Hiorth Marianne, Versland Therese, Heikkilä Juha, Tho Ingunn, Sande Sverre Arne
Department of Pharmaceutics, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, N-0316 Oslo, Norway.
Int J Pharm. 2006 Feb 3;308(1-2):25-32. doi: 10.1016/j.ijpharm.2005.10.012. Epub 2005 Dec 1.
This study has investigated the potential of immersion coating calcium containing pellet cores first with pectin, and then with two different cross-linkers, calcium or chitosan. The interaction between pectin and calcium, and between pectin and chitosan, are believed to slow down the drug release, and thereby, the coated pellets might possibly be used for colon specific drug delivery. Both the calcium coated pellets and the chitosan coated pellets had a reduced drug release compared to uncoated pellets in 0.1M HCl (1 h) and phosphate buffer pH 6.8 (4 h). The most successful combination had a drug release of only 17% during the entire test period in comparison to the uncoated pellets that had a drug release of 80%. When chitosan was used as a cross-linker, a higher reduction in drug release was obtained than by using calcium as the cross-linker. For the pellets coated with pectin in combination with chitosan, the type of pectin with a degree of methoxylation (DM) of 35 was superior to the pectin type with DM 17. The drug release was further slowed down by choosing a type of chitosan with a high degree of deacetylation (Dda) 89% and by coating at low concentrations (0.1%) in the immersion solution.
本研究考察了先将含钙微丸芯用果胶包衣,然后再用两种不同交联剂(钙或壳聚糖)包衣的可能性。果胶与钙之间以及果胶与壳聚糖之间的相互作用被认为会减缓药物释放,因此,包衣微丸可能可用于结肠特异性药物递送。与未包衣微丸相比,钙包衣微丸和壳聚糖包衣微丸在0.1M盐酸(1小时)和pH 6.8磷酸盐缓冲液(4小时)中的药物释放均有所降低。最成功的组合在整个测试期间的药物释放率仅为17%,而未包衣微丸的药物释放率为80%。当使用壳聚糖作为交联剂时,与使用钙作为交联剂相比,药物释放的降低幅度更大。对于用果胶与壳聚糖组合包衣的微丸,甲氧基化度(DM)为35的果胶类型优于DM为17的果胶类型。通过选择脱乙酰度(Dda)为89%的壳聚糖类型并在浸泡溶液中以低浓度(0.1%)包衣,药物释放进一步减慢。