阿司匹林磷脂复合物脂微球的制备及评价
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摘要
目的:制备阿司匹林磷脂复合物脂微球(ASP-PC-LM),并评价其性质。方法:采用高速剪切法制备初乳,高压均质法对初乳进行二次乳化,以离心稳定常数(Ke)及平均粒径为考察指标,单因素试验考察处方和制备工艺,并对其外观、粒径、Zeta电位及包封率进行考察。结果:ASP-PC-LM最佳处方和工艺是橄榄油与辛癸酸甘油酯(MCT)以1∶1配比(15%),油酸(0.3%)、大豆磷脂(1.2%)于70℃混合作为油相,KolliphorHS 15(2.0%)同温度下溶解于注射用水作为水相,油水两相在70℃下混合,10 000 r/min高速剪切5 min,然后在110 MPa高压均质3次,所得ASP-PC-LM外观呈圆形,平均粒径为(180.2±12.8) nm,Zeta电位为(-41.23±1.53) m V,包封率为(81.03±0.797)%,Ke为32.93±0.08。结论:最佳工艺制备ASP-PC-LM的粒径适宜、包封率高,工艺稳定性好。
Objective:To prepare aspirin phospholipid compound lipid microspheres(ASP-PC-LM and evaluate its properties.Methods:The crude emulsion was prepared by high speed shear method and secondary emulsification was performed by high pressure homogenization method.The centrifugal stability constant(Ke) and mean particle size were taken as the evaluation indexes.The single-factor test examined the formulation and preparation process;its appearance,particle size,Zeta potential and encapsulation rate were also investigated.Results:The optimized prescription process was as follows:olive oil and MCT were mixed at 1∶ 1 ratio(15 %) with oleic acid(0.3%) and soybean phospholipid(1.2%) at 70 °C as oil phase.Kolliphor HS 15(2.0%) was dissolved with water for injection at the same temperature and then the oil-water two-phase mixed under 70 ℃;high-speed shear 5 minutes at 10 000 r/min,high pressure homogenization was performed for 3 times at 110 MPa.The appearance of ASP-PC-LM presented as round,the average particle size was(180.2 ± 12.8) nm,the Zeta potential was(-41.23 ± 1.53) m V,the encapsulation rate was(81.03 ± 0.797) % and the centrifugal stability constant was(32.93 ± 0.08).Conclusion:The optimum process preparation of ASPPC-LM has the advantages of suitable particle size,high encapsulation rate and good process stability.
Objective:To prepare aspirin phospholipid compound lipid microspheres(ASP-PC-LM and evaluate its properties.Methods:The crude emulsion was prepared by high speed shear method and secondary emulsification was performed by high pressure homogenization method.The centrifugal stability constant(Ke) and mean particle size were taken as the evaluation indexes.The single-factor test examined the formulation and preparation process;its appearance,particle size,Zeta potential and encapsulation rate were also investigated.Results:The optimized prescription process was as follows:olive oil and MCT were mixed at 1∶ 1 ratio(15 %) with oleic acid(0.3%) and soybean phospholipid(1.2%) at 70 °C as oil phase.Kolliphor HS 15(2.0%) was dissolved with water for injection at the same temperature and then the oil-water two-phase mixed under 70 ℃;high-speed shear 5 minutes at 10 000 r/min,high pressure homogenization was performed for 3 times at 110 MPa.The appearance of ASP-PC-LM presented as round,the average particle size was(180.2 ± 12.8) nm,the Zeta potential was(-41.23 ± 1.53) m V,the encapsulation rate was(81.03 ± 0.797) % and the centrifugal stability constant was(32.93 ± 0.08).Conclusion:The optimum process preparation of ASPPC-LM has the advantages of suitable particle size,high encapsulation rate and good process stability.
引文
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[11]胡园,余凤莲,汪琳.前列地尔脂微球注射液的临床应用[J].内蒙古中医药,2008,14(1):59-60.
[12]荣景宏,吴凡,王芳,等.丁酸氯维地平脂微球注射液的制备及质量评价[J].沈阳药科大学学报,2015,32(7):503-509.
[13]FEI T,HUA Y,GUO F L,et al. Parenteral formulation of larotaxel lipid microsphere tackling poor solubility and chemical instability[J]. Int J Pharm,2014,460(3):212-219.
[14]JINGLONG M A,HUAN T,JUAN W,et al. A highly stable norcantharidin loaded lipid microspheres:preparation,biodistribution and targeting evaluation[J]. Int J Pharm,2014,473(6):475-484.
[15]章秀丽,马月琴,李刚.脂微球载药系统的研究进展[J].药学实践杂志,2014,32(6):409-411.
[2]CHARLES H H,JAMES E D. Aspirin in the treatment and prevention of cardiovascular disease:past and current perspectives and future directions[J]. Am J Med,2013,126(5):373-378.
[3]JI M A,ZHONGLIN C,HONGl IANG W,et al. The antitumor effect of aspirin:what we know and what we expect[J]. Biomed. Pharmacother,2017,95(7):656-661.
[4]WANG X W,JINGJUN L U,MAGOMED KHAIDAKOV,et al. Asiprin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription[J]. Toxicol App Pharmacol,2012,259(3):246-354.
[5]涂琳,张彦燕,杨钰萍,等.阿司匹林对大鼠急性心肌梗死后诱发实验性心肌纤维化的防治作用[J].中国医院药学杂志,2012,32(11):827-831.
[6]陶振钢,袁颖,顾俭勇,等.阿司匹林对博莱霉素致大鼠肺间质纤维化的抑制作用及其机制[J].复旦学报(医学版),2013,40(4):395-399.
[7]LUO L F,WANG X Z,CHEN Q Y,et al. A parenteral docetaxel-loaded lipid microsphere with decreased 7-epidocetaxel conversion in vitro and in vivo[J]. Eur J Pharm Sci,2017,109(8):638-649.
[8]黄芳,罗晶,赵国巍,等.星点设计-效应面法优化丹参酮ⅡA脂微球处方工艺研究及质量评价[J].中国医院药学杂志,2016,36(5):346-351.
[9]黄惠锋,姚芳,白雪.前列腺素E1冻干脂微球在比格犬体内的药动学[J].山东大学学报医学版,2015,53(12):38-42.
[10]傅军霞,姚芳,胡爱珍,等.前列地尔冻干脂微球的制备及其体内外评价[J].中国药学杂志,2015,50(19):1704-1708.
[11]胡园,余凤莲,汪琳.前列地尔脂微球注射液的临床应用[J].内蒙古中医药,2008,14(1):59-60.
[12]荣景宏,吴凡,王芳,等.丁酸氯维地平脂微球注射液的制备及质量评价[J].沈阳药科大学学报,2015,32(7):503-509.
[13]FEI T,HUA Y,GUO F L,et al. Parenteral formulation of larotaxel lipid microsphere tackling poor solubility and chemical instability[J]. Int J Pharm,2014,460(3):212-219.
[14]JINGLONG M A,HUAN T,JUAN W,et al. A highly stable norcantharidin loaded lipid microspheres:preparation,biodistribution and targeting evaluation[J]. Int J Pharm,2014,473(6):475-484.
[15]章秀丽,马月琴,李刚.脂微球载药系统的研究进展[J].药学实践杂志,2014,32(6):409-411.