, although they do not enhance the supersaturationduration nor the thermodynamic solubility of the drugs. The increase in solubilityin the presence of cyclodextrins is mainly caused by the ionization state of the drug. Hydrophilicpolymers not only improve thermodynamic solubility but also the extent andthe duration of the supersaturation. Some metastable forms are observed for benzthiazideand isoxicam in the presence of kollidon and plasdone S630. Conclusions: The shake-flaskmethod enabled the evaluation of thermodynamic solubility both in the absence and presenceof excipients. Meanwhile, the CheqSol method provided insights into the presenceof supersaturated solutions. Different behavior is observed depending on the nature ofthe excipient.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/221312
url https://hdl.handle.net/2445/221312
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/https://doi.org/10.3390/pharmaceutics17050571
Pharmaceutics, 2025, vol. 17
https://doi.org/https://doi.org/10.3390/pharmaceutics17050571
dc.rights.none.fl_str_mv cc-by (c) Lucero-Borja, D. et al., 2025
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Lucero-Borja, D. et al., 2025
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Enginyeria Química i Química Analítica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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