Säkkinen Mia, Marvola Janne, Kanerva Hanna, Lindevall Kai, Lipponen Maija, Kekki Tommi, Ahonen Aapo, Marvola Martti
Division of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, University of Helsinki, Helsinki, Finland.
Eur J Pharm Biopharm. 2004 Jan;57(1):133-43. doi: 10.1016/s0939-6411(03)00097-3.
In several reports of in vitro studies it has been suggested that the mucoadhesive chitosans could be of value in preparing gastro-retentive formulations. The aim of this study was to obtain direct in vivo evidence of whether microcrystalline chitosan (MCCh) formulations acted as gastro-retentive systems in humans. Neutron-activation-based gamma scintigraphy was used to study gastric residence times of MCCh granules in healthy male volunteers. Possible effects of neutron irradiation on the properties of the MCCh granules were studied in advance, in vitro. In vivo gamma scintigraphic evaluations were carried out with the subjects in a fasted state, using granules containing 95% (F1) or 40% (F2) of MCCh of molecular weight 150 kDa. Reference formulation (F3) was lactose granules. The reference granules passed rapidly from the stomach (mean t50% 0.5+/-0.3 h (n=5)). MCCh in granules prolonged gastric residence times of the formulations in only a few cases (in one volunteer in the F1 group (n=4) and in two volunteers in the F2 group (n=5)). Maximum individual t50% values were 2.1 h (F1) and 2.3 h (F2). It was concluded that the in vivo mucoadhesion of MCCh formulations is erratic, and that the formulations studied are not reliable gastro-retentive drug delivery systems.
在一些体外研究报告中表明，粘膜粘附性壳聚糖在制备胃滞留制剂方面可能具有价值。本研究的目的是获得微晶壳聚糖（MCCh）制剂在人体中是否作为胃滞留系统的直接体内证据。基于中子活化的γ闪烁显像技术用于研究MCCh颗粒在健康男性志愿者体内的胃滞留时间。预先在体外研究了中子辐照对MCCh颗粒性质的可能影响。对处于禁食状态的受试者使用含有分子量为150 kDa的95%（F1）或40%（F2）的MCCh颗粒进行体内γ闪烁显像评估。参比制剂（F3）为乳糖颗粒。参比颗粒迅速从胃中排出（平均t50%为0.5±0.3小时（n = 5））。MCCh颗粒仅在少数情况下延长了制剂的胃滞留时间（F1组中的一名志愿者（n = 4）和F2组中的两名志愿者（n = 5））。个体最大t50%值分别为2.1小时（F1）和2.3小时（F2）。得出的结论是，MCCh制剂的体内粘膜粘附性不稳定，并且所研究的制剂不是可靠的胃滞留给药系统。
