大黄素-桂皮醛自微乳的制备及体外评价
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摘要
目的制备大黄素-桂皮醛自微乳,并进行体外评价。方法以油相、乳化剂、助乳化剂用量为影响因素,平均粒径、多分散指数(PDI)、大黄素载药量为评价指标,单纯形网格法优化处方。然后,考察自微乳外观形态、粒径、PDI、Zeta电位、载药量、溶出度。结果最佳处方为油相(肉桂油)用量10%,乳化剂[RH40-吐温80(6∶4)]用量60%,助乳化剂(1,2-丙二醇)用量30%,所得自微乳呈圆球形,大小均匀,平均粒径(17. 5±0. 41)nm,PDI (0. 083±0. 02),Zeta电位(-12. 71±0. 06) m V,大黄素载药量(16. 66±0. 29) mg/g,桂皮醛载药量(91. 36±0. 48) mg/g,20 min内大黄素累积溶出度96. 87%。结论该方法稳定可靠,可用于制备大黄素-桂皮醛自微乳。肉桂油既可作为自微乳中的油相,又可作为药物。
AIM To prepare emodin-cinnamaldehyde self-microemulsions and to make in vitro evaluation.METHODS With consumption of oil phase,emulsifier and co-emulsifier as influencing factors,average particle size,polydispersity index( PDI) and emodin drug loading as evaluation indices,simplex lattice method was applied to optimizing the formulation. Subsequently,the self-microemulsions' appearance and morphology,particle size,PDI, Zeta potential, drug loading and dissolution rate were investigated. RESULTS The optimal formulation was determined to be 10% for oil phase( Cinnamomi Cortex oil) consumption,60% for emulsifier[RH40-Tween 80( 6 ∶ 4) ]consumption,and 30% for co-emulsifier( 1,2-propanediol) consumption. The obtained self-microemulsions were spheroidal with uniform size,demonstrating the average particle size of( 17. 5 ±0. 41) nm,PDI of( 0. 083±0. 02) nm,Zeta potential of(-12. 71±0. 06) m V,emodin drug loading of( 16. 66±0. 29) mg/g,cinnamaldehyde drug loading of( 91. 36 ± 0. 48) mg/g,and accumlative emodin dissolution rate of96. 87% within 20 min. CONCLUSION This stable and reliable method can be used for preparing emodin-cinnamaldehyde self-microemulsions. Cinnamomi Cortex oil can be taken as both oil phase and drug in the self-microemulsions.
AIM To prepare emodin-cinnamaldehyde self-microemulsions and to make in vitro evaluation.METHODS With consumption of oil phase,emulsifier and co-emulsifier as influencing factors,average particle size,polydispersity index( PDI) and emodin drug loading as evaluation indices,simplex lattice method was applied to optimizing the formulation. Subsequently,the self-microemulsions' appearance and morphology,particle size,PDI, Zeta potential, drug loading and dissolution rate were investigated. RESULTS The optimal formulation was determined to be 10% for oil phase( Cinnamomi Cortex oil) consumption,60% for emulsifier[RH40-Tween 80( 6 ∶ 4) ]consumption,and 30% for co-emulsifier( 1,2-propanediol) consumption. The obtained self-microemulsions were spheroidal with uniform size,demonstrating the average particle size of( 17. 5 ±0. 41) nm,PDI of( 0. 083±0. 02) nm,Zeta potential of(-12. 71±0. 06) m V,emodin drug loading of( 16. 66±0. 29) mg/g,cinnamaldehyde drug loading of( 91. 36 ± 0. 48) mg/g,and accumlative emodin dissolution rate of96. 87% within 20 min. CONCLUSION This stable and reliable method can be used for preparing emodin-cinnamaldehyde self-microemulsions. Cinnamomi Cortex oil can be taken as both oil phase and drug in the self-microemulsions.
引文
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[6]刘小美,潘志强,方肇勤,等.均匀设计优选小檗碱、大黄素、桂皮醛抗肝癌最佳配伍的体内研究[J].上海中医药杂志,2018,52(1):77-80.
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[12]赵丹丹,黄挺,黄绳武.依托泊苷过饱和自微乳化释药系统的制备工艺及质量评价研究[J].中草药,2015,46(6):822-831.
[13]李秋萍,戴俊东,翟文文,等.单纯形网格法优化设计姜黄素-胡椒碱复方自微乳制剂处方[J].中国中药杂志,2014,39(20):3936-3944.
[14] Warisnoicharoen W,Lansley A B,Lawrence M J. Nonionic oilin-water microemulsions:the effect of oil type on phase behaviour[J]. Int J Pharm,2000,198(1):7-27.
[15] Rao Z C,Si L Q,Guan Y B,et al. Inhibitive effect of cremophor RH40 or tween 80-based self-microemulsiflying drug delivery system on cytochrome P450 3A enzymes in murine hepatocytes[J]. J Huazhong Univ Sci Technolog Med Sci,2010,30(5):562-568.
[16]祁利平,董艳艳,张景姣,等.复方痛痹舒自微乳基质组成的研究[J].中草药,2017,48(16):3359-3365,3376.
[17]叶蕾,胡容峰,王晓华,等.星点设计-效应面法优化葛根素自微乳工艺[J].中成药,2014,36(3):514-519.
[18]陈笑,富志军.星点设计-效应面法优化莲心总碱自微乳处方[J].中成药,2016,38(7):1490-1495.
[19]杨露,李小芳,罗佳,等.单纯形网格法优选柿叶总黄酮自微乳处方[J].中国实验方剂学杂志,2016,22(24):13-17.
[20]张定堃,傅超美,林俊芝,等.中药制剂的“药辅合一”及其应用价值[J].中草药,2017,48(10):1921-1929.
[2]孙炳文,孙新云.大黄药对的应用[J].河南中医,2008,28(10):87-88.
[3] Wang X Y,Cai S G,Wu Y F,et al. Inhibition of emodin on LPS-induced nitric oxide generation by suppressing PLC-γphosphorylation in rat peritoneal macrophages[J]. Chin Herb Med,2010,2(3):189-194.
[4] Lai J M,Chang J T,Wen C L,et al. Emodin induces a reactive oxygen species-dependent and ATM-p53-Bax mediated cytotoxicity in lung cancer cells[J]. Eur J Pharmacol,2009,623(1-3):1-9.
[5]张利青,张占刚,付岩,等.桂皮醛药理作用的研究进展[J].中国中药杂志,2015,40(23):4568-4572.
[6]刘小美,潘志强,方肇勤,等.均匀设计优选小檗碱、大黄素、桂皮醛抗肝癌最佳配伍的体内研究[J].上海中医药杂志,2018,52(1):77-80.
[7]韩刚,阎林奇,索炜,等.大黄素固体分散体的制备及其溶出度测定[J].中草药,2011,42(3):487-490.
[8] Porter C J H,Wasan K M,Constantinides P. Lipid-based systems for the enhanced delivery of poorly water soluble drugs[J].Adv Drug Deliv Rev,2008,60(6):615-616.
[9]卢秀霞,何琳,陈锦娜,等.丹参酮ⅡA口服自微乳的制备及其体外溶出度评价[J].中草药,2014,45(22):3256-3265.
[10]叶蕾,胡容峰,王晓华,等.星点设计-效应面法优化葛根素自微乳工艺[J].中成药,2014,36(3):514-519.
[11]何选林,王群英. RP-HPLC法同时测定三黄片中7种成分[J].中成药,2017,39(7):1522-1524.
[12]赵丹丹,黄挺,黄绳武.依托泊苷过饱和自微乳化释药系统的制备工艺及质量评价研究[J].中草药,2015,46(6):822-831.
[13]李秋萍,戴俊东,翟文文,等.单纯形网格法优化设计姜黄素-胡椒碱复方自微乳制剂处方[J].中国中药杂志,2014,39(20):3936-3944.
[14] Warisnoicharoen W,Lansley A B,Lawrence M J. Nonionic oilin-water microemulsions:the effect of oil type on phase behaviour[J]. Int J Pharm,2000,198(1):7-27.
[15] Rao Z C,Si L Q,Guan Y B,et al. Inhibitive effect of cremophor RH40 or tween 80-based self-microemulsiflying drug delivery system on cytochrome P450 3A enzymes in murine hepatocytes[J]. J Huazhong Univ Sci Technolog Med Sci,2010,30(5):562-568.
[16]祁利平,董艳艳,张景姣,等.复方痛痹舒自微乳基质组成的研究[J].中草药,2017,48(16):3359-3365,3376.
[17]叶蕾,胡容峰,王晓华,等.星点设计-效应面法优化葛根素自微乳工艺[J].中成药,2014,36(3):514-519.
[18]陈笑,富志军.星点设计-效应面法优化莲心总碱自微乳处方[J].中成药,2016,38(7):1490-1495.
[19]杨露,李小芳,罗佳,等.单纯形网格法优选柿叶总黄酮自微乳处方[J].中国实验方剂学杂志,2016,22(24):13-17.
[20]张定堃,傅超美,林俊芝,等.中药制剂的“药辅合一”及其应用价值[J].中草药,2017,48(10):1921-1929.