The acid-base equilibria of a diprotic, slightly hydrosoluble base ketoconazole were studied in homogeneous and heterogeneous water systems. The determinations were performed at 25?C at a constant ionic strength of M(NaCl). The acidity constant Ka1 was determined by potentiometric (pKa1 3.20) and spectrophotometric (pKa1 3.26) methods. A pKa2 constant of 6.10 was obtained based on the equilibrium constants pKs0 4.84 and pKs1 -1.26, determined in a heterogeneous ketoconazole system. The obtained values of the constants served to calculate the solubility and the distribution of the equilibrium forms of ketoconazole as a function of pH. On the basis of the distribution of the equilibrium forms of ketoconazole, a spectrophotometric method for the determination of its content in commercial tablets was developed. The determinations were performed at 225 nm in 0.1 M HCl. The method is simple and rapid and enables the direct spectrophotometric determination of the content of ketoconazole without previous isolation.
For a series of seven unsaturated and seven epoxy di-and tricarboxylic acids, pK a a values were determined potentiometrically in aqueous media at 25 °C and an ionic strength of 0.1 M (NaCl). The thermodynamic pK a a values were correlated with the atomic charges of carboxylic group calculated by the MNDO-PM3 semiempirical MO method.
Buffers type I (sparingly soluble molecular acid, HA) Buffers type I1 (sparingly soluble molecular base, A) Buffer curves: theoretical considerations Practical aspects Effect of dilution Buffer curves: theoretical considerations Buffers type I (sparingly soluble molecular acid, H2A) Buffers type I1 (sparingly soluble molecular base, A)
Acidbase equilibria in heterogeneous and homogeneous systems of some sparingly soluble benzodiazepines (diazepam, prazepam, chlordiazepoxide and medazepam) were investigated in aqueous solution and the corresponding equilibrium constants were determined by the application of pH-metric, spectrophotometric and solubility methods. The sites of protonation were predicted on the basis of the analysis of the corresponding carbon-I3 nuclear magnetic resonance spectra. In addition, buffer characteristics of saturated aqueous solutions of these drugs in the presence of the solid phase were investigated and it was established that they possess a very high buffer capacity over a specific pH range.
Protolytic equilibria of midazolam in the pH range 0-12 were investigated. Acidity, hydrolysis, equilibrium constants in the heterogeneous system and the solubility of midazolam were determined [I = 0.1 moll-1 (NaCI), 25 "C]. A spectrophotometric method was developed for the investigation of the mechanism of hydrolysis and the determination of the corresponding equilibrium constants. In addition, buffer characteristics of the two-phase and single-phase midazolam buffers were investigated.
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