热熔挤出技术制备热敏性姜黄素固体分散体的研究
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摘要
目的采用热熔挤出技术制备姜黄素固体分散体,以提高姜黄素的溶解度和溶出度。方法以姜黄素为模型药物,丙烯酸树脂Eudragit E PO(EPO)为载体,溶解度参数法评价药物与载体的相容性。以姜黄素的含量、结晶度和溶出度为评价指标,单因素实验筛选热熔挤出过程中的机筒温度、螺杆转速和冷却速率,优化制备工艺,并与溶剂法和熔融法比较。结合差示扫描量热法、X射线衍射法、傅里叶变换红外光谱法、饱和溶解度测定和体外溶出度试验等对热熔挤出最佳工艺制备的固体分散体进行表征与评价。结果最佳制备工艺:螺杆转速为100 r/min,机筒温度为130~160℃,冷却方式为液氮冷却。此条件下制备的姜黄素固体分散体,药物以无定形态分散在载体中,药物与载体间形成较强的相互作用。结论热熔挤出技术可制备热敏性姜黄素分散体,为采用热熔挤出技术制备热敏性药物固体分散体的研究提供了一定的实验参考。
Objective Hot-melt extrusion technique was applied to prepare curcumin solid dispersions, which can improve the solubility and dissolution of curcumin. Methods Using curcumin as a model drug and Eudragit E PO(EPO) as a carrier, the solubility parameter method was used to evaluate the miscibilty between the drug and the carrier. Taking the content, crystallinity, and dissolution of curcumin as evaluation indicators, the single-factor test was used to select the barrel temperature, screw speed, and cooling rate in the hot-melt extrusion process. The preparation process was optimized and compared with the solvent method and the fusion method. By means of differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, saturated solubility measurement and in vitro dissolution test, the solid dispersions prepared by the best hot-melt extrusion process were characterized and evaluated. Results The best preparation process were as follow: screw speed 100 r/min, barrel temperature 130—160 ℃, and cooling mode of liquid nitrogen cooling. Under such condition, the drug was dispersed in the carrier in an amorphous state, and a strong molecular interaction occurred between the drugs and the carriers. Conclusion Hot-melt extrusion technique can be applied for the preparation of heat-sensitive curcumin dispersions, which provides a certain experimental reference for the preparation of heat-sensitive drug solid dispersions by hot-melt extrusion.
Objective Hot-melt extrusion technique was applied to prepare curcumin solid dispersions, which can improve the solubility and dissolution of curcumin. Methods Using curcumin as a model drug and Eudragit E PO(EPO) as a carrier, the solubility parameter method was used to evaluate the miscibilty between the drug and the carrier. Taking the content, crystallinity, and dissolution of curcumin as evaluation indicators, the single-factor test was used to select the barrel temperature, screw speed, and cooling rate in the hot-melt extrusion process. The preparation process was optimized and compared with the solvent method and the fusion method. By means of differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, saturated solubility measurement and in vitro dissolution test, the solid dispersions prepared by the best hot-melt extrusion process were characterized and evaluated. Results The best preparation process were as follow: screw speed 100 r/min, barrel temperature 130—160 ℃, and cooling mode of liquid nitrogen cooling. Under such condition, the drug was dispersed in the carrier in an amorphous state, and a strong molecular interaction occurred between the drugs and the carriers. Conclusion Hot-melt extrusion technique can be applied for the preparation of heat-sensitive curcumin dispersions, which provides a certain experimental reference for the preparation of heat-sensitive drug solid dispersions by hot-melt extrusion.
引文
[1]牛余萌.姜黄素脂质体的制备及性质研究[D].上海:华东理工大学,2012.
[2]杨雪梅,邱红梅,田蜜,等.姜黄素对人过氧化物酶体增殖物激活受体γ1激活作用的研究[J].中草药,2017,48(15):3122-3126.
[3]郝东明,张丽.姜黄素联合伊立替康对结肠癌SW620细胞的体外抑制作用[J].现代药物与临床,2016,31(6):731-735.
[4]常明向,吴梅梅,李瀚旻.姜黄素与甘草次酸联用对肝癌Hep G-2细胞增殖的抑制作用[J].药物评价研究,2017,40(1):42-47.
[5]姜程曦,吴亮,吴洁,等.姜黄素类似物抑制ERK/JNK以及NF-κB信号通路发挥抗炎活性研究[J].中草药,2016,47(16):2871-2876.
[6]韩伟,雷勇胜.姜黄素治疗泌尿生殖系统癌症的作用机制研究进展[J].现代药物与临床,2016,31(2):260-264.
[7]Zhang D,Luo J Y,Yan D,et al.Effects of two curcuminoids on Candida albicans[J].Chin Herb Med,2012,4(3):205-212.
[8]吴雪梅.姜黄素新剂型:自乳化和亚微乳给药系统的研究[D].福州:福建医科大学,2010.
[9]童晓东,范永春,严玮.姜黄素维生素E聚乙二醇琥珀酸酯-聚乙二醇硬脂酸酯15胶束对姜黄素溶解度和口服生物利用度的影响[J].中草药,2017,48(5):902-906.
[10]Pawar Y B,Shete G,Popat D,et al.Phase behavior and oral bioavailability of amorphous curcumin[J].Eur J Pharm Sci,2012,47(1):56-64.
[11]刘碧林,石明芯,朱照静,等.星点设计-效应面法优化姜黄素正负离子纳米结构脂质载体处方[J].中草药,2016,47(19):3401-3406.
[12]冉娅,张良珂.难溶性药物姜黄素作为纳米晶稳定剂制备Pickering乳剂的研究[J].中草药,2017,48(9):1773-1777.
[13]Li B,Konecke S,Wegiel L A,et al.Both solubility and chemical stability of curcumin are enhanced by solid dispersion in cellulose derivative matrices[J].Carbohyd Polym,2013,98(1):1108-1116.
[14]Wegiel L A,Zhao Y,Mauer L J,et al.Curcumin amorphous solid dispersions:the influence of intra and intermolecular bonding on physical stability[J].Pharm Dev Technol,2013,19(8):976-986.
[15]Chuah A M,Jacob B,Jie Z,et al.Enhanced bioavailability and bioefficacy of an amorphous solid dispersion of curcumin[J].Food Chem,2014,156:227-233.
[16]Meng F,Trivino A,Prasad D,et al.Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersions[J].Eur J Pharm Sci,2015,71:12-24.
[17]何黎黎,袁志翔,郑云,等.姜黄素-介孔二氧化硅纳米粒固体分散体的制备与表征[J].中草药,2016,47(13):2283-2287.
[18]刘娱姗,高署,柯学,等.难溶性药物固体分散体研究新进展[J].药学进展,2013,37(4):166-173.
[19]徐艳,张心怡,狄留庆,等.基于热熔挤出技术的虎杖提取物速释固体分散体制备研究[J].中草药,2017,48(23):4865-4871.
[20]Thakral S,Thakral N K.Prediction of drug-polymer miscibility through the use of solubility parameter based Flory-Huggins interaction parameter and the experimental validation:PEG as model polymer[J].J Pharm Sci,2013,102(7):2254-2263.
[21]Greenhalgh D J,Williams A C,Timmins P,et al.Solubility parameters as predictors of miscibility in solid dispersions[J].J Pharm Sci,1999,88(11):1182-1190.
[22]Xu M,Zhang C,Luo Y,et al.Application and functional characterization of POVACOAT,a hydrophilic co-polymer poly(vinyl alcohol/acrylic acid/methyl methacrylate)as a hot-melt extrusion carrier[J].Drug Dev Ind Pharm,2013,40(1):126-135.
[23]Guo Z,Lu M,Li Y,et al.The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions[J].J Pharm Pharmacol,2014,66(2):285-296.
[2]杨雪梅,邱红梅,田蜜,等.姜黄素对人过氧化物酶体增殖物激活受体γ1激活作用的研究[J].中草药,2017,48(15):3122-3126.
[3]郝东明,张丽.姜黄素联合伊立替康对结肠癌SW620细胞的体外抑制作用[J].现代药物与临床,2016,31(6):731-735.
[4]常明向,吴梅梅,李瀚旻.姜黄素与甘草次酸联用对肝癌Hep G-2细胞增殖的抑制作用[J].药物评价研究,2017,40(1):42-47.
[5]姜程曦,吴亮,吴洁,等.姜黄素类似物抑制ERK/JNK以及NF-κB信号通路发挥抗炎活性研究[J].中草药,2016,47(16):2871-2876.
[6]韩伟,雷勇胜.姜黄素治疗泌尿生殖系统癌症的作用机制研究进展[J].现代药物与临床,2016,31(2):260-264.
[7]Zhang D,Luo J Y,Yan D,et al.Effects of two curcuminoids on Candida albicans[J].Chin Herb Med,2012,4(3):205-212.
[8]吴雪梅.姜黄素新剂型:自乳化和亚微乳给药系统的研究[D].福州:福建医科大学,2010.
[9]童晓东,范永春,严玮.姜黄素维生素E聚乙二醇琥珀酸酯-聚乙二醇硬脂酸酯15胶束对姜黄素溶解度和口服生物利用度的影响[J].中草药,2017,48(5):902-906.
[10]Pawar Y B,Shete G,Popat D,et al.Phase behavior and oral bioavailability of amorphous curcumin[J].Eur J Pharm Sci,2012,47(1):56-64.
[11]刘碧林,石明芯,朱照静,等.星点设计-效应面法优化姜黄素正负离子纳米结构脂质载体处方[J].中草药,2016,47(19):3401-3406.
[12]冉娅,张良珂.难溶性药物姜黄素作为纳米晶稳定剂制备Pickering乳剂的研究[J].中草药,2017,48(9):1773-1777.
[13]Li B,Konecke S,Wegiel L A,et al.Both solubility and chemical stability of curcumin are enhanced by solid dispersion in cellulose derivative matrices[J].Carbohyd Polym,2013,98(1):1108-1116.
[14]Wegiel L A,Zhao Y,Mauer L J,et al.Curcumin amorphous solid dispersions:the influence of intra and intermolecular bonding on physical stability[J].Pharm Dev Technol,2013,19(8):976-986.
[15]Chuah A M,Jacob B,Jie Z,et al.Enhanced bioavailability and bioefficacy of an amorphous solid dispersion of curcumin[J].Food Chem,2014,156:227-233.
[16]Meng F,Trivino A,Prasad D,et al.Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersions[J].Eur J Pharm Sci,2015,71:12-24.
[17]何黎黎,袁志翔,郑云,等.姜黄素-介孔二氧化硅纳米粒固体分散体的制备与表征[J].中草药,2016,47(13):2283-2287.
[18]刘娱姗,高署,柯学,等.难溶性药物固体分散体研究新进展[J].药学进展,2013,37(4):166-173.
[19]徐艳,张心怡,狄留庆,等.基于热熔挤出技术的虎杖提取物速释固体分散体制备研究[J].中草药,2017,48(23):4865-4871.
[20]Thakral S,Thakral N K.Prediction of drug-polymer miscibility through the use of solubility parameter based Flory-Huggins interaction parameter and the experimental validation:PEG as model polymer[J].J Pharm Sci,2013,102(7):2254-2263.
[21]Greenhalgh D J,Williams A C,Timmins P,et al.Solubility parameters as predictors of miscibility in solid dispersions[J].J Pharm Sci,1999,88(11):1182-1190.
[22]Xu M,Zhang C,Luo Y,et al.Application and functional characterization of POVACOAT,a hydrophilic co-polymer poly(vinyl alcohol/acrylic acid/methyl methacrylate)as a hot-melt extrusion carrier[J].Drug Dev Ind Pharm,2013,40(1):126-135.
[23]Guo Z,Lu M,Li Y,et al.The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions[J].J Pharm Pharmacol,2014,66(2):285-296.