Anal Anil K, Stevens Willem F
Bioprocess Technology Program, Asian Institute of Technology, Klong Luang, Bangkok 12120, Thailand.
Int J Pharm. 2005 Feb 16;290(1-2):45-54. doi: 10.1016/j.ijpharm.2004.11.015. Epub 2005 Jan 5.
The aim of this study is to develop multilayer beads with improved properties for controlled delivery of the antibiotic ampicillin. Ionotropic gelation was applied to prepare single and multilayer beads using various combinations of chitosan and Ca(2+) as cationic components and alginate and polyphosphate as anions. Beads prepared with higher concentrations of chitosan entrapped more ampicillin. During incubation in simulated gastric fluid, the beads swelled and started to float but did not show any sign of erosion. Single layer chitosan-alginate beads released 70% of the drug within 4 h. Multilayer beads released only 20-30% in the same period of time. During subsequent incubation in simulated intestinal fluid, both single and multilayer beads continued to release drug. At least part of this release is due to disintegration of the beads. The rate of release both in gastric and intestinal fluid and the kinetics of disintegration in intestinal fluid can be controlled by changing the chitosan concentration in the coagulation fluid. The release of the drug can also be controlled by the degree of cross-linking using polyphosphate. Cross-linked multilayer beads were prepared that released only 40% of the entrapped drug during 24 h. It is concluded that chitosan-alginate multilayer beads, cross-linked with polyphosphate offer an opportunity for controlled gastrointestinal passage of compounds with low molecular weight like ampicillin.
本研究的目的是开发具有改进性能的多层珠，用于抗生素氨苄西林的控释。采用离子凝胶法，以壳聚糖和Ca(2+)的各种组合作为阳离子成分，藻酸盐和多磷酸盐作为阴离子，制备单层和多层珠。用较高浓度壳聚糖制备的珠包封了更多的氨苄西林。在模拟胃液中孵育期间，珠膨胀并开始漂浮，但未显示出任何侵蚀迹象。单层壳聚糖-藻酸盐珠在4小时内释放了70%的药物。多层珠在同一时间段内仅释放20%-30%。在随后的模拟肠液孵育过程中，单层和多层珠都继续释放药物。这种释放至少部分是由于珠的崩解。通过改变凝固液中壳聚糖的浓度，可以控制胃液和肠液中的释放速率以及肠液中的崩解动力学。药物的释放也可以通过使用多磷酸盐的交联程度来控制。制备的交联多层珠在24小时内仅释放40%的包封药物。得出的结论是，用多磷酸盐交联的壳聚糖-藻酸盐多层珠为氨苄西林等低分子量化合物的胃肠道控释提供了机会。
