Rai G, Jain S K, Agrawal S, Bhadra S, Pancholi S S, Agrawal G P
Pharmaceutical Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, India.
Pharmazie. 2005 Feb;60(2):131-4.
Microspheres of chitosan hydrochloride (CH) were prepared in order to deliver albendazole specifically into the colon. Microspheres were prepared by an emulsion method using different ratios of drug and CH (1:1 to 1:5), agitation speeds (500 to 1500 rpm) and concentrations of glutaraldehyde in toluene as the cross-linking agent (0.25 to 1.0% w/v). The effect of polymer concentration, stirring rate and concentration of cross-linking agent on the particle size and drug loading was studied. With an increase in CH concentration, the average particle size was increased. Increased agitation speed reduced the size of the microspheres but higher agitation speed resulted in irregularly shaped microspheres. Increasing the concentration of cross-linking agent produced more regularly shaped microspheres of smaller size. The drug loading was highest at a drug: CH ratio of 1:3, stirring speed 1000 rpm and 0.75% w/v concentration of cross-linking agent. The effect of CH concentration on in vitro drug release from the microspheres was evaluated in simulated g.i.t fluids. A comparative in vitro drug release study of the optimized formulation was carried out in simulated colonic fluid, with and without 2% rat caecal content. The drug release in 24 h was 48.9% in colonic fluid without rat caecal content, and 76.5% in colonic fluid with rat caecal contents.
制备了盐酸壳聚糖（CH）微球，以便将阿苯达唑特异性递送至结肠。采用乳液法，使用不同比例的药物与CH（1:1至1:5）、搅拌速度（500至1500转/分钟）以及甲苯中戊二醛作为交联剂的浓度（0.25至1.0%w/v）来制备微球。研究了聚合物浓度、搅拌速率和交联剂浓度对粒径和载药量的影响。随着CH浓度的增加，平均粒径增大。搅拌速度增加会减小微球尺寸，但更高的搅拌速度会导致微球形状不规则。增加交联剂浓度会产生尺寸更小、形状更规则的微球。在药物与CH比例为1:3、搅拌速度为1000转/分钟以及交联剂浓度为0.75%w/v时，载药量最高。在模拟胃肠道液中评估了CH浓度对微球体外药物释放的影响。在有和没有2%大鼠盲肠内容物的模拟结肠液中对优化制剂进行了体外药物释放对比研究。在没有大鼠盲肠内容物的结肠液中，24小时内药物释放率为48.9%，在含有大鼠盲肠内容物的结肠液中为76.5%。
