基于相同载体体系的中药成分自乳化制剂的制备及其体外透皮吸收特性考察
|
摘要
目的:制备同时适合于黄芩素、黄连素及大蒜素3种中药成分的自乳化载体体系,并考察这3种自乳化制剂的体外透皮吸收效果。方法:采用饱和溶解度法、伪三元相图法、正交试验筛选最佳的空白处方组成及基质用量。以Franz扩散池和离体大鼠皮肤进行体外透皮吸收试验,采用HPLC分别测定3种自乳化制剂中黄芩素、黄连素及大蒜素的累积透皮渗透量,并分别与黄芩素散剂、黄连素散剂及大蒜素散剂进行比较。结果:最佳处方为油酸乙酯-聚氧乙烯氢化蓖麻油40-聚乙二醇400载体体系,所形成的自乳化制剂粒径适宜,其微观形态呈较规整的球形。透皮吸收10 h,黄芩素、黄连素及大蒜素3种自乳化制剂的药物透皮速率分别为6.898 6,7.600 4,190.040μg·cm~(-2)·h~(-1),累积透皮渗透量分别为71.38,85.54,1 795.16μg·cm~(-2)。结论:成功制备了不同种类中药成分均能使用的自乳化载体体系,且该自乳化制剂的体外透皮吸收效果良好,可为后续中药复方自乳化制剂的制备及其透皮给药吸收研究提供实验依据。
Objective:To prepare self-emulsifying carrier system which was suitable for three Chinese medicinal ingredients(baicalein,berberine and allicin),and investigate transdermal absorption effect in vitro of these three self-emulsifying preparations.Method:The optimum formulation and dosage were screened by the saturated solubility method,pseudo-ternary phase diagram method and orthogonal experiment.Transdermal absorption test in vitro was carried out with excised rats skin and Franz diffusion cell.The cumulative penetration amounts of baicalein,berberine and allicin in the identical self-emulsifying system were determined by HPLC and compared with baicalein powder,berberine powder and allicin powder,respectively.Result:The optimum formulation was ethyl oleate-cremophor RH40-polyethylene glycol(PEG)400.The self-emulsifying preparation had a suitable particle size with a relatively regular spherical shape.At 10 h of transdermal absorption,the transdermal rates of baicalein,berberine and allicin in identical self-emulsifying system were 6.898 6,7.600 4,190.040μg·cm~(-2)·h~(-1),the cumulative penetration amounts of them were 71.38,85.54,1 795.16μg·cm~(-2),respectively.Conclusion:The self-emulsifying carrier system is prepared successfully,which can be used by different kinds of Chinese medicinal ingredients,and the transdermal absorption effect in vitro of these selfemulsifying preparations is good,which can provide experimental basis for the preparation and transdermal absorption of self-emulsifying preparation of Chinese herbal compound.
Objective:To prepare self-emulsifying carrier system which was suitable for three Chinese medicinal ingredients(baicalein,berberine and allicin),and investigate transdermal absorption effect in vitro of these three self-emulsifying preparations.Method:The optimum formulation and dosage were screened by the saturated solubility method,pseudo-ternary phase diagram method and orthogonal experiment.Transdermal absorption test in vitro was carried out with excised rats skin and Franz diffusion cell.The cumulative penetration amounts of baicalein,berberine and allicin in the identical self-emulsifying system were determined by HPLC and compared with baicalein powder,berberine powder and allicin powder,respectively.Result:The optimum formulation was ethyl oleate-cremophor RH40-polyethylene glycol(PEG)400.The self-emulsifying preparation had a suitable particle size with a relatively regular spherical shape.At 10 h of transdermal absorption,the transdermal rates of baicalein,berberine and allicin in identical self-emulsifying system were 6.898 6,7.600 4,190.040μg·cm~(-2)·h~(-1),the cumulative penetration amounts of them were 71.38,85.54,1 795.16μg·cm~(-2),respectively.Conclusion:The self-emulsifying carrier system is prepared successfully,which can be used by different kinds of Chinese medicinal ingredients,and the transdermal absorption effect in vitro of these selfemulsifying preparations is good,which can provide experimental basis for the preparation and transdermal absorption of self-emulsifying preparation of Chinese herbal compound.
引文
[1]Badran M M,Taha E I,Tayel M M,et al. Ultra-fine self nanoemulsifying drug delivery system for transdermal delivery of meloxicam:dependency on the type of surfactants[J]. J Mol Liq,2014,190:16-22.
[2]王钰乐,张永萍.自乳化释药系统及其在难溶性中药成分中的应用[J].贵阳中医学院学报,2016,38(2):95-98.
[3]苏菊,吴朝花,姜丰,等.丹皮酚自微乳经皮给药系统的处方优选及药剂学性质评价[J].中国实验方剂学杂志,2017,23(17):11-16.
[4]辛文妤,宋俊科,何国荣,等.黄芩素和黄芩苷的药理作用及机制研究进展[J].中国新药杂志,2013,22(6):647-653,659.
[5]胡诚毅,莫志贤.黄连素的药理作用及机制研究进展[J].中国实验方剂学杂志,2017,23(20):213-219.
[6]FENG Y H,ZHU X T,WANG Q H,et al. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection[J].Malar J,2012,doi:10. 1186/1475-2875-11-268.
[7]董武军,刘玉玲. HPLC法测定黄芩素静脉注射亚微乳剂的含量[J].药物分析杂志,2009,29(12):2120-2122.
[8]国家药典委员会.中华人民共和国药典.一部[M].北京:中国医药科技出版社,2015:304.
[9]徐云峰,刘清飞,陈曦,等.大蒜素自微乳的制备与质量评价[J].中国新药杂志,2008,17(22):1940-1944.
[10]Ali F R,Shoaib M H,Yousuf R I,et al. Design,development, and optimization of dexibuprofen microemulsion based transdermal reservoir patches for controlled drug delivery[J]. Biomed Res Int,2017,doi:10. 1155/2017/4654958.
[11]Subongkot T,Ngawhirunpat T. Development of a novel microemulsion for oral absorption enhancement of alltrans retinoic acid[J]. Int J Nanomedicine,2017,12:5585-5599.
[12]魏红,付正,陈龙华,等.微乳基质对苦参碱经皮渗透的影响[J].中国医药工业杂志,2010,41(7):513-517.
[13]Singh G,Ghosh B,Kaushalkumar D,et al. Screening of venlafaxine hydrochloride for transdermal delivery:passive diffusion and iontophoresis[J]. AAPS Pharm Sci Tech,2008,9(3):791-797.
[14]Sodalee K,Sapsuphan P,Wongsirikul R,et al.Preparation and evaluation of alpha-mangostin solid selfemulsifying drug delivery system[J]. Asian J Pharm Sci,2016,11(1):225-226.
[15]Dalmora M E,Dalmora S L,Oliveira A G. Inclusion complex of piroxicam withβ-cyclodextrin and incorporation in cationic microemulsion. In vitro drug release and in vivo topical anti-inflammatory effect[J].Int J Pharm,2001,222(1):45-55.
[2]王钰乐,张永萍.自乳化释药系统及其在难溶性中药成分中的应用[J].贵阳中医学院学报,2016,38(2):95-98.
[3]苏菊,吴朝花,姜丰,等.丹皮酚自微乳经皮给药系统的处方优选及药剂学性质评价[J].中国实验方剂学杂志,2017,23(17):11-16.
[4]辛文妤,宋俊科,何国荣,等.黄芩素和黄芩苷的药理作用及机制研究进展[J].中国新药杂志,2013,22(6):647-653,659.
[5]胡诚毅,莫志贤.黄连素的药理作用及机制研究进展[J].中国实验方剂学杂志,2017,23(20):213-219.
[6]FENG Y H,ZHU X T,WANG Q H,et al. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection[J].Malar J,2012,doi:10. 1186/1475-2875-11-268.
[7]董武军,刘玉玲. HPLC法测定黄芩素静脉注射亚微乳剂的含量[J].药物分析杂志,2009,29(12):2120-2122.
[8]国家药典委员会.中华人民共和国药典.一部[M].北京:中国医药科技出版社,2015:304.
[9]徐云峰,刘清飞,陈曦,等.大蒜素自微乳的制备与质量评价[J].中国新药杂志,2008,17(22):1940-1944.
[10]Ali F R,Shoaib M H,Yousuf R I,et al. Design,development, and optimization of dexibuprofen microemulsion based transdermal reservoir patches for controlled drug delivery[J]. Biomed Res Int,2017,doi:10. 1155/2017/4654958.
[11]Subongkot T,Ngawhirunpat T. Development of a novel microemulsion for oral absorption enhancement of alltrans retinoic acid[J]. Int J Nanomedicine,2017,12:5585-5599.
[12]魏红,付正,陈龙华,等.微乳基质对苦参碱经皮渗透的影响[J].中国医药工业杂志,2010,41(7):513-517.
[13]Singh G,Ghosh B,Kaushalkumar D,et al. Screening of venlafaxine hydrochloride for transdermal delivery:passive diffusion and iontophoresis[J]. AAPS Pharm Sci Tech,2008,9(3):791-797.
[14]Sodalee K,Sapsuphan P,Wongsirikul R,et al.Preparation and evaluation of alpha-mangostin solid selfemulsifying drug delivery system[J]. Asian J Pharm Sci,2016,11(1):225-226.
[15]Dalmora M E,Dalmora S L,Oliveira A G. Inclusion complex of piroxicam withβ-cyclodextrin and incorporation in cationic microemulsion. In vitro drug release and in vivo topical anti-inflammatory effect[J].Int J Pharm,2001,222(1):45-55.