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| dc.contributor | Universitat de Barcelona |
|---|---|
| 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 | 2016-09-20T17:27:33Z |
| dc.date | 2017-07-21T22:01:17Z |
| dc.date | 2016-07-21 |
| dc.date | 2016-09-20T17:27:38Z |
| dc.identifier.citation | 0928-0987 |
| dc.identifier.citation | 663283 |
| 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 | 14 p. |
| dc.format | application/pdf |
| dc.language.iso | eng |
| dc.publisher | Elsevier B.V. |
| dc.relation | Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.ejps.2016.07.013 |
| dc.relation | European Journal of Pharmaceutical Sciences, 2016, vol. 93, p. 163-176 |
| dc.relation | http://dx.doi.org/10.1016/j.ejps.2016.07.013 |
| dc.rights | cc-by-nc-nd (c) Elsevier B.V., 2016 |
| dc.rights | info:eu-repo/semantics/openAccess |
| dc.rights | http://creativecommons.org/licenses/by-nc-nd/3.0/es |
| dc.subject | Solubilitat |
| dc.subject | Química de superfícies |
| dc.subject | Agents tensioactius |
| dc.subject | Solubility |
| dc.subject | Surface chemistry |
| dc.subject | 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 |
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