Kitamori Nobuyuki

Mechanism of drug release from polyglycerol ester of fatty acid-based microspheres

Abstract The factors influencing the drug release and the mechanism of the drug release from the spherical, polyglycerol ester of fatty acid (PGEF)-based microspheres has been elucidated. The release rates of theophylline, phenylpropanolamine hydrochloride (PPA) and prednisolone were examined. The drug release could be regulated by choosing an appropriate hydrophile-lipophile balance value of PGEF. The drug solubility in water affected the release rate of the drug. The particle size of the microspheres did not change during drug release. In addition, the paddle speed did not affect the release rate. Since the release rate could be expressed by Janders equation which considers the change in the interfacial area where the actual release of a solid drug occurs, the release from the microspheres is found to be a diffusion controlled process within the micromatrix.

Bioavailability of 5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione ( ADD-3878) in beagle dogs

Abstract The fundamental pharmacokinetic properties of ADD-3878 were evaluated and the bioavailability of the drug after oral administration was determined in beagle dogs. A pharmacokinetic analysis after intravenous injection of the drug revealed biphasic elimination of the plasma ADD-3878 concentration following a biexponential model with a t 1 2 ,α of 0.27 h and a t 1 2 ,β of 17.11 h. The gastrointestinal absorption of ADD-3878 in solution was significantly faster than those in suspensions. The particle size of ADD-3878 crystals affected both the extent and rate of bioavailability. Furthermore, a significant effect of food on the bioavailability of the drug was observed; the absorption in tablets after food ingestion was approximately double of that in the fasting state. The maximum plasma levels and the areas under the curve at various doses of tablets were proportional to the doses. In a multiple-dose study, there was no unusual accumulation of plasma ADD-3878 concentration.