Dissolution and Bioavailability of Phenytoin in Solid Dispersion with phosphatidylcholine

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An attempt was made to improve the dissolution behavior of phenytoin(PHY), a poorly water-soluble 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 30 μg/ml in both pH 1.2 and 6.8 test solutions. The PHT concentration increased temporarily to 36 μg/m 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 24 μg/ml in the first 5 min, whereas it was 6 μg/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 sp to 8 h 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 pH 1.2. 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.
社団法人日本薬学会の論文
1988-12-25

Dissolution and Bioavailability of Phenytoin in Solid Dispersion with phosphatidylcholine

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