Akiyama Y, Nagahara N, Kashihara T, Hirai S, Toguchi H
DDS Research Laboratories, Takeda Chemical Industries, Ltd., Japan.
Pharm Res. 1995 Mar;12(3):397-405. doi: 10.1023/a:1016208703380.
Two types of polyglycerol ester of fatty acid (PGEF)-based microspheres were prepared: Carbopol 934P (CP)-coated microspheres (CPC-microspheres) and CP-dispersion microspheres (CPD-microspheres). Comparative studies on mucoadhesion were done with these microspheres and PGEF-based microspheres without CP (PGEF-microspheres). In an in vitro adhesion test, the CPD-microspheres adhered strongly to mucosa prepared from rat stomach and small intestine because each CP particle in the CPD-microsphere was hydrated and swelled with part of it remaining within the microsphere and part extending to the surface serving to anchor the microsphere to the mucus layer. The gastrointestinal transit patterns after administration of the CPD-microspheres and PGEF-microspheres to fasted rats were fitted to a model in which the microspheres are emptied from the stomach monoexponentially with a lag time and then transit through the small intestine at zero-order. Parameters obtained by curve fitting confirmed that the gastrointestinal transit time of the CPD-microspheres was prolonged compared with that of the PGEF-microspheres. MRT in the gastrointestinal tract was also prolonged after administration of the CPD-microspheres compared with that following the administration of the PGEF-microspheres.
制备了两种基于聚甘油脂肪酸酯（PGEF）的微球：卡波姆934P（CP）包衣微球（CPC-微球）和CP分散微球（CPD-微球）。对这些微球以及不含CP的基于PGEF的微球（PGEF-微球）进行了黏膜黏附的比较研究。在体外黏附试验中，CPD-微球与大鼠胃和小肠制备的黏膜强烈黏附，因为CPD-微球中的每个CP颗粒都被水合并膨胀，部分留在微球内，部分延伸到表面，有助于将微球锚定在黏液层。将禁食大鼠给予CPD-微球和PGEF-微球后的胃肠道转运模式拟合到一个模型中，即微球以单指数形式从胃中排空，有一个滞后时间，然后以零级速率通过小肠。通过曲线拟合获得的参数证实，与PGEF-微球相比，CPD-微球的胃肠道转运时间延长。与给予PGEF-微球后相比，给予CPD-微球后胃肠道的平均滞留时间也延长。
