Mäki Riikka, Suihko Eero, Korhonen Ossi, Pitkänen Heli, Niemi Riku, Lehtonen Marko, Ketolainen Jarkko
Department of Pharmaceutics, University of Kuopio, Kuopio, Finland.
Eur J Pharm Biopharm. 2006 Feb;62(2):163-70. doi: 10.1016/j.ejpb.2005.07.009. Epub 2005 Dec 15.
The aim of this study was to design site specific, controlled release tablets of N-acetyl-d-glucosamine (NAG), maltose monohydrate and maltopentaose by using hydrophobic matrix formers starch acetate (SA) and ethyl cellulose (EC). The optimized matrices, which had either low porosity and high drug load or high porosity and low drug load, released the saccharides within the desired 2-4 h. In general, it was possible to control the release rate of saccharides by altering the relative amount of hydrophobic matrix former in the tablet and tablet porosity. The release type of saccharides from these formulations varied from immediate release to sustained release. In the case of sustained release formulations, it was found that the release of maltose monohydrate and maltopentaose was biphasic and slower than the release rate of NAG from similar tablets. NAG release kinetics followed square root of time kinetics, while in the case of maltose monohydrate and maltopentaose, the release kinetics were zero order in both phases. The biphasic dissolution profile was proposed to be caused by water mediated recrystallisation of the disordered material formed during the dissolution. Both SA and EC matrices were found to represent suitable controlled oral delivery vehicles for saccharides.
本研究的目的是通过使用疏水性基质形成剂醋酸淀粉(SA)和乙基纤维素(EC)来设计N-乙酰-d-葡萄糖胺(NAG)、一水麦芽糖和麦芽五糖的位点特异性控释片剂。优化后的基质,要么具有低孔隙率和高载药量,要么具有高孔隙率和低载药量,能在2-4小时的预期时间内释放糖类。一般来说,通过改变片剂中疏水性基质形成剂的相对量和片剂孔隙率,可以控制糖类的释放速率。这些制剂中糖类的释放类型从速释到缓释不等。在缓释制剂的情况下,发现一水麦芽糖和麦芽五糖的释放是双相的,且比类似片剂中NAG的释放速率慢。NAG的释放动力学遵循时间平方根动力学,而对于一水麦芽糖和麦芽五糖,两个阶段的释放动力学均为零级。有人提出,双相溶解曲线是由溶解过程中形成的无序材料的水介导重结晶引起的。SA和EC基质均被发现是糖类合适的口服控释载体。