1997 年 57 巻 2 号 p. 79-85
The ground or lyophilized mixtures of amphotericin B (AMB) with various polymers were examined in terms of dissolution and bioavailability in oral and rectal administration. The grinding of AMB with polyvinylpyrrolidone (PVP) or sodium caseinate (Na-CSN) decreased the potency of the drug, and the loss of potency in the mixture was greater than that of the drug ground alone. However, some improvement in dissolution by grinding with PVP and Na-CSN was observed. Lyophilization of AMB with PVP or Na-CSN resulted in the highest level of dissolution of the drug. X-ray diffraction patterns indicated that AMB lyophilized with PVP was present in the amorphous state, forming a solid dispersion. The lyophilized mixture of AMB with PVP (1:9, w/w) was administered to rabbits orally or rectally. When administered orally, bioavailability of the lyophilized mixture increased significantly, showing 3.7-fold greater AUC0-24h than that of AMB alone. The extent of bioavailability of suppositories markedly varied in the kind of vehicle. Lyophilization of AMB with PVP was found to be useful for improving the bioavailability of AMB.
