负极性驻极体静电场对5-氟尿嘧啶贴剂体外释放规律的影响
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摘要
目的研究5-氟尿嘧啶(5-fluorouracil,5-FU)贴剂的处方优化工艺及负极性驻极体静电场对5-FU体外释放规律的影响。方法采用常温电晕充电技术制备-1 000V负极性驻极体和-2 000V负极性驻极体,以压敏胶Eudragit E100为基质、柠檬酸三丁酯为增塑剂、水溶性氮酮为化学促渗剂制备负极性驻极体5-FU贴剂。单因素考察压敏胶Eudragit E100、增塑剂、水溶性氮酮和负极性驻极体对5-FU贴剂相关参数的影响,通过正交设计试验筛选5-FU贴剂的最优处方。利用改良的Franz扩散池和高效液相色谱仪研究负极性驻极体静电场对5-FU体外释放规律的影响。结果 (1)0.25g Eudragit E100、增塑剂和Eudragit E100的质量比为55∶100、水溶性氮酮的质量分数为3%组合时为5-FU贴剂的最优处方。(2)-1 000V驻极体和-2 000V驻极体均促进了5-FU的体外释放,且电压越高促进作用越强。(3)与单用3%水溶性氮酮相比,负极性驻极体联合质量分数为3%的水溶性氮酮进一步提高了5-FU的体外释放量(P<0.05)。结论负极性驻极体与水溶性氮酮均能降低5-FU贴剂的持黏力,促进5-FU的体外释放,两者联合使用时促进作用更为显著。
Objective To explore the effects of prescription optimization of 5-fluorouracil(5-FU)patch and electrostatic field of the negative polarity electret on the in vitro release behavior of 5-FU from the 5-FU patch.Methods The corona charging technology at ambient temperature was applied for preparation of-1 000 V and-2 000 V negative polarity electrets.The negative polarity electret 5-FU patch was prepared by using Eudragit E100 as pressuresensitive adhesive(PSA),tributyl citrate as plasticizer,and water-soluble azone as chemical permeation enhancer.We used the single factor method to investigate the influences of PSA,plasticizer,water-soluble azone and negative polarity electret on the relevant parameters of the 5-FU patch.The optimal prescription was screened by orthogonal design test.We also studied the influence of negative polarity electret on the in vitro release behavior of 5-FU from the 5-FU patch by using modified Franz diffusion cell and high-performance liquid chromatography.Results(1)The optimal prescription was fitting when the mass of Eudragit E100 was 0.25 g,the mass ratio of plasticizer to Eudragit E100 was 55∶100and the mass fraction of water-soluble azone was 3%.(2)Both the-1 000Vand-2 000 Vnegative polarity electrets used in this study promoted the in vitro release of 5-FU from the 5-FU patch;and the promoting effect was proportional to the surface potential of the electret.(3)Compared with the single use of 3% water-soluble azone,negative polarity electret combined with 3% water-soluble azone significantly increased the in vitro release of 5-FU from the 5-FU patch(P<0.05).Conclusion Negative polarity electret and water-soluble azone can reduce the holding capacity of the 5-FU patch and promote the in vitro release of 5-FU from the 5-FU patch,and the promoting effect is more significant in the combination of them.
Objective To explore the effects of prescription optimization of 5-fluorouracil(5-FU)patch and electrostatic field of the negative polarity electret on the in vitro release behavior of 5-FU from the 5-FU patch.Methods The corona charging technology at ambient temperature was applied for preparation of-1 000 V and-2 000 V negative polarity electrets.The negative polarity electret 5-FU patch was prepared by using Eudragit E100 as pressuresensitive adhesive(PSA),tributyl citrate as plasticizer,and water-soluble azone as chemical permeation enhancer.We used the single factor method to investigate the influences of PSA,plasticizer,water-soluble azone and negative polarity electret on the relevant parameters of the 5-FU patch.The optimal prescription was screened by orthogonal design test.We also studied the influence of negative polarity electret on the in vitro release behavior of 5-FU from the 5-FU patch by using modified Franz diffusion cell and high-performance liquid chromatography.Results(1)The optimal prescription was fitting when the mass of Eudragit E100 was 0.25 g,the mass ratio of plasticizer to Eudragit E100 was 55∶100and the mass fraction of water-soluble azone was 3%.(2)Both the-1 000Vand-2 000 Vnegative polarity electrets used in this study promoted the in vitro release of 5-FU from the 5-FU patch;and the promoting effect was proportional to the surface potential of the electret.(3)Compared with the single use of 3% water-soluble azone,negative polarity electret combined with 3% water-soluble azone significantly increased the in vitro release of 5-FU from the 5-FU patch(P<0.05).Conclusion Negative polarity electret and water-soluble azone can reduce the holding capacity of the 5-FU patch and promote the in vitro release of 5-FU from the 5-FU patch,and the promoting effect is more significant in the combination of them.
引文
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[14]苑旺,梁媛媛,崔黎丽,江键,王美玲,石岩.正极性聚丙烯驻极体对糖尿病大鼠皮肤结构的影响[J].中国医学物理学杂志,2015,32:835-840.
[15]SAVOJI H,MEHDIZADEH A,RAMAZANI SAADAT ABADI A.Transdermal nitroglycerin delivery using acrylic matrices:design,formulation,and in vitro characterization[J].ISRN Pharm,2014,2014:493245.
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[17]董岸杰,张睿,张建华,邓联东.共聚物压敏胶的链段结构对其力学性能和药物释放的调控[J].天津大学学报,2012,45:1013-1019.
[18]NARASIMHA SATHYANARAYANA MURTHY N S,BOGUDA V A,PAYASADA K.Electret enhances transdermal drug permeation[J].Biol Pharm bull,2008,31:99-102.
[19]CUI L L,LIANG L L,MA L,GUO X,LIU H Y,JIANG J.The combinational effect of PP electret and monolein on transdermal delivery of cyclosprorin Ain vitro[J].J Electrost,2013,71:224-227.
[20]CUI L L,LIU H Y,MA L,LIANG Y Y,JIANG J.Enhanced transdermal delivery of cyclosporin a by electret and ethyl oleate[J].IEEE Trans Dielectr Electr Insul,2012,19:1191-1194.
[21]邹浪,李晓芳,邓红,曹森.氟尿嘧啶的理化性质及透皮促渗剂对氟尿嘧啶经皮渗透的研究[J].江西中医学院学报,2013(6):63-66.
[2]POETSCHKE J,GAUGLITZ G G.Current options for the treatment of pathological scarring[J].J Dtsch Dermatol Ges,2016,14:467-477.
[3]武晓莉,刘伟,曹谊林.低浓度5-氟尿嘧啶抑制血管增生在瘢痕疙瘩综合治疗中的作用初探[J].中华整形外科杂志,2007,22:44-46.
[4]KHAN M A,BASHIR M M,KHAN F A.Intralesional triamcinolone alone and in combination with 5-fluorouracil for the treatment of Keloid and Hypertrophic scars[J].J Pak Med Assoc,2014,64:1003-1007.
[5]HUANG L,CAI Y J,LUNG I,LEUNG B C,BURD A.A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro[J/OL].J Plast Reconstr Aesthet Surg,2013,66:e251-e259.doi:10.1016/j.bjps.2013.06.004.
[6]JONES C D,GUIOT L,SAMY M,GORMAN M,TEHRANI H.The use of chemotherapeutics for the treatment of keloid scars[J].Dermatol reports,2015,7:5880.
[7]GAUGLITZ G G.Management of keloids and hypertrophic scars:current and emerging options[J].Clin Cosmet Investig Dermatol,2013,6:103-114.
[8]HUSSAIN A,HAQUE W,SINGH S K,AHMED F J.Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert:partⅡ[J].Drug deliv,2015,23:1242-1253.
[9]PRAUSNITZ M R,LANGER R.Transdermal drug delivery[J].Nat Biotechnol,2008,26:1261-1268.
[10]夏钟福.驻极体[M].北京:科学出版社,2001:1-2.
[11]孔玉秀,程亮,肖永恒,王冬,江键,崔黎丽.驻极体利多卡因贴剂的透皮促渗作用[J].第二军医大学学报,2009,30:469-472.KONG Y X,CHENG L,XIAO Y H,WANG D,JIANG J,CUI L L.Enhancing effects of electret on transdermal delivery of lidocaine patches in vitro[J].Acad J Sec Mil Med Univ,2009,30:469-472.
[12]侯雪梅,崔黎丽,江键,李国栋,梁媛媛,宋茂海,等.驻极体与化学促渗剂对美洛昔康促渗作用的比较研究[J].第二军医大学学报,2007,28:709-713.HOU X M,CUI L L,JIANG J,LI G D,LIANG Y Y,SONG M H,et al.Comparison of electret and chemical enhancers in enhancing transdermal delivery of meloxicam[J].Acad J Sec Mil Med Univ,2007,28:709-713.
[13]刘鸿越,江键,马琳,梁媛媛,董法杰,崔黎丽.驻极体及联用氮酮对环孢菌素A的体外透皮促渗作用[J].药学实践杂志,2012,30:440-442,466.
[14]苑旺,梁媛媛,崔黎丽,江键,王美玲,石岩.正极性聚丙烯驻极体对糖尿病大鼠皮肤结构的影响[J].中国医学物理学杂志,2015,32:835-840.
[15]SAVOJI H,MEHDIZADEH A,RAMAZANI SAADAT ABADI A.Transdermal nitroglycerin delivery using acrylic matrices:design,formulation,and in vitro characterization[J].ISRN Pharm,2014,2014:493245.
[16]周卫新,袁永健,石俭莉,虞小松.压敏胶黏剂的研究进展[J].化工新型材料,2009,37:37-39,43.
[17]董岸杰,张睿,张建华,邓联东.共聚物压敏胶的链段结构对其力学性能和药物释放的调控[J].天津大学学报,2012,45:1013-1019.
[18]NARASIMHA SATHYANARAYANA MURTHY N S,BOGUDA V A,PAYASADA K.Electret enhances transdermal drug permeation[J].Biol Pharm bull,2008,31:99-102.
[19]CUI L L,LIANG L L,MA L,GUO X,LIU H Y,JIANG J.The combinational effect of PP electret and monolein on transdermal delivery of cyclosprorin Ain vitro[J].J Electrost,2013,71:224-227.
[20]CUI L L,LIU H Y,MA L,LIANG Y Y,JIANG J.Enhanced transdermal delivery of cyclosporin a by electret and ethyl oleate[J].IEEE Trans Dielectr Electr Insul,2012,19:1191-1194.
[21]邹浪,李晓芳,邓红,曹森.氟尿嘧啶的理化性质及透皮促渗剂对氟尿嘧啶经皮渗透的研究[J].江西中医学院学报,2013(6):63-66.