基于转矩流变性的中药微丸润湿剂用量筛选研究(1)
[摘要] 挤出滚圆法制备中药微丸过程中，同时具有润滑作用和黏合作用的润湿剂，其用量直接影响软材、挤出物的性质，进而影响微丸的成型质量。本研究选择具有代表性的25种单味中药作为模型药物，以MCC为成球剂，设定20%，30%，40% 3个载药量，共75种制剂原料，测定转矩流变曲线，获得最大转矩(Tmax)及对应的加水量(WTmax)，并在其指导的加水量条件下挤出、滚圆。结果表明，对于75种含中药的制剂原料，在转矩流变性曲线第2个最大转矩力所对应的加水量(WTmax2)条件下得到圆球的制剂原料共有74个，提示MTR可用于指导中药微丸最佳润湿剂用量的优选。转矩流变仪不仅可用于指导挤出滚圆法制备纯MCC微丸的最佳润湿剂用量筛选，也可用于指导含中药提取物微丸的最佳润湿剂用量筛选，在制备中药微丸时，可减少大量的预实验。
[关键词] 挤出滚圆法； 中药微丸； 润湿剂； 转矩流变仪
Wetting agent dosage screening for traditional Chinese medicine
, 百拇医药
pellet based on torque rheological property
LI Xue1， HONG Yanlong1，2*， XIAN Jiechen2， FENG Yi2， ZHENG Yaping2， CHU Shici2
(1. Shanghai Innovation Center of Traditional Chinese Medicine Health Service， Shanghai University of
Traditional Chinese Medicine， Shanghai 201203， China
2. Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine， Ministry of Education，Shanghai University of Traditional Chinese Medicine， Shanghai 201203， China)
, http://www.100md.com
[Abstract] With lubricant and bonding effect simultaneously， wetting agent has direct effect on properties of wet mass and extrudate， thus affecting the forming quality of pellets in extrusionspheronization process. In this research， 25 representative kinds of traditional Chinese medicine(TCM) were selected as model drugs and 20%， 30% and 40% drug loading were set with MCC as their balling agent. The torque rheological curves were measured to get parameters such as maximum torque (Tmax) and corresponding water addition (WTmax) for these 75 raw materials by a mixer torque rheometer (MTR).The results showed that among 75 representative raw materials， 74 ones could be obtained for spherical pellets under the water addition of WTmax2. corresponding to the second largest torque in torque rheological curve， suggesting that MTR could be used to select the optimal wetting agent dosage of TCM pellets. So the tedious and expensive preproduction work could be considerably reduced when TCM pellets were prepared.
, http://www.100md.com
[Key words] extrusionspheronization； traditional Chinese medicine (TCM) pellet； wetting agent； mixer torque rheometer
擠出滚圆法制备微丸时，润湿剂的加入能够在物料粒子间形成液桥，并在挤出滚圆过程中起到润滑剂和黏合剂的作用，润湿剂的极性、表面张力、黏度是其发挥润湿作用的主要原因[1]，故润湿剂的用量筛选在挤出滚圆法制备微丸过程中起到关键性作用[2]。转矩流变性是指制剂原料加入润湿剂后，受外界剪切力作用时发生的混合、流动及与外界作用力对抗的性质，可通过混合转矩流变仪(mixer torque rheometry，MTR)测定，随着加水量的增加以及高速混合，水分子在颗粒间迁移，将呈现钟摆状、索带状、毛细管状以及连续液滴状的变化[34]，见图1。混合转矩流变仪可有效、准确地指导以MCC为主的制剂原料的润湿剂用量范围选择，目前被广泛应用在制剂领域[56]。
国外研究表明，以MCC为主的制剂原料，当其处于毛细管状时，转矩力最大，物料湿度适宜，微丸质量较好。研究者以MCC为原料，通过MTR测定软材的转矩流变曲线，可预测软材的最适润湿剂用量[3]、微丸质量[78]，确定制剂原料的混合终点[9]，以及评价制备软材所需辅料的性能[1011]。Kristensen等[12]研究发现在80%MCC的处方中，软材的平均转矩力与微丸粒径之间存在线性关系；Ibrahim[13]认为，在较大的Tmax对应的加水量制备所得微丸粒径较大；Chatlapalli[14]比较2种不同型号羟丙甲纤维素的转矩力行为，发现峰值宽度越宽，适宜加水量范围越大，因此更易选择获得理想微丸的润湿剂用量。, http://www.100md.com(李雪 洪燕龙 鲜洁晨 冯怡 郑亚平 楚世慈)
[关键词] 挤出滚圆法； 中药微丸； 润湿剂； 转矩流变仪
Wetting agent dosage screening for traditional Chinese medicine
, 百拇医药
pellet based on torque rheological property
LI Xue1， HONG Yanlong1，2*， XIAN Jiechen2， FENG Yi2， ZHENG Yaping2， CHU Shici2
(1. Shanghai Innovation Center of Traditional Chinese Medicine Health Service， Shanghai University of
Traditional Chinese Medicine， Shanghai 201203， China
2. Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine， Ministry of Education，Shanghai University of Traditional Chinese Medicine， Shanghai 201203， China)
, http://www.100md.com
[Abstract] With lubricant and bonding effect simultaneously， wetting agent has direct effect on properties of wet mass and extrudate， thus affecting the forming quality of pellets in extrusionspheronization process. In this research， 25 representative kinds of traditional Chinese medicine(TCM) were selected as model drugs and 20%， 30% and 40% drug loading were set with MCC as their balling agent. The torque rheological curves were measured to get parameters such as maximum torque (Tmax) and corresponding water addition (WTmax) for these 75 raw materials by a mixer torque rheometer (MTR).The results showed that among 75 representative raw materials， 74 ones could be obtained for spherical pellets under the water addition of WTmax2. corresponding to the second largest torque in torque rheological curve， suggesting that MTR could be used to select the optimal wetting agent dosage of TCM pellets. So the tedious and expensive preproduction work could be considerably reduced when TCM pellets were prepared.
, http://www.100md.com
[Key words] extrusionspheronization； traditional Chinese medicine (TCM) pellet； wetting agent； mixer torque rheometer
擠出滚圆法制备微丸时，润湿剂的加入能够在物料粒子间形成液桥，并在挤出滚圆过程中起到润滑剂和黏合剂的作用，润湿剂的极性、表面张力、黏度是其发挥润湿作用的主要原因[1]，故润湿剂的用量筛选在挤出滚圆法制备微丸过程中起到关键性作用[2]。转矩流变性是指制剂原料加入润湿剂后，受外界剪切力作用时发生的混合、流动及与外界作用力对抗的性质，可通过混合转矩流变仪(mixer torque rheometry，MTR)测定，随着加水量的增加以及高速混合，水分子在颗粒间迁移，将呈现钟摆状、索带状、毛细管状以及连续液滴状的变化[34]，见图1。混合转矩流变仪可有效、准确地指导以MCC为主的制剂原料的润湿剂用量范围选择，目前被广泛应用在制剂领域[56]。
国外研究表明，以MCC为主的制剂原料，当其处于毛细管状时，转矩力最大，物料湿度适宜，微丸质量较好。研究者以MCC为原料，通过MTR测定软材的转矩流变曲线，可预测软材的最适润湿剂用量[3]、微丸质量[78]，确定制剂原料的混合终点[9]，以及评价制备软材所需辅料的性能[1011]。Kristensen等[12]研究发现在80%MCC的处方中，软材的平均转矩力与微丸粒径之间存在线性关系；Ibrahim[13]认为，在较大的Tmax对应的加水量制备所得微丸粒径较大；Chatlapalli[14]比较2种不同型号羟丙甲纤维素的转矩力行为，发现峰值宽度越宽，适宜加水量范围越大，因此更易选择获得理想微丸的润湿剂用量。, http://www.100md.com(李雪 洪燕龙 鲜洁晨 冯怡 郑亚平 楚世慈)