Dissociation Constants of Some Carboxylic Acids in Mixed Aqueous Solvents

Yasuda, Mikio

doi:10.1246/bcsj.32.429

Cited by 142 publications

(71 citation statements)

References 5 publications

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“…Each s w pK a result is converted to its respective s s pK a value by use of the appropriate d term. 48 The apparent s s pK a values are then plotted as a function of the reciprocal of the solvent dielectric constant (1/e) (Y-S method) 9,48,56,57 to 0% cosolvent to yield the apparent w w pK a value (I ¼ 50 mM) according to Eq. (4).…”

Section: Pk a Measurementsmentioning

confidence: 99%

“…(3), and extrapolated to 0% cosolvent to yield the apparent w w pK a value using the widely accepted Y-S method. 9,56,57,59 In addition to the aforementioned low solubility compounds, the data set used to evaluate the cosolvent method included 16 additional compounds previously measured with aqueous buffers to further assess the approach. The data set consisted primarily of monobasic compounds with two dibasic compounds (quinacrine and quinine), one acidic compound (flufenamic acid) and one monoacidic/ monobasic zwitterion (mebendazole).…”

Section: Comparison Of Cosolvent Pk a Measurements To Literature Valuesmentioning

confidence: 99%

See 1 more Smart Citation

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Shalaeva

Kenseth²,

Lombardo

et al. 2008

Journal of Pharmaceutical Sciences

186

117

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Section: Pk a Measurementsmentioning

confidence: 99%

Section: Comparison Of Cosolvent Pk a Measurements To Literature Valuesmentioning

confidence: 99%

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Shalaeva

Kenseth²,

Lombardo

et al. 2008

Journal of Pharmaceutical Sciences

186

117

View full text Add to dashboard Cite

“…The ionic strengths of the solutions were set at 0.15 M with KCl. Yasuda-Shedlovsky plots were used to calculate 'aqueous' pK a values [6,7] . Using octanol as the partition solvent, log P values were also determined by potentiometric titration.…”

Section: Pk a And Log P And Log D Determinationmentioning

confidence: 99%

Influence of Ethanol on the Solubility, Ionization and Permeation Characteristics of Ibuprofen in Silicone and Human Skin

Watkinson

Herkenne²,

Guy

et al. 2008

Skin Pharmacol Physiol

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In the context of topical and transdermal delivery, cosolvents may be expected to enhance solubility, modify drug partitioning behaviour and alter skin barrier properties. In the present study, we have investigated systematically the influence of increasing amounts of the cosolvent ethanol on the solubility, ionization, and permeability characteristics of ibuprofen in silicone and in skin. The possibility of ibuprofen self-association was also examined. As the amount of ethanol was raised from 0 to 100%, ibuprofen solubility was enhanced 5,500-fold relative to its aqueous solubility. Up to 50%, the pK_a of ibuprofen shifted from 4.44 to 5.68. Infrared spectroscopy confirmed the presence of ibuprofen in both monomer and dimer forms in vehicles containing 75 and 100% ethanol. In silicone membranes, the flux of ibuprofen increased 8-fold over the range of ethanol concentrations studied (0–100%) relative to aqueous solutions, with the highest flux observed for 100% ethanol. However, in skin, the flux of ibuprofen was optimal for 50:50 and 75:25 ethanol-water vehicles (>10-fold flux enhancement). The lower ibuprofen flux from pure ethanol may reflect the alcohol’s ability to dehydrate human skin. In general, the flux data confirm that increasing ethanol content enhances the solubility of ibuprofen in silicone and human skin as well as in the vehicle itself.

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“…The pK a for sotalol and labetalol DOR/DEM ratio for extensive hydroxylators (8/9 in each were attributed and the pK a of nebivolol (which is not group) was 466 (22-1082) in the control group and 177 soluble in water) was determinated by the Yasuda-(16-3270) in the obese group. The ratios for poor Shedlowsky method [20] with methanol as co-solvent. The hydroxylators (1/9 in each group) were 0.23 (control) and lipophilicity parameters determined or estimated were: 0.70 (obese subject).…”

Section: Ionisation Constants and Lipophilicitymentioning

confidence: 99%

Pharmacokinetics of β‐adrenoceptor blockers in obese and normal volunteers

Cheymol

Poirier

Carrupt

et al. 1997

Brit J Clinical Pharma

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Aims Obesity can modify the pharmacokinetics of lipophilic drugs. As b-adrenoceptor blockers (BB) are often prescribed for obese patients suffering from hypertension or coronary heart disease, this study compares the pharmacokinetics of lipophilic b-adrenoceptor blockers in obese and control subjects. Methods Nine obese (157±24% of ideal body weight (IBW) mean±s.d.) and nine non-obese healthy volunteers (98±10% IBW), aged 32±9 years, were included in the study. Subjects were randomly given a single i.v. infusion of one of the following racemic b-adrenoceptor blockers, whose doses (expressed as base per kg of IBW) were: propranolol (0.108 mg), labetalol (0.99 mg) and nebivolol (0.073 mg ). The plasma concentrations of unchanged drugs were measured by h.p.l.c. The ionisation constants and lipophilicity parameters of b-adrenoceptor blockers were assessed. Results The pharmacokinetic data for the three drugs were qualitatively similar. There was a trend towards a greater total distribution volume (V ss ) in obese patients than in controls. However, V ss expressed per kg body weight was slightly smaller in obese patients. The relationship between V ss and lipophilicity of five b-adrenoceptor was studied by combining the current results with those previously obtained with a moderately lipophilic drug (bisoprolol ) and a hydrophilic one (sotalol). The V ss of the five drugs was positively and well-correlated (r 2 =0.90; P<0.01) with their distribution coefficient at pH 7.4 (log D 7.4 ), but not with their partition coefficients. The linear regression coefficients for lean and obese subjects were very similar. Conclusions Lipophilic b-adrenoceptor blockers seem to diffuse less into adipose than into lean tissues. All electrical forms of the drugs (i.e. cations, neutral forms, or zwitterions) present at physiological pH contribute to their tissue distribution, in both obese and lean subjects.Their tissue distribution in obese patients could be restricted by the sum of hydrophobic forces and hydrogen bonds they elicit with macromolecules in lean tissues.

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Dissociation Constants of Some Carboxylic Acids in Mixed Aqueous Solvents

Cited by 142 publications

References 5 publications

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Measurement of Dissociation Constants (pKa Values) of Organic Compounds by Multiplexed Capillary Electrophoresis Using Aqueous and Cosolvent Buffers**Advanced Analytical Technologies, Inc. (Formerly CombiSep), 2711 South Loop Drive, Suite 4200, Ames, IA 50010.

Influence of Ethanol on the Solubility, Ionization and Permeation Characteristics of Ibuprofen in Silicone and Human Skin

Pharmacokinetics of β‐adrenoceptor blockers in obese and normal volunteers

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