超临界CO2抗溶剂法制备姜黄素—EC缓释复合微粒的工艺研究(1)
[摘要]采用超临界CO2抗溶剂法制备具有缓释效果的姜黄素-乙基纤维素(EC)复合微粒。以载药量和回收率为综合评价指标，在单因素的基础上采用正交试验设计优选姜黄素-EC缓释复合微粒的制备工艺，并对优选的工艺组合进行了载药量、回收率、粒径分布、扫描电镜(SEM)、红外光谱(IR)、差示扫描量热法(DSC)以及体外溶出等实验分析。正交试验得到的优选工艺为结晶温度45 ℃，结晶压力10 MPa，姜黄素质量浓度8 g·L-1，溶液体积流量0.9 mL·min-1，动态CO2流出速度4 L·min-1。此工艺条件下，制备的复合微粒的平均载药量和回收率分别为33.01%，83.97%，体积平均粒径为20.632 μm;IR与DSC分析表明姜黄素与EC可能发生了相互作用;体外溶出实验表明姜黄素-EC复合微粒具有良好的缓释效果。超临界CO2抗溶剂法可制备具有缓释效果的姜黄素-EC复合微粒。
[关键词]超临界CO2抗溶剂法;姜黄素-EC;缓释复合微粒;体外溶出
Preparation of curcumin-EC sustained-release composite particles by
, 百拇医药
supercritical CO2 anti-solvent technology
BAI Wei-li， YAN Ting-yuan， WANG Zhi-xiang*， HUANG De-chun， YAN Ting-xuan， LI Ping
(Department of Pharmaceutical Engineering， China Pharmaceutical University， Nanjing 210009， China)
[Abstract]Curcumin-ethyl-cellulose (EC) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading and yield of inclusion complex as evaluation indexes，on the basis of single factor tests， orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experiments such as drug loading， yield， particle size distribution， electron microscope analysis (SEM)， infrared spectrum (IR)， differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows： crystallization temperature 45 ℃， crystallization pressure 10 MPa， curcumin concentration 8 g·L-1， solvent flow rate 0.9 mL·min-1， and CO2 velocity 4 L·min-1. Under the optimal conditions， the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97%， and the average particle size of the particles was 20.632 μm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro dissolution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.
, 百拇医药
[Key words]supercritical CO2 anti-solvent technology; curcumin-ethyl-cellulose; sustained-release composite particles; in vitro dissolution
doi：10.4268/cjcmm20150212
姜黄素(curcumin，CUR)是从姜科植物中提取的具有抗炎、抗癌、降血脂 、抗氧化、抗动脉粥样硬化等药理作用，是价廉、高效、低毒的天然多酚类化合物[1-2]，已被美国国立癌症研究所列为第三代抗癌化学预防药[3]。但CUR水溶性差，口服吸收低，同时药物在体内代谢过快，生物半衰期短，需要每日大剂量频繁给药(每次>8 g·d-1;每日>3次/d)才能维持有效的血药浓度，并对胃肠道有刺激作用，稳定性差，其临床应用受到极大限制。故此，将CUR制成缓释制剂可在一定程度上改善其自身的理化性质和生物活性，并在一定程度上提高药物疗效和稳定性，使药物较长时间保持有效的血药浓度，减少不良反应和服药次数，以期推动姜黄素的临床应用。, 百拇医药(白玮丽 颜亭辕 王志祥 黄德春 颜庭轩 李萍)
[关键词]超临界CO2抗溶剂法;姜黄素-EC;缓释复合微粒;体外溶出
Preparation of curcumin-EC sustained-release composite particles by
, 百拇医药
supercritical CO2 anti-solvent technology
BAI Wei-li， YAN Ting-yuan， WANG Zhi-xiang*， HUANG De-chun， YAN Ting-xuan， LI Ping
(Department of Pharmaceutical Engineering， China Pharmaceutical University， Nanjing 210009， China)
[Abstract]Curcumin-ethyl-cellulose (EC) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading and yield of inclusion complex as evaluation indexes，on the basis of single factor tests， orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experiments such as drug loading， yield， particle size distribution， electron microscope analysis (SEM)， infrared spectrum (IR)， differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows： crystallization temperature 45 ℃， crystallization pressure 10 MPa， curcumin concentration 8 g·L-1， solvent flow rate 0.9 mL·min-1， and CO2 velocity 4 L·min-1. Under the optimal conditions， the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97%， and the average particle size of the particles was 20.632 μm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro dissolution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.
, 百拇医药
[Key words]supercritical CO2 anti-solvent technology; curcumin-ethyl-cellulose; sustained-release composite particles; in vitro dissolution
doi：10.4268/cjcmm20150212
姜黄素(curcumin，CUR)是从姜科植物中提取的具有抗炎、抗癌、降血脂 、抗氧化、抗动脉粥样硬化等药理作用，是价廉、高效、低毒的天然多酚类化合物[1-2]，已被美国国立癌症研究所列为第三代抗癌化学预防药[3]。但CUR水溶性差，口服吸收低，同时药物在体内代谢过快，生物半衰期短，需要每日大剂量频繁给药(每次>8 g·d-1;每日>3次/d)才能维持有效的血药浓度，并对胃肠道有刺激作用，稳定性差，其临床应用受到极大限制。故此，将CUR制成缓释制剂可在一定程度上改善其自身的理化性质和生物活性，并在一定程度上提高药物疗效和稳定性，使药物较长时间保持有效的血药浓度，减少不良反应和服药次数，以期推动姜黄素的临床应用。, 百拇医药(白玮丽 颜亭辕 王志祥 黄德春 颜庭轩 李萍)