Jain Anekant, Gupta Yashwant, Jain Sanjay K
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar, MP, India.
J Drug Target. 2007 May;15(4):285-94. doi: 10.1080/10611860601146134.
A pectin-based colon specific delivery system bearing 5-fluorouracil (5-FU) was developed for effective delivery of drug to the colon. Calcium pectinate gel (CPG) beads were prepared by ionotropic gelation method followed by enteric coating with Eudragit S-100. The CPG beads formed were spherical with smooth surfaces. CPG beads size was found to be in the range of 1.32+/-0 . 12-1.88+/-0.08 mm. The in vitro drug release was investigated using USP dissolution rate test paddle type apparatus in different simulated mediums. Release in PBS (pH 7.4) and simulated gastric fluid showed almost similar pattern and rate, whereas a significant increase in percent cumulative drug release (58.3+/-1.36%) was observed in medium containing rat caecal content, i.e. the amount of the drug released from the formulation was found to be 49.2+/-2.29 and 58.3+/-1.36% of drug with 2 and 4% w/v caecal matter after 24 h whereas in control study 33.2+/-1.19% of drug was released. Moreover, to induce the enzymes that specifically act on pectin, the rats were treated with 1 ml of 1% w/v dispersion of pectin for 2 and 4 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of caecal matter. A marked improvement in the drug release was observed in presence of caecal matter obtained after induction when compared to those without induction. The percentage of drug released after 24 h release was observed to be 69.3+/-2.81 and 86.7+/-3.15%, respectively, with 2 and 4% w/v rat caecal matter obtained after 2 days of enzyme induction, and 82.4+/-3.15 and 98.7+/-4.26%, respectively, after 4 days of enzyme induction. In vivo data showed that Eudragit S-100 coated calcium pectinate beads delivered most of its drug load (93.2+/-3.67%) to the colon after 9 h, which reflects its targeting potential to the colon. It is concluded that orally-administered 5-FU loaded Eudragit S-100 coated calcium pectinate beads can be used effectively for the specific delivery of drug to the colon.
为了实现药物向结肠的有效递送，研发了一种基于果胶的载有5-氟尿嘧啶（5-FU）的结肠特异性递送系统。通过离子凝胶法制备果胶酸钙凝胶（CPG）珠，随后用Eudragit S-100进行肠溶包衣。形成的CPG珠呈球形，表面光滑。发现CPG珠的尺寸在1.32±0.12 - 1.88±0.08毫米范围内。使用USP溶出度试验桨式装置在不同模拟介质中研究体外药物释放。在磷酸盐缓冲液（pH 7.4）和模拟胃液中的释放显示出几乎相似的模式和速率；然而，在含有大鼠盲肠内容物的介质中观察到累积药物释放百分比显著增加（58.3±1.36%），即24小时后，从制剂中释放的药物量分别为含有2%和4%（w/v）盲肠物质的药物的49.2±2.29%和58.3±1.36%，而在对照研究中释放的药物为33.2±1.19%。此外，为了诱导特异性作用于果胶的酶，用1毫升1%（w/v）的果胶分散液对大鼠进行2天和4天的处理，并在存在2%和4%（w/v）盲肠物质的情况下在模拟结肠液中重复释放速率研究。与未诱导的情况相比，在诱导后获得的盲肠物质存在下观察到药物释放有显著改善。在酶诱导2天后获得的2%和4%（w/v）大鼠盲肠物质存在下，24小时释放后观察到的药物释放百分比分别为69.3±2.81%和86.7±3.15%；在酶诱导4天后，分别为82.4±3.15%和98.7±4.26%。体内数据表明，Eudragit S-100包衣的果胶酸钙珠在9小时后将其大部分药物负载（93.2±3.67%）递送至结肠，这反映了其对结肠的靶向潜力。得出的结论是，口服载有5-FU的Eudragit S-100包衣的果胶酸钙珠可有效地用于药物向结肠的特异性递送。
