Marvola Tuuli, Marvola Janne, Kanerva Hanna, Ahonen Aapo, Lindevall Kai, Marvola Martti
Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 University of Helsinki, Finland.
Int J Pharm. 2008 Feb 12;349(1-2):24-9. doi: 10.1016/j.ijpharm.2007.07.033. Epub 2007 Aug 2.
The fate of two colon-specific formulations developed in our previous study was investigated using a gamma scintigraphic imaging method. The formulations contained paracetamol and samarium oxide (Sm2O3) and either microcrystalline cellulose (MCC) or hypromellose (HPMC K4M) as diluent and were coated with Eudragit S polymer. The gamma scintigraphic evaluation proved that the products remained intact in the stomach and the upper gastrointestinal tract. The gastric residence time was less that 1h. Three to four hours after administration the formulations had reached the ileo-caecal junction, i.e. the small intestine transit time was approximately 3h. The capsules disintegrated in the ileo-caecal junction or in the ascending colon. The capsules containing MCC released the marker momentarily, the capsules containing HPMC K4M gradually spreading it to the whole colon. The gamma images also verified that the HPMC gel disintegrates completely in 12-14 h. While comparing the results to those previously obtained from the bioavailability studies it could be concluded that it is possible to develop colon specific drug products that begin releasing the drug in the ileo-caecal junction or at the beginning of the ascending colon and spread the drug dose to a larger surface area by using enteric coats and hydrophilic polymers.
使用γ闪烁成像法研究了我们先前研究中开发的两种结肠特异性制剂的命运。这些制剂含有对乙酰氨基酚和氧化钐（Sm2O3），并以微晶纤维素（MCC）或羟丙甲纤维素（HPMC K4M）作为稀释剂，并用Eudragit S聚合物包衣。γ闪烁成像评估证明，产品在胃和上消化道中保持完整。胃停留时间小于1小时。给药后三到四个小时，制剂到达回盲部，即小肠转运时间约为3小时。胶囊在回盲部或升结肠中崩解。含有MCC的胶囊瞬间释放标记物，含有HPMC K4M的胶囊将其逐渐扩散到整个结肠。γ图像还证实，HPMC凝胶在12-14小时内完全崩解。将结果与先前从生物利用度研究中获得的结果进行比较时，可以得出结论，通过使用肠溶衣和亲水性聚合物，可以开发出在回盲部或升结肠开始时开始释放药物并将药物剂量扩散到更大表面积的结肠特异性药物产品。
