Iwanaga Kazunori, Kushibiki Toshihiro, Miyazaki Makoto, Kakemi Masawo
Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Biol Pharm Bull. 2006 Mar;29(3):508-12. doi: 10.1248/bpb.29.508.
Solvent Green 3 (SG), a model poorly water-soluble compound, was orally administered to rats with soybean oil emulsion or the Self-microemulsifying drug delivery system (SMEDDS) composed of Gelucire44/14. The bioavailability of SG after oral administration with SMEDDS was 1.7-fold higher than that with soybean oil emulsion. The intestinal absorption of lipid-based formulations themselves was evaluated by the in situ closed loop method. The effect of lipase and bile salt on their absorption was also evaluated. SMEDDS itself was rapidly absorbed in the intestine even in the absence of lipase and bile salt, and the absorption was increased by the addition of lipase and bile salt. On the other hand, no soybean oil emulsion was absorbed in the absence of lipase and bile salt. However, mixed micelle prepared from emulsion by incubating soybean oil emulsion with lipase and bile salt was rapidly absorbed through the intestine. Without lipase and bile salt, SG was not absorbed after administration with soybean oil emulsion. Therefore, we concluded that the degradation of soybean oil emulsion was needed for SG to be absorbed through the intestine. Furthermore, we investigated the intestinal absorption of SG after oral administration to rats whose chylomicron synthesis were inhibited by pretreatment with colchicine. Colchicine completely inhibited the intestinal absorption of SG after administration with each lipid-based formulation, suggesting that SG was absorbed from the intestine via a lymphatic route. Absorption of the dosage formulation should be paid attention when poorly water-soluble drugs are orally administered with lipid-based formulation.
溶剂绿3（SG）是一种典型的水溶性差的化合物，将其与大豆油乳剂或由Gelucire44/14组成的自微乳化给药系统（SMEDDS）一起口服给予大鼠。与大豆油乳剂相比，用SMEDDS口服给药后SG的生物利用度高1.7倍。采用原位闭环法评估脂质体制剂本身的肠道吸收情况。同时也评估了脂肪酶和胆盐对其吸收的影响。即使在没有脂肪酶和胆盐的情况下，SMEDDS本身也能在肠道中迅速吸收，添加脂肪酶和胆盐后吸收增加。另一方面，在没有脂肪酶和胆盐的情况下，大豆油乳剂不被吸收。然而，通过将大豆油乳剂与脂肪酶和胆盐一起孵育从乳剂中制备的混合微团能迅速通过肠道吸收。在没有脂肪酶和胆盐的情况下，用大豆油乳剂给药后SG不被吸收。因此，我们得出结论，SG要通过肠道吸收需要大豆油乳剂的降解。此外，我们研究了用秋水仙碱预处理抑制乳糜微粒合成的大鼠口服给药后SG的肠道吸收情况。秋水仙碱完全抑制了用每种脂质体制剂给药后SG的肠道吸收，这表明SG是通过淋巴途径从肠道吸收的。当水溶性差的药物与脂质体制剂一起口服给药时，应注意剂型的吸收情况。
