Department of Pharmaceutical Technology, EMMA Team, EA 581, School of Pharmacy, 7 boulevard Jeanne d'Arc, University of Bourgogne, 21 079 Dijon Cedex, France.
Int J Pharm. 2011 Jul 29;414(1-2):28-34. doi: 10.1016/j.ijpharm.2011.04.059. Epub 2011 May 12.
Zinc-pectinate beads are interesting drug carriers for oral delivery. In order to investigate their in vitro and in vivo release behaviour, ionotropic gelation was used to entrap theophylline into calcium- or zinc-pectinate beads. Beads were investigated in vitro for their particle properties, especially the release kinetic in different media, and their in vivo pharmacokinetic parameters were tested in rats. Particle size varied between 1.8 and 2.8mm and encapsulation rates between 27 and 30% for Ca- and Zn-pectinate beads, respectively. While Ca-pectinate beads revealed a relative fast disintegration, drug release profiles from Zn-pectinate beads were very much release medium-dependent. Especially, in the presence of phosphate ions, the release from Zn-pectinate beads was blocked at 20% and 40% of the total drug load when tested in phosphate buffer or simulated colonic medium. In vivo Zn-pectinate beads (t(max): 12.0 ± 0.1h) led to a significant lag time for the theophylline absorption compared to Ca-pectinate (t(max): 6.0 ± 2.8h) or free theophylline (t(max): 2.5 ± 2.1h). This delayed release was attributed to the formation of a zinc phosphate coating in vitro and in vivo inducing the retention of theophylline release. Zn-pectinate beads exhibit interesting properties due to its potential as pulsatile delivery system induced by the in situ formation of Zn phosphate, while Ca-pectinate was found to be of limited suitability for controlled release of theophylline.
锌-果胶珠是一种有趣的口服给药药物载体。为了研究其体外和体内释放行为，采用离子凝胶法将茶碱包埋到钙或锌-果胶珠中。在体外研究了珠子的颗粒性质，特别是在不同介质中的释放动力学，并在大鼠体内测试了它们的药代动力学参数。钙离子和锌离子果胶珠的粒径分别在 1.8 至 2.8mm 之间，包封率分别在 27%至 30%之间。虽然钙离子果胶珠显示出相对较快的崩解，但锌离子果胶珠的药物释放曲线非常依赖于释放介质。特别是，在磷酸盐离子存在的情况下，当在磷酸盐缓冲液或模拟结肠介质中测试时，锌离子果胶珠的药物释放被阻滞在 20%和 40%的总药物负荷处。体内锌离子果胶珠（t(max)：12.0±0.1h）与钙离子果胶珠（t(max)：6.0±2.8h）或游离茶碱（t(max)：2.5±2.1h）相比，导致茶碱吸收的明显滞后时间。这种延迟释放归因于锌离子在体外和体内形成磷酸锌涂层，从而导致茶碱释放的滞留。锌离子果胶珠由于其在原位形成锌磷酸盐诱导脉冲释放的潜力而具有有趣的性质，而钙离子果胶珠被发现不太适合茶碱的控制释放。
