热熔压敏胶基质结构对药物释放性能的影响
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摘要
为了研究热熔压敏胶基质结构对药物的释放性能的影响,实验中以不同牌号的苯乙烯-异戊二烯-苯乙烯嵌段聚合物为主体材料,制备了具有不同结构的压敏胶基质。同时选择了水杨酸甲酯、辣椒素、盐酸苯海拉明为模型药物,考察了药物在不同基质中的释放行为。研究结果表明,药物在基质中以分散或溶解状态分布,浓度为2%时无结晶析出。药物在基质中的扩散决定了药物的释放速率。对于不同药物,在基质中溶解度大,药物的扩散系数高,则释放速率快。对于同种药物在不同基质中的释放,软硬两相分布均匀的嵌段聚合物能够提供较多的自由体积,由其制备的基质具有较低的储能模量平台和较低的黏度,可以提高药物在基质中的扩散系数,导致释放速率加快。
In order to investigate the effect of matrix structure on drug release profiles, hot-melt pressure sensitive adhesives were made with different styrene-isoprene-styrene block copolymers. Methyl salicylate, capsaicin, and diphenhydramine hydrochloride were selected as model drugs to perform the release experiment. The result shows that the drugs exist in a dispersed or dissolved state in the matrix and no crystallization occurs with the drug concentration up to 2 %. The drug release profile is controlled by the diffusion mechanism in the matrix. The drug with high solubility in the matrix gives a high diffusion coefficient, and leads to have a fast release behaviors. On the other hand, the block copolymer with homogeneous and mesh-like microstructures possesses more free volume of intermolecular, which causes the reduction of the energy storage modulus and viscosity of the matrix and results in a higher diffusion rate of the drugs.
In order to investigate the effect of matrix structure on drug release profiles, hot-melt pressure sensitive adhesives were made with different styrene-isoprene-styrene block copolymers. Methyl salicylate, capsaicin, and diphenhydramine hydrochloride were selected as model drugs to perform the release experiment. The result shows that the drugs exist in a dispersed or dissolved state in the matrix and no crystallization occurs with the drug concentration up to 2 %. The drug release profile is controlled by the diffusion mechanism in the matrix. The drug with high solubility in the matrix gives a high diffusion coefficient, and leads to have a fast release behaviors. On the other hand, the block copolymer with homogeneous and mesh-like microstructures possesses more free volume of intermolecular, which causes the reduction of the energy storage modulus and viscosity of the matrix and results in a higher diffusion rate of the drugs.
引文
[1]Galán C,Sierra C A,Gómez Fatou J M,et al.A Hot-melt pressure-sensitive adhesive based on styrene-butadiene-styrene rubber.The effect of adhesive composition on the properties[J].J Appl Polym Sci,1996,62(8):1263-1275.
[2]WANG Cheng-xiao(王承潇),TANG Xiu-zhen(汤秀珍),SHEN Ping-niang(沈平孃),et al.Advances in studies on hot melt pressure sensitive applied in patches of Chinese materia medica(热熔压敏胶应用于中药贴剂的研究进展)[J].Chinese Traditional and Herbal Drugs(中草药),2010,41(3):496-499.
[3]Webster I.Recent developments in pressure-sensitive adhesives for medical applications[J].Int J Adhesion&Adhesives,1997,17(1):69-73.
[4]TANG Xiu-zhen(汤秀珍),WANG Cheng-xiao(王承潇),ZHANG Hao(张皓),et al.Optimization of Guanjie Zhitonggao Patch formulation using central composite design-response surface methodology(星点设计-效应面法优化关节止痛膏贴剂处方)[J].Chinese Traditional and Herbal Drugs(中草药),2012,43(1):86-90.
[5]Nazhat S N,Parker S,Patel M P.Isoprene-styrene copolymer elastomer and tetrahydrofurfuryl methacrylate mixtures for soft prosthetic applications[J].Biomaterials,2001,22(17):2411-2416.
[6]YU Zhen-wei(俞振伟),YING Xiao-ying(应晓英),LIANG Wen-quan(梁文权),et al.Release characterization of drugs in hot-melt pressure sensitive adhesive(热熔压敏胶中药物释放性能的研究)[J].Chin Pharm(中国药学杂志),2009,44(24):1878-1882.
[7]Hayashi T,Yamazaki T,Yamaguchi Y,et al.Release kinetics of indomethacin from pressure sensitive adhesive matrices[J].J Control Release,1997,43(1-2):213-21.
[8]Morimoto Y,Kokubo T,Sugibayashi K.Diffusion of drugs in acrylic-type pressure-sensitive adhesive matrix II.Influence of interaction[J].J Control Release,1992,18(2):113-122.
[9]Kobubo T,Sugibayashi K,Yasunori M.Interaction between drugs and pressure-sensitive adhesives in transdermal therapeutic systems[J].Pharm Res,1994,11(1):104-107.
[10]Fang J Y,Wu P C,Huang Y B,et al.In vitro permeation study of capsaicin and its synthetic derivatives from ointment bases using various skin types[J].Int J Pharm,1995,126(1):119-128.
[11]Mclean R S,Sauer B B.Tapping-Mode AFM studies using phase detection for resolution of nanophases in segmented polyurethanes and other block copolymers[J].Macromolecules,1997,30(26):8314-8317.
[12]Magonov S N,Cleveland J,Elings V,et al.Tapping-mode atomic force microscopy study of the near-surface composition of a styrene-butadiene-styrene triblock copolymer film[J].Surface Sci,1997,389(1-3):201-211.
[13]Yat H K,Dodou K.Rheological studies on pressure-sensitive silicone adhesives and drug-in-adhesive layers as a means to characterize adhesive performance[J].Int J Pharm,2007,333(1-2):24-33.
[14]Gibert F X,Marin G,Derail C,et al.Rheological properties of hot melt pressure-sensitive adhesives based on styrene-isoprene copolymers.PartⅠ:A rheological model for[SIS-SI]formulations[J].J Adhesion,2003,79(8-9):825-852.
[15]Siepmann J,Siepmann F.Mathematical modeling of drug delivery[J].Int J Pharm,2008,364(2):328-343.
[16]Liu D Z,Sheu M T,Chen C H,et al.Release characteristics of lidocaine from local implant of polyanionic and polycationic hydrogels[J].J Control Release,2007,118(3):333-339.
[2]WANG Cheng-xiao(王承潇),TANG Xiu-zhen(汤秀珍),SHEN Ping-niang(沈平孃),et al.Advances in studies on hot melt pressure sensitive applied in patches of Chinese materia medica(热熔压敏胶应用于中药贴剂的研究进展)[J].Chinese Traditional and Herbal Drugs(中草药),2010,41(3):496-499.
[3]Webster I.Recent developments in pressure-sensitive adhesives for medical applications[J].Int J Adhesion&Adhesives,1997,17(1):69-73.
[4]TANG Xiu-zhen(汤秀珍),WANG Cheng-xiao(王承潇),ZHANG Hao(张皓),et al.Optimization of Guanjie Zhitonggao Patch formulation using central composite design-response surface methodology(星点设计-效应面法优化关节止痛膏贴剂处方)[J].Chinese Traditional and Herbal Drugs(中草药),2012,43(1):86-90.
[5]Nazhat S N,Parker S,Patel M P.Isoprene-styrene copolymer elastomer and tetrahydrofurfuryl methacrylate mixtures for soft prosthetic applications[J].Biomaterials,2001,22(17):2411-2416.
[6]YU Zhen-wei(俞振伟),YING Xiao-ying(应晓英),LIANG Wen-quan(梁文权),et al.Release characterization of drugs in hot-melt pressure sensitive adhesive(热熔压敏胶中药物释放性能的研究)[J].Chin Pharm(中国药学杂志),2009,44(24):1878-1882.
[7]Hayashi T,Yamazaki T,Yamaguchi Y,et al.Release kinetics of indomethacin from pressure sensitive adhesive matrices[J].J Control Release,1997,43(1-2):213-21.
[8]Morimoto Y,Kokubo T,Sugibayashi K.Diffusion of drugs in acrylic-type pressure-sensitive adhesive matrix II.Influence of interaction[J].J Control Release,1992,18(2):113-122.
[9]Kobubo T,Sugibayashi K,Yasunori M.Interaction between drugs and pressure-sensitive adhesives in transdermal therapeutic systems[J].Pharm Res,1994,11(1):104-107.
[10]Fang J Y,Wu P C,Huang Y B,et al.In vitro permeation study of capsaicin and its synthetic derivatives from ointment bases using various skin types[J].Int J Pharm,1995,126(1):119-128.
[11]Mclean R S,Sauer B B.Tapping-Mode AFM studies using phase detection for resolution of nanophases in segmented polyurethanes and other block copolymers[J].Macromolecules,1997,30(26):8314-8317.
[12]Magonov S N,Cleveland J,Elings V,et al.Tapping-mode atomic force microscopy study of the near-surface composition of a styrene-butadiene-styrene triblock copolymer film[J].Surface Sci,1997,389(1-3):201-211.
[13]Yat H K,Dodou K.Rheological studies on pressure-sensitive silicone adhesives and drug-in-adhesive layers as a means to characterize adhesive performance[J].Int J Pharm,2007,333(1-2):24-33.
[14]Gibert F X,Marin G,Derail C,et al.Rheological properties of hot melt pressure-sensitive adhesives based on styrene-isoprene copolymers.PartⅠ:A rheological model for[SIS-SI]formulations[J].J Adhesion,2003,79(8-9):825-852.
[15]Siepmann J,Siepmann F.Mathematical modeling of drug delivery[J].Int J Pharm,2008,364(2):328-343.
[16]Liu D Z,Sheu M T,Chen C H,et al.Release characteristics of lidocaine from local implant of polyanionic and polycationic hydrogels[J].J Control Release,2007,118(3):333-339.