Chaurasia M, Chourasia M K, Jain Nitin K, Jain A, Soni V, Gupta Y, Jain S K
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar (M. P.) 470 003, India.
Curr Drug Deliv. 2008 Jul;5(3):215-9. doi: 10.2174/156720108784911668.
In the present work calcium pectinate (Ca-pectinate) microspheres were prepared to deliver methotrexate in the environment of colon. Calcium pectinate microspheres were prepared by modified emulsification method using calcium chloride as cross linker. All the formulations were evaluated for various physicochemical parameters. Particle size of the microspheres was determined using laser diffraction particle size analyzer. Encapsulation efficiency was determined by digesting with enzyme pectinase for 24 hours and swellability by equilibrium swelling in simulated gastrointestinal fluid. The in vitro drug release studies were performed in simulated gastric fluid for 2 hours and simulated intestinal fluid for 3 hours. In vitro release rate studies were also carried out in simulated colonic fluid in presence of rat caecal contents. Moreover, release rate studies were also carried out after enzyme induction by treating the rats with 1 ml of 1% w/v aqueous dispersion of pectin for 7 days. Mean particle size of the microspheres was found to be in the range of 20.82+/-1.34 to 32.26+/-1.59 microm whereas the entrapment efficiency varied from 52.28+/-0.32 to 74.01+/-3.32%. The in vitro drug release studies in simulated gastric fluid and simulated intestinal fluid showed that only 8.15+/-0.49% drug was released in 5 hours whereas most of the loaded drug was released in simulated colonic fluid containing pectinase. In vitro release rate study showed release of 69.94+/-3.46% of drug in presence of 3% rat caecal contents, which was further increased to 94.43+/-4.48% when enzyme induction was carried out for 7 days. Thus, it is concluded that calcium pectinate microspheres can be used to effectively localize the release of drug in the physiological environment of colon.
在本研究中，制备了果胶酸钙（Ca - 果胶酸）微球，用于在结肠环境中递送甲氨蝶呤。采用氯化钙作为交联剂，通过改良乳化法制备果胶酸钙微球。对所有制剂的各种理化参数进行了评估。使用激光衍射粒度分析仪测定微球的粒径。通过用果胶酶消化24小时来测定包封率，并通过在模拟胃肠液中的平衡溶胀来测定溶胀性。体外药物释放研究在模拟胃液中进行2小时，在模拟肠液中进行3小时。还在存在大鼠盲肠内容物的模拟结肠液中进行了体外释放速率研究。此外，在用1 ml 1% w/v果胶水分散液处理大鼠7天进行酶诱导后，也进行了释放速率研究。发现微球的平均粒径在20.82±1.34至32.26±1.59微米范围内，而包封效率在52.28±0.32至74.01±3.32%之间变化。在模拟胃液和模拟肠液中的体外药物释放研究表明，在5小时内仅释放了8.15±0.49%的药物，而大部分负载药物在含有果胶酶的模拟结肠液中释放。体外释放速率研究表明，在存在3%大鼠盲肠内容物的情况下，药物释放率为69.94±3.46%，当进行7天的酶诱导时，该释放率进一步提高到94.43±4.48%。因此，得出结论，果胶酸钙微球可用于在结肠的生理环境中有效地定位药物释放。
