Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/101994
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Pobudkowska, Aneta | - |
dc.contributor.author | Ràfols Llach, Clara | - |
dc.contributor.author | Subirats i Vila, Xavier | - |
dc.contributor.author | Bosch, Elisabeth | - |
dc.contributor.author | Avdeef, Alex | - |
dc.date.accessioned | 2016-09-20T17:27:33Z | - |
dc.date.available | 2017-07-21T22:01:17Z | - |
dc.date.issued | 2016-07-21 | - |
dc.identifier.issn | 0928-0987 | - |
dc.identifier.uri | http://hdl.handle.net/2445/101994 | - |
dc.description.abstract | 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. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier B.V. | - |
dc.relation.isformatof | Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.ejps.2016.07.013 | - |
dc.relation.ispartof | European Journal of Pharmaceutical Sciences, 2016, vol. 93, p. 163-176 | - |
dc.relation.uri | http://dx.doi.org/10.1016/j.ejps.2016.07.013 | - |
dc.rights | cc-by-nc-nd (c) Elsevier B.V., 2016 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es | - |
dc.source | Articles publicats en revistes (Enginyeria Química i Química Analítica) | - |
dc.subject.classification | Solubilitat | - |
dc.subject.classification | Química de superfícies | - |
dc.subject.classification | Agents tensioactius | - |
dc.subject.other | Solubility | - |
dc.subject.other | Surface chemistry | - |
dc.subject.other | Surface active agents | - |
dc.title | Phenothiazines solution complexity - determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 663283 | - |
dc.date.updated | 2016-09-20T17:27:38Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 27449396 | - |
Appears in Collections: | Articles publicats en revistes (Enginyeria Química i Química Analítica) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
663283.pdf | 3.82 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License