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DISOLUCIÓN
La absorción de los fármacos sólidos administrados por
vía oral puede representarse mediante el esquema:
FÁRMACO SÓLIDO
⇩
Kd
FÁRMACO EN SOLUCIÓN EN FLUIDOS GASTROINTESTINALES
⇩
Ka
FÁRMACO EN CIRCULACIÓN SISTÉMICA
Kd y Ka son las constantes de velocidad para los procesos de disolución
y de absorción respectivamente
Solubility determinations
In amber glass bottles was added an excess of NAP at 20 cm3 of each aqueous medium -
regulated solution at pH 7.4 and adjusted to the ionic strength, μ 0.15 mol L-1, which are the
physiological values of the blood (10, 11)- saturated of ROH, MIP or CLF, as the case may
be. Solid-liquid mixtures is stirred in a mechanical shaker Wrist Action, Burrel, model 75 for
an hour. Subsequently, the aqueous dispersions were placed in a thermostatically Magni
Whirl Blue M. Electric Company has stabilised at 40.0 ± 0.05 ºC for at least five days to
reach equilibrium.
After this time, the supernatant solutions were filtered at a constant temperature to
ensure the absence of undissolved particles prior to sampling for analysis. The
concentrations of NAP in saturated solutions were determined by measuring the
respective absorbances after carrying out the appropriate dilutions and interpolating
these values in the calibration curve of UV, uti-using a UV/Vis spectrophotometer
PFU UV2-100 v 4.00 according to a validated methodology (12). Subsequently, the
thermostatically temperature is decreased by 5.0°C and, therefore, stabilized at 35.0
°C for at least two days to allow the precipitation of the excess of the drug is
dissolved.
Once equilibrium is reached, we proceeded to the analysis of the concentration of
the NAP, as previously described. These procedures were developed by decreasing
the temperature of 5.0°C in 5.0°C every time, reaching 20.0°C. All experiments were
done at least in triplicate. To make the conversion of units of concentration between
molarity and mole fraction, it was determined the density of solutions by using a
hydrometer digital DMA 45 Anton Paar.
En la tabla 1 se presentan la estructura molecular y algunas propiedades fisicoquímicas del
NAP. El pKa se corrigió a μ 0,15 mol L–1 mediante la ecuación extendida de Debye-Huckel
(13), considerando el valor presentado por Betageri et al. (14). La temperatura de fusión, la
entalpia de fusión y la entalpia de sublimación fueron reportadas por Perlovich et al. (6).
Este fármaco en solución acuosa actúa principalmente como un ácido de Lewis para
establecer enlaces de hidrogeno con los grupos aceptores de protones en los solventes
(oxígeno en los grupos –OH y >C=O); aunque también puede actuar como base de Lewis,
mediante sus grupos hidroxilo, carbonilo y metoxilo (8).