Abstract
An attempt was made to improve the dissolution behavior of phenytoin (PHT), a poorly watersoluble drug, with phosphatidylcholine (PC) solid dispersion (SD). The powder X-ray diffraction patterns indicated that PHT was present in an amorphous state in SD when the molar fraction of PHT was under 0.33. Infrared spectra suggested a weak interaction, probably hydrogen bonding, between PC and PHT in SD. The solubility of PHT was 30μg/ml in both pH1.2 and 6.8 test solutions. The PHT concentration increased temporarily to 36μg/ml in both pH 1.2 and 6.8 test solutions with SD in which the molar fraction of PHT was 0.25 (SD (0.25)). This is only 1.2 times the PHT solubility, but the dissolution rate in pH 1.2 test solution was significantly improved: the PHT concentration reached 24μg/ml in the first 5min, whereas it was 6μg/ml in the case of PHT crystals. The dissolution rate was slightly higher even with physical mixture (PM) because of improved wettability.
After oral administration of SD (0.25) to rabbits, plasma concentrations up to 8h were significantly higher than those in the cases of PM (0.25) and PHT crystals, but there was no significant difference in the area under the plasma concentration curve. PM (0.25) did not show improved bioavailability. These results were consistent with the results of the dissolution test at pH1.2. PM gave an increased plasma concentration of PHT if PC was used in a large excess over PHT (PM (0.10)), it was considered that PC functioned as an oil in this case.
