RESUMEN
Since the bioavailability of the suspension and the tablet of DDB given orally is only 20-30%, we have prepared four kinds of DDB solid dispersion preparations (DDB pilule I with polyethylene glycol 6000 as the vehicle, DDB pilule II with polyethylene glycol 6000 and absorption accelerator as the vehicle, capsule of DDB-urea fusing mixture and DDB-polyvinyl pyrrolidone coprecipitate), and the bioavailability of these preparations were studied in rabbits, rats and human volunteers by HPLC method. All four preparations showed better absorption than the DDB tablet, and the area under serum DDB concentration-time curve of pilule II was 19 fold that of the tablet in rabbits, meaning that the absorption of pilule II is the best of the four preparations. After administration of the four solid dispersion preparations, the fecal excretion of DDB were all lower than the tablet in both animals and human volunteers. The protective action of pilule II against CCl4 hepatotoxicity was about six times stronger than that of the suspensions. Therefore, there are good reasons to use DDB pilule II instead of the tablets of suspension in the clinic.
Asunto(s)
Dioxoles/farmacocinética , Medicamentos Herbarios Chinos/farmacocinética , Animales , Disponibilidad Biológica , Intoxicación por Tetracloruro de Carbono/prevención & control , Cromatografía Líquida de Alta Presión , Dioxoles/administración & dosificación , Formas de Dosificación , Femenino , Humanos , Masculino , Conejos , Ratas , ComprimidosRESUMEN
DDB is poorly soluble in water. The solid dispersions of DDB with easily soluble carriers such as polyethylene glycol 6000 (PEG 6000), polyvinyl pyrrolidone (PVP) and urea were prepared by melting and solvent methods. The two DDB-PEG 6000 systems are thermodynamically stable interstitial solid solutions. The DDB-PVP system is an amorphous precipitate and the DDB-urea system is a simple eutectic physical mixture judged by X-ray diffraction and thermal analysis methods. The dissolution rate of DDB-PEG 6000 pilule and two kinds of DDB tablets were determined. The dissolution rate of DDB-PEG 6000 pilule was found to be faster. The physical dispersion state is an important factor in relation to the dissolution rate of DDB preparations.