自乳化药物递送系统研究概述
|
摘要
自乳化药物递送系统具有制备简单、减少胃肠道刺激、改善药物口服吸收、提高药物稳定性及生物利用度等优势,常作为解决疏水性和亲脂性药物口服吸收的重要策略。根据近年国内外相关文献,归纳整理自乳化释药系统的处方筛选与优化、质量评价、制剂新技术等内容;分析已上市药物应用情况,探究其发展瓶颈,以期为进一步深入探究自乳化递药系统的发展,自微乳制剂的上市应用提供有价值参考。
Self-emulsifying drug delivery system has the advantages of simple preparation, reduced gastrointestinal irritation,improved oral absorption, improved drug stability and bioavailability, which is often used as an important strategy to solve the oral absorption of hydrophobic and lipophilic drugs. According to the relevant literatures at domestic and foreign in recent years, the optimization of formulation, quality evaluation, and the new technology of preparations of self-emulsifying drug release system were summarized to analyze the application situation of listed drugs and explore its development bottleneck. It is expected to provide valuable reference for further research on the development of self-emulsifying drug delivery system and the marketing application of self-microemulsion preparation.
Self-emulsifying drug delivery system has the advantages of simple preparation, reduced gastrointestinal irritation,improved oral absorption, improved drug stability and bioavailability, which is often used as an important strategy to solve the oral absorption of hydrophobic and lipophilic drugs. According to the relevant literatures at domestic and foreign in recent years, the optimization of formulation, quality evaluation, and the new technology of preparations of self-emulsifying drug release system were summarized to analyze the application situation of listed drugs and explore its development bottleneck. It is expected to provide valuable reference for further research on the development of self-emulsifying drug delivery system and the marketing application of self-microemulsion preparation.
引文
[1]Constantinides P P.Lipid microemulsions for improving drug dissolution and oral absorption:physical and biopharmaceutical aspects[J].Pharm Res,1995,12(11):1561-1572.
[2]Shah N H,Carvajal M T,Patel C I,et al.Self-emulsifying drug delivery systems(SEDDS)with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs[J].Int J Pharm,1994,106(1):15-23.
[3]Armstrong N A,James K C.Drug release from lipidbased dosage forms I[J].Int J Pharm,1980,6(3):195-204.
[4]Pouton C W.Lipid formulations for oral administration of drugs:non-emulsifying,self-emulsifying and'selfmicroemulsifying'drug delivery systems[J].Eur J Pharm Sci,2000,11(Suppl 2):S93-S98.
[5]Pouton C W.Formulation of self-emulsifying drug delivery systems[J].Adv Drug Deliv Rev,1997,25(1):47-58.
[6]Gibaud S,Attivi D.Microemulsions for oral administration and their therapeutic applications[J].Exp Opin Drug Deliv,2012,9(8):937-951.
[7]Pouton C W,Porter C J.Formulation of lipid-based delivery systems for oral administration:materials,methods and strategies[J].Adv Drug Deliv Rev,2008,60(6):625-637.
[8]邹娅,徐应淑,张德华,等.地榆皂苷自乳化药物传递系统的制备及质量评价[J].中草药,2018,49(6):1317-1323.
[9]周立,刘裕红,贾俊.难溶性中药姜黄素自乳化微球的制备及性质考察[J].临床合理用药杂志,2015,8(15):31-33.
[10]杨志欣,张文君,刘明玉,等.三叶豆紫檀苷磷脂复合物自微乳研制及跨膜转运研究[J].中草药,2016,47(4):573-579.
[11]Bhattacharyya A,Bajpai M.Oral bioavailability and stability study of a self-emulsifying drug delivery system(SEDDS)of amphotericin B[J].Curr Drug Deliv,2013,10(5):542-547.
[12]Gu Z,Shi X,Omari-Siaw E,et al.Self-microemulsifying sustained-release pellet of Ginkgo biloba extract:Preparation,invitro,drug release and pharmacokinetics study in beagle dogs[J].J Drug Deliv Sci Technol,2017,37:184-193.
[13]Djekic L,Jankovic J,?alija B,et al.Development of semisolid self-microemulsifying drug delivery systems(SMEDDSs)filled in hard capsules for oral delivery of aciclovir[J].Int J Pharm,2017,528(1):372-380.
[14]Rebello S,Asok A K,Mundayoor S,et al.Surfactants:toxicity,remediation and green surfactants[J].Environ Chem Lett,2014,12(2):275-287.
[15]Cornaire G,Woodley J,Hermann P,et al.Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo[J].Int J Pharm,2004,278(1):119-131.
[16]黄嗣航,龙晓英,袁飞,等.含天然乳化剂的盐酸小檗碱自微乳的制备与体内外性能评价[J].中国新药杂志,2012,21(23):2794-2799.
[17]黄嗣航,龙晓英,袁飞,等.含天然乳化剂的新型葛根素自微乳与传统自微乳体内外性能的对比研究[J].中国药学杂志,2014,49(17):1530-1534.
[18]Vishal P.Self micro-emulsifying drug delivery system:Alipid based drug delivery system[J].Int J Pharm Sci Res,2016,7(2):443-452.
[19]刘丹,张露,张振海,等.银杏黄酮组分自微乳-微丸释药系统的构建[J].中草药,2017,48(16):3377-3383.
[20]杨波,周阳,王福玲,等.纳米载药系统在中药挥发油中的研究进展[J].药学研究,2018,37(1):46-49.
[21]王超,李兆明,苗建武,等.含皂苷的β皂榄香烯自微乳制备工艺的研究[J].中成药,2011,33(3):435-438.
[22]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.
[23]卢秀霞,何琳,陈锦娜,等.丹参酮Ⅱ_A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.
[24]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.
[25]张南生,郭虹,孙卫军,等.Box-Behnken试验设计法优化人参皂苷Rg3自乳化释药系统和质量评价[J].中草药,2015,46(23):3500-3506.
[26]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.
[27]柯秀梅,杨荣平,郭响香,等.自乳化释药系统(SEDDS)对姜黄素类组分增溶作用的研究[J].中草药,2014,45(7):935-941.
[28]陶婉君,李沉纹,尹宗宁.基于定量构效关系设计自乳化系统[J].物理化学学报,2011,27(1):71-77.
[29]刘开萍,程盛勇,郁林娜,等.蜘蛛香总缬草三酯自微乳的制备及质量评价[J].中国实验方剂学杂志,2018,24(11):16-21.
[30]金栋,胡容峰,周安,等.灵芝孢子油自微乳的制备及其质量评价[J].安徽中医药大学学报,2017,36(6):89-92.
[31]Thi T D,Van S M,Barillaro V,et al.Formulate-ability of ten compounds with different physicochemical profiles in SMEDDS[J].J Eur Fed Pharm Sci,2009,38(5):479-488.
[32]蒋瑶,王云红,裴太蓉,等.壳聚糖-海藻酸钠靛玉红自微乳缓释微囊制备、评价及体外释放的研究[J].天然产物研究与开发,2017,29(7):1171-1176.
[33]王可兴,秦翠英,韩静,等.紫杉醇自微乳滴丸的制备及体外释放考察[J].药学实践杂志,2016,34(4):330-333.
[34]Bernkop-Schnürch A,Jalil A.Do drug release studies from SEDDS make any sense?[J].J Contr Rel Offic,2018,271:55-59.
[35]Li F,Hu R,Wang B,et al.Self-microemulsifyingdrug delivery system for improving the bioavailability of huperzine A by lymphaticuptake[J].Acta Pharm Sin,2017(B 7):353-360.
[36]翟雪珍,黄恋琦,刘松,等.雷帕霉素自微乳化释药系统的大鼠在体单向灌流肠吸收[J].中国医院药学杂志,2011,31(3):217-221.
[37]Mamadou G,Charrueau C,Dairou J,et al.Increased intestinal permeation and modulation of presystemic metabolism of resveratrol formulated into selfemulsifying drug delivery systems[J].Int J Pharm,2017,521(1/2):150-155.
[38]Sun C,Gui Y,Hu R,et al.Preparation and pharmacokinetics evaluation of solid selfmicroemulsifying drug delivery system(S-SMEDDS)of osthole[J].Aaps Pharmscitech,2018,19(5):1-10.
[39]孙娟娟,张靖,郭清清,等.固体自微乳载体、固体化方法及稳定性研究进展[J].中国医院药学杂志,2017,37(16):1645-1648,1654.
[40]Cho W,Kim M S,Kim J S,et al.Optimized formulation of solid self-microemulsifying sirolimus delivery systems[J].Int J Nanomed,2013,8(default):1673-1682.
[41]Attama A A,Nzekwe I T,Nnamani P O,et al.The use of solid self-emulsifying systems in the delivery of diclofenac[J].Int J Pharm,2003,262(1/2):23-28.
[42]靖博宇,郑霞,杨瑞,等.中药固体自乳化药物传递系统的发展及应用[J].辽宁中医药大学学报,2014,16(3):214-216.
[43]杨露,李小芳,罗佳,等.柿叶总黄酮自微乳液固压缩片的处方研究[J].中药材,2017,40(3):660-664.
[44]Gao P,Morozowich W.Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs[J].Expert Opin Drug Deliv,2006,3(1):97-110.
[45]严敏嘉,李小芳,吴超群,等.穿心莲内酯过饱和自微乳化释药系统的制备及体外评价[J].中国实验方剂学杂志,2018,24(10):8-14.
[46]Gershanik T,Benita S.Positively charged selfemulsifying oil formulation for improving oral bioavailability of progesterone[J].Pharm Develop Technol,1996,1(2):147-157.
[47]Gershanik T,Haltner E,Lehr C M,et al.Charge-dependent interaction of self-emulsifying oil formulations with Caco-2 cells monolayers:binding,effects on barrier function and cytotoxicity[J].Int J Pharm,2000,211(1):29-36.
[48]Singh B,Bandopadhyay S,Kapil R,et al.Selfemulsifying drug delivery systems(SEDDS):formulation development,characterization,and applications[J].Crit Rev Therap Drug Carr Syst,2009,26(5):427-521.
[49]陈威宇,钱亚芳,谷满仓,等.不同电荷自乳化递药系统对细梗香草皂苷B小肠吸收的研究[J].科技通报,2015,31(11):110-113.
[50]Qi X,Wang L,Zhu J,et al.Self-double-emulsifying drug delivery system(SDEDDS):A new way for oral delivery of drugs with high solubility and low permeability[J].Int Pharm,2011,409(1):245-251.
[51]Wang X,Jiang S,Wang X,et al.Preparation and evaluation of nattokinase-loaded self-double-emulsifying drug delivery system[J].Asian J Pharm Sci,2015,10(5):386-395.
[52]Lv L Z,Tong C Q,Lv Q,et al.Enhanced absorption of hydroxysafflor yellow A using a self-double-emulsifying drug delivery system:in vitro and in vivo studies[J].Int JNanomed,2012,7(default):4099-4107.
[53]徐旖旎,王益,严俊丽,等.阿司匹林磷脂复合物自微乳在大鼠体内的药动学及生物利用度研究[J].中国药房,2017,28(31):4373-4376.
[54]祁利平,董艳艳,张景姣,等.复方痛痹舒自微乳释药系统基质组成的研究[J].中草药,2017,48(16):3359-3365,3376.
[55]CFDA.药品注册进度查询[EB/OL].(2007-11-01)[2018-08-22].http://sq.cfda.gov.cn/datasearch/schedule/search.jsp?tableId=43&tableName=TABLE43&column Name=COLUMN464,COLUMN475&title=%D2%A9%C6%B7%D7%A2%B2%E1%BD%F8%B6%C8%B2%E9%D1%AF.
[2]Shah N H,Carvajal M T,Patel C I,et al.Self-emulsifying drug delivery systems(SEDDS)with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs[J].Int J Pharm,1994,106(1):15-23.
[3]Armstrong N A,James K C.Drug release from lipidbased dosage forms I[J].Int J Pharm,1980,6(3):195-204.
[4]Pouton C W.Lipid formulations for oral administration of drugs:non-emulsifying,self-emulsifying and'selfmicroemulsifying'drug delivery systems[J].Eur J Pharm Sci,2000,11(Suppl 2):S93-S98.
[5]Pouton C W.Formulation of self-emulsifying drug delivery systems[J].Adv Drug Deliv Rev,1997,25(1):47-58.
[6]Gibaud S,Attivi D.Microemulsions for oral administration and their therapeutic applications[J].Exp Opin Drug Deliv,2012,9(8):937-951.
[7]Pouton C W,Porter C J.Formulation of lipid-based delivery systems for oral administration:materials,methods and strategies[J].Adv Drug Deliv Rev,2008,60(6):625-637.
[8]邹娅,徐应淑,张德华,等.地榆皂苷自乳化药物传递系统的制备及质量评价[J].中草药,2018,49(6):1317-1323.
[9]周立,刘裕红,贾俊.难溶性中药姜黄素自乳化微球的制备及性质考察[J].临床合理用药杂志,2015,8(15):31-33.
[10]杨志欣,张文君,刘明玉,等.三叶豆紫檀苷磷脂复合物自微乳研制及跨膜转运研究[J].中草药,2016,47(4):573-579.
[11]Bhattacharyya A,Bajpai M.Oral bioavailability and stability study of a self-emulsifying drug delivery system(SEDDS)of amphotericin B[J].Curr Drug Deliv,2013,10(5):542-547.
[12]Gu Z,Shi X,Omari-Siaw E,et al.Self-microemulsifying sustained-release pellet of Ginkgo biloba extract:Preparation,invitro,drug release and pharmacokinetics study in beagle dogs[J].J Drug Deliv Sci Technol,2017,37:184-193.
[13]Djekic L,Jankovic J,?alija B,et al.Development of semisolid self-microemulsifying drug delivery systems(SMEDDSs)filled in hard capsules for oral delivery of aciclovir[J].Int J Pharm,2017,528(1):372-380.
[14]Rebello S,Asok A K,Mundayoor S,et al.Surfactants:toxicity,remediation and green surfactants[J].Environ Chem Lett,2014,12(2):275-287.
[15]Cornaire G,Woodley J,Hermann P,et al.Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo[J].Int J Pharm,2004,278(1):119-131.
[16]黄嗣航,龙晓英,袁飞,等.含天然乳化剂的盐酸小檗碱自微乳的制备与体内外性能评价[J].中国新药杂志,2012,21(23):2794-2799.
[17]黄嗣航,龙晓英,袁飞,等.含天然乳化剂的新型葛根素自微乳与传统自微乳体内外性能的对比研究[J].中国药学杂志,2014,49(17):1530-1534.
[18]Vishal P.Self micro-emulsifying drug delivery system:Alipid based drug delivery system[J].Int J Pharm Sci Res,2016,7(2):443-452.
[19]刘丹,张露,张振海,等.银杏黄酮组分自微乳-微丸释药系统的构建[J].中草药,2017,48(16):3377-3383.
[20]杨波,周阳,王福玲,等.纳米载药系统在中药挥发油中的研究进展[J].药学研究,2018,37(1):46-49.
[21]王超,李兆明,苗建武,等.含皂苷的β皂榄香烯自微乳制备工艺的研究[J].中成药,2011,33(3):435-438.
[22]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.
[23]卢秀霞,何琳,陈锦娜,等.丹参酮Ⅱ_A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.
[24]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.
[25]张南生,郭虹,孙卫军,等.Box-Behnken试验设计法优化人参皂苷Rg3自乳化释药系统和质量评价[J].中草药,2015,46(23):3500-3506.
[26]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.
[27]柯秀梅,杨荣平,郭响香,等.自乳化释药系统(SEDDS)对姜黄素类组分增溶作用的研究[J].中草药,2014,45(7):935-941.
[28]陶婉君,李沉纹,尹宗宁.基于定量构效关系设计自乳化系统[J].物理化学学报,2011,27(1):71-77.
[29]刘开萍,程盛勇,郁林娜,等.蜘蛛香总缬草三酯自微乳的制备及质量评价[J].中国实验方剂学杂志,2018,24(11):16-21.
[30]金栋,胡容峰,周安,等.灵芝孢子油自微乳的制备及其质量评价[J].安徽中医药大学学报,2017,36(6):89-92.
[31]Thi T D,Van S M,Barillaro V,et al.Formulate-ability of ten compounds with different physicochemical profiles in SMEDDS[J].J Eur Fed Pharm Sci,2009,38(5):479-488.
[32]蒋瑶,王云红,裴太蓉,等.壳聚糖-海藻酸钠靛玉红自微乳缓释微囊制备、评价及体外释放的研究[J].天然产物研究与开发,2017,29(7):1171-1176.
[33]王可兴,秦翠英,韩静,等.紫杉醇自微乳滴丸的制备及体外释放考察[J].药学实践杂志,2016,34(4):330-333.
[34]Bernkop-Schnürch A,Jalil A.Do drug release studies from SEDDS make any sense?[J].J Contr Rel Offic,2018,271:55-59.
[35]Li F,Hu R,Wang B,et al.Self-microemulsifyingdrug delivery system for improving the bioavailability of huperzine A by lymphaticuptake[J].Acta Pharm Sin,2017(B 7):353-360.
[36]翟雪珍,黄恋琦,刘松,等.雷帕霉素自微乳化释药系统的大鼠在体单向灌流肠吸收[J].中国医院药学杂志,2011,31(3):217-221.
[37]Mamadou G,Charrueau C,Dairou J,et al.Increased intestinal permeation and modulation of presystemic metabolism of resveratrol formulated into selfemulsifying drug delivery systems[J].Int J Pharm,2017,521(1/2):150-155.
[38]Sun C,Gui Y,Hu R,et al.Preparation and pharmacokinetics evaluation of solid selfmicroemulsifying drug delivery system(S-SMEDDS)of osthole[J].Aaps Pharmscitech,2018,19(5):1-10.
[39]孙娟娟,张靖,郭清清,等.固体自微乳载体、固体化方法及稳定性研究进展[J].中国医院药学杂志,2017,37(16):1645-1648,1654.
[40]Cho W,Kim M S,Kim J S,et al.Optimized formulation of solid self-microemulsifying sirolimus delivery systems[J].Int J Nanomed,2013,8(default):1673-1682.
[41]Attama A A,Nzekwe I T,Nnamani P O,et al.The use of solid self-emulsifying systems in the delivery of diclofenac[J].Int J Pharm,2003,262(1/2):23-28.
[42]靖博宇,郑霞,杨瑞,等.中药固体自乳化药物传递系统的发展及应用[J].辽宁中医药大学学报,2014,16(3):214-216.
[43]杨露,李小芳,罗佳,等.柿叶总黄酮自微乳液固压缩片的处方研究[J].中药材,2017,40(3):660-664.
[44]Gao P,Morozowich W.Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs[J].Expert Opin Drug Deliv,2006,3(1):97-110.
[45]严敏嘉,李小芳,吴超群,等.穿心莲内酯过饱和自微乳化释药系统的制备及体外评价[J].中国实验方剂学杂志,2018,24(10):8-14.
[46]Gershanik T,Benita S.Positively charged selfemulsifying oil formulation for improving oral bioavailability of progesterone[J].Pharm Develop Technol,1996,1(2):147-157.
[47]Gershanik T,Haltner E,Lehr C M,et al.Charge-dependent interaction of self-emulsifying oil formulations with Caco-2 cells monolayers:binding,effects on barrier function and cytotoxicity[J].Int J Pharm,2000,211(1):29-36.
[48]Singh B,Bandopadhyay S,Kapil R,et al.Selfemulsifying drug delivery systems(SEDDS):formulation development,characterization,and applications[J].Crit Rev Therap Drug Carr Syst,2009,26(5):427-521.
[49]陈威宇,钱亚芳,谷满仓,等.不同电荷自乳化递药系统对细梗香草皂苷B小肠吸收的研究[J].科技通报,2015,31(11):110-113.
[50]Qi X,Wang L,Zhu J,et al.Self-double-emulsifying drug delivery system(SDEDDS):A new way for oral delivery of drugs with high solubility and low permeability[J].Int Pharm,2011,409(1):245-251.
[51]Wang X,Jiang S,Wang X,et al.Preparation and evaluation of nattokinase-loaded self-double-emulsifying drug delivery system[J].Asian J Pharm Sci,2015,10(5):386-395.
[52]Lv L Z,Tong C Q,Lv Q,et al.Enhanced absorption of hydroxysafflor yellow A using a self-double-emulsifying drug delivery system:in vitro and in vivo studies[J].Int JNanomed,2012,7(default):4099-4107.
[53]徐旖旎,王益,严俊丽,等.阿司匹林磷脂复合物自微乳在大鼠体内的药动学及生物利用度研究[J].中国药房,2017,28(31):4373-4376.
[54]祁利平,董艳艳,张景姣,等.复方痛痹舒自微乳释药系统基质组成的研究[J].中草药,2017,48(16):3359-3365,3376.
[55]CFDA.药品注册进度查询[EB/OL].(2007-11-01)[2018-08-22].http://sq.cfda.gov.cn/datasearch/schedule/search.jsp?tableId=43&tableName=TABLE43&column Name=COLUMN464,COLUMN475&title=%D2%A9%C6%B7%D7%A2%B2%E1%BD%F8%B6%C8%B2%E9%D1%AF.