DISSOLUTION AND BIOAVAILABILITY OF PHENOBARBITAL IN SOLID DISPERSION WITH PHOSPHATIDYLCHOLINE

The dissolution of phenobarbital (PB) from solid dispersion with phosphatidylcholine (PC) was studied. PB was present in an amorphous state in solid dispersion (PB-PC) if the mole fraction of PB was under 0.75. Thus, supersaturation was observed when an excess amount of PB-PC was dispersed in pH 1.2 and 6.8 media. The degree of supersaturation was largest when the mole fraction of PB was 0.25, although it was only 1.3-fold of the PB solubility in this case. Dissolution from PB-PC was rapid and complete in both pH 1.2 and 6.8 media regardless of the mole fraction of PB, above 90% within 5 min. Biovailability after the oral administration of PB-PC to rabbits with a dose of 15 mg/kg equivalent to PB was compared with that of PB crystals. The area under the plasma concentration curve was bigger, but not significant. The maximum concentration was significantly higher, and the time to maximum concentration was significantly faster. These results indicate that the absorption rate became high with PB-PC because the dissolution was rapid.