Akhgari A, Afrasiabi Garekani H, Sadeghi F, Azimaie M
School of Pharmacy and Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Int J Pharm. 2005 Nov 23;305(1-2):22-30. doi: 10.1016/j.ijpharm.2005.08.025. Epub 2005 Oct 19.
The objective of this study was to evaluate the effect of two factors (ratio of Eudragit S100 and Eudragit L100 and the coating level) on indomethacin release from pellets in order to optimize coating formulations for colonic delivery. Coating formulations were designed based on the full factorial design. Two independent variables were the ratio of Eudragit S100:Eudragit L100 (1:4, 1:1 and 1:0) and the level of coating (10%, 15% and 20%, w/w), respectively. The evaluated responses were lag time prior to drug release at pH 6.8 (the time required for drug release up to 2%) and percent of drug release at pH 6.8 in 5h. Polymers were coated onto the pellets containing 20% (w/w) indomethacin, using a fluidized bed coating apparatus. Dissolution test was carried out in media with different pH (1.2, 6.5, 6.8 and 7.2). The dissolution data revealed that the level of coating and the ratio of polymers are very important to achieve optimum formulation. Using responses and resulted statistical equations, optimum formulation consisted of Eudragit S100:L100 in 4:1 ratio and the level of coating (20%) was predicted. Practical results showed that the pellets prepared according to above formulation released no indomethacin at pH 1.2 (simulating stomach pH) and pH 6.5 (simulating proximal part of small intestine pH); drug release was slowly at pH 6.8 (simulating lower part of small intestine pH), but it was fast at pH 7.2 (simulating terminal ileum pH). The results of this study revealed that factorial design is a suitable tool for optimization of coating formulations to achieve colon delivery. It was shown that coating formulation consisted of Eudragit S100:Eudragit L100 in 4:1 ratio at 20% coating level has potential for colonic delivery of indomethacin loaded pellets. The optimized formulation produced dissolution profiles that were close to predicted values.
本研究的目的是评估两个因素（聚丙烯酸树脂S100与聚丙烯酸树脂L100的比例以及包衣水平）对吲哚美辛从微丸中释放的影响，以优化用于结肠给药的包衣制剂。基于全因子设计来设计包衣制剂。两个自变量分别是聚丙烯酸树脂S100:聚丙烯酸树脂L100的比例（1:4、1:1和1:0）以及包衣水平（10%、15%和20%，w/w）。评估的响应指标为在pH 6.8时药物释放前的滞后时间（药物释放至2%所需的时间）以及在pH 6.8时5小时内的药物释放百分比。使用流化床包衣设备将聚合物包衣在含有20%（w/w）吲哚美辛的微丸上。在不同pH（1.2、6.5、6.8和7.2）的介质中进行溶出试验。溶出数据表明，包衣水平和聚合物比例对于获得最佳制剂非常重要。利用响应指标和所得的统计方程，预测最佳制剂为聚丙烯酸树脂S100:L100比例为4:1且包衣水平为20%。实际结果表明，按照上述制剂制备的微丸在pH 1.2（模拟胃pH值）和pH 6.5（模拟小肠近端pH值）时不释放吲哚美辛；在pH 6.8（模拟小肠下部pH值）时药物缓慢释放，但在pH 7.2（模拟回肠末端pH值）时释放迅速。本研究结果表明，因子设计是优化包衣制剂以实现结肠给药的合适工具。结果表明，包衣制剂为聚丙烯酸树脂S100:聚丙烯酸树脂L100比例为4:1且包衣水平为20%时，有潜力用于负载吲哚美辛微丸的结肠给药。优化后的制剂产生的溶出曲线接近预测值。
