Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C
The ionization constants (pKa) and the pH-dependent solubility (log S-pH) of six phenothiazine derivatives (promazine hydrochloride, chlorpromazine hydrochloride, triflupromazine hydrochloride, fluphenazine dihydrochloride, perphenazine free base, and trifluoperazine dihydrochloride) were determined...
| Autores: | , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/101994 |
| Acceso en línea: | https://hdl.handle.net/2445/101994 |
| Access Level: | acceso abierto |
| Palabra clave: | Solubilitat Química de superfícies Agents tensioactius Solubility Surface chemistry Surface active agents |
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Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°CPobudkowska, AnetaRàfols Llach, ClaraSubirats i Vila, XavierBosch, ElisabethAvdeef, AlexSolubilitatQuímica de superfíciesAgents tensioactiusSolubilitySurface chemistrySurface active agentsThe ionization constants (pKa) and the pH-dependent solubility (log S-pH) of six phenothiazine derivatives (promazine hydrochloride, chlorpromazine hydrochloride, triflupromazine hydrochloride, fluphenazine dihydrochloride, perphenazine free base, and trifluoperazine dihydrochloride) were determined at 25 and 37 °C. The pKa values of these low-soluble surface active molecules were determined by the cosolvent method (n-propanol/water at 37 °C and methanol/water at 25 °C). The log S-pH profiles were measured at 24 h incubation time in 0.15 M phosphate buffers. The log S-pH "shape-template" method, which critically depends on accurate pKa values (determined independently of solubility data), was used to propose speciation models, which were subsequently refined by rigorous mass-action weighted regression procedure described recently. Differential scanning calorimetry (DSC), UV-visible spectrophotometry, potentiometric, and high performance liquid chromatography (HPLC) measurements were used to characterize the compounds. The intrinsic solubility (S0) values of the three least-soluble drugs (chlorpromazine·HCl, triflupromazine·HCl, and trifluoperazine·2HCl) at 25 °C were 0.5, 1.1, and 2.7 μg/mL (resp.). These values increased to 5.5, 9.2, and 8.7 μg/mL (resp.) at the physiological temperature. The enthalpies of solution for the latter compounds were exceptionally high positive (endothermic) values (99-152 kJ·mol− 1). Cationic sub-micellar aggregates were evident (from the distortions in the log S-pH profiles) for chlorpromazine, fluphenazine, perphenazine, and trifluoperazine at 25 °C. The effects persisted at 37 °C for chlorpromazine and trifluoperazine. The solids in suspension were apparently amorphous in cases where the drugs were introduced as the chloride salts.Elsevier B.V.2016201720162016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion14 p.application/pdfhttps://hdl.handle.net/2445/101994Articles publicats en revistes (Enginyeria Química i Química Analítica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: http://dx.doi.org/10.1016/j.ejps.2016.07.013European Journal of Pharmaceutical Sciences, 2016, vol. 93, p. 163-176http://dx.doi.org/10.1016/j.ejps.2016.07.013cc-by-nc-nd (c) Elsevier B.V., 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1019942026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C |
| title |
Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C |
| spellingShingle |
Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C Pobudkowska, Aneta Solubilitat Química de superfícies Agents tensioactius Solubility Surface chemistry Surface active agents |
| title_short |
Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C |
| title_full |
Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C |
| title_fullStr |
Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C |
| title_full_unstemmed |
Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C |
| title_sort |
Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C |
| dc.creator.none.fl_str_mv |
Pobudkowska, Aneta Ràfols Llach, Clara Subirats i Vila, Xavier Bosch, Elisabeth Avdeef, Alex |
| author |
Pobudkowska, Aneta |
| author_facet |
Pobudkowska, Aneta Ràfols Llach, Clara Subirats i Vila, Xavier Bosch, Elisabeth Avdeef, Alex |
| author_role |
author |
| author2 |
Ràfols Llach, Clara Subirats i Vila, Xavier Bosch, Elisabeth Avdeef, Alex |
| author2_role |
author author author author |
| dc.subject.none.fl_str_mv |
Solubilitat Química de superfícies Agents tensioactius Solubility Surface chemistry Surface active agents |
| topic |
Solubilitat Química de superfícies Agents tensioactius Solubility Surface chemistry Surface active agents |
| description |
The ionization constants (pKa) and the pH-dependent solubility (log S-pH) of six phenothiazine derivatives (promazine hydrochloride, chlorpromazine hydrochloride, triflupromazine hydrochloride, fluphenazine dihydrochloride, perphenazine free base, and trifluoperazine dihydrochloride) were determined at 25 and 37 °C. The pKa values of these low-soluble surface active molecules were determined by the cosolvent method (n-propanol/water at 37 °C and methanol/water at 25 °C). The log S-pH profiles were measured at 24 h incubation time in 0.15 M phosphate buffers. The log S-pH "shape-template" method, which critically depends on accurate pKa values (determined independently of solubility data), was used to propose speciation models, which were subsequently refined by rigorous mass-action weighted regression procedure described recently. Differential scanning calorimetry (DSC), UV-visible spectrophotometry, potentiometric, and high performance liquid chromatography (HPLC) measurements were used to characterize the compounds. The intrinsic solubility (S0) values of the three least-soluble drugs (chlorpromazine·HCl, triflupromazine·HCl, and trifluoperazine·2HCl) at 25 °C were 0.5, 1.1, and 2.7 μg/mL (resp.). These values increased to 5.5, 9.2, and 8.7 μg/mL (resp.) at the physiological temperature. The enthalpies of solution for the latter compounds were exceptionally high positive (endothermic) values (99-152 kJ·mol− 1). Cationic sub-micellar aggregates were evident (from the distortions in the log S-pH profiles) for chlorpromazine, fluphenazine, perphenazine, and trifluoperazine at 25 °C. The effects persisted at 37 °C for chlorpromazine and trifluoperazine. The solids in suspension were apparently amorphous in cases where the drugs were introduced as the chloride salts. |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016 2016 2016 2017 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
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article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/101994 |
| url |
https://hdl.handle.net/2445/101994 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.ejps.2016.07.013 European Journal of Pharmaceutical Sciences, 2016, vol. 93, p. 163-176 http://dx.doi.org/10.1016/j.ejps.2016.07.013 |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd (c) Elsevier B.V., 2016 http://creativecommons.org/licenses/by-nc-nd/3.0/es info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd (c) Elsevier B.V., 2016 http://creativecommons.org/licenses/by-nc-nd/3.0/es |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
14 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier B.V. |
| publisher.none.fl_str_mv |
Elsevier B.V. |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Enginyeria Química i Química Analítica) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| reponame_str |
Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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15.811543 |