Solubility of Doxycycline in Aqueous Solution

Bogardus, Joseph B.; Blackwood, Robert K.

doi:10.1002/jps.2600680218

Cited by 101 publications

(73 citation statements)

References 13 publications

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“…It may be that the sub-micellar aggregation with the leastsoluble molecules has an impact on the heats of dissolution based on the two-temperature results reported here. This is consistent with observations of others, that the solubility of drugs prone to the forming aggregates can be strongly dependent on temperature (Bogardus and Blackwood, 1979).…”

Section: Phenothiazine Thermodynamicssupporting

confidence: 94%

“…There are only a handful of other examples of sub-micellar aggregation (Higuchi et al, 1953;Bogardus and Blackwood, 1979;Serajuddin and Rosoff, 1984;Serajuddin and Jarowski, 1985;Fini et al, 1995;Zhu and Streng, 1996;Ledwidge and Corrigan, 1998;Jinno et al, 2000). In the above examples, the stoichiometries of aggregation were estimated from the re-analysis of published solubility-pH data (Avdeef 2007(Avdeef , 2012; Völgyi et al, 2013;Avdeef, 2014a,b;Butcher et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Phenothiazines solution complexity – Determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C

Pobudkowska

Ràfols

Subirats

et al. 2016

European Journal of Pharmaceutical Sciences

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The ionization constants (pK a ) 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 o C. The pK a values of these low-soluble surface active molecules were determined by the cosolvent method (n-propanol/water at 37 o C and methanol/water at 25 o 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 pK a 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 (S 0 ) values of the three least-soluble drugs (chlorpromazine·HCl, triflupromazine·HCl, and trifluoperazine·2HCl) at 25 o 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 o C. The effects persisted at 37 o C for chlorpromazine and trifluoperazine. The solids in suspension were apparently amorphous in cases where the drugs were introduced as the chloride salts.3

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Section: Phenothiazine Thermodynamicssupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Phenothiazines solution complexity – Determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C

Pobudkowska

Ràfols

Subirats

et al. 2016

European Journal of Pharmaceutical Sciences

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show abstract

“…Up to three different solids could be tested in a single calculation. The presence of particular species was suggested by the slope characteristics of the log S -pH curve [1,5,[7][8][9][10][11].…”

Section: Refinement Of Intrinsic and Salt Solubility And Aggregation mentioning

confidence: 99%

“…There are numerous reports of aggregation forming systems [1,[5][6][7][8][9][10][11][12]. For example, doxycycline [8], with intrinsic solubility S 0 0.72 mg•mL -1 , at 25 °C in 1 M NaCl/HCl acidic solutions, forms dimers with K 2 = 24 M -1 .…”

Section: Introductionmentioning

confidence: 99%