扫码关注我们

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

扫描电子显微镜在缓释微球制剂表征中的应用进展

陈超 樊海丽 蔡志威 张传杰

陈超, 樊海丽, 蔡志威, 张传杰. 扫描电子显微镜在缓释微球制剂表征中的应用进展[J]. 分析测试技术与仪器, 2022, 28(2): 132-138. doi: 10.16495/j.1006-3757.2022.02.004
引用本文: 陈超, 樊海丽, 蔡志威, 张传杰. 扫描电子显微镜在缓释微球制剂表征中的应用进展[J]. 分析测试技术与仪器, 2022, 28(2): 132-138. doi: 10.16495/j.1006-3757.2022.02.004
CHEN Chao, FAN Hai-li, CAI Zhi-wei, ZHANG Chuan-jie. Progress in Characterization of Controlled Release Microspheres Using Scanning Electron Microscope[J]. Analysis and Testing Technology and Instruments, 2022, 28(2): 132-138. doi: 10.16495/j.1006-3757.2022.02.004
Citation: CHEN Chao, FAN Hai-li, CAI Zhi-wei, ZHANG Chuan-jie. Progress in Characterization of Controlled Release Microspheres Using Scanning Electron Microscope[J]. Analysis and Testing Technology and Instruments, 2022, 28(2): 132-138. doi: 10.16495/j.1006-3757.2022.02.004

扫描电子显微镜在缓释微球制剂表征中的应用进展

doi: 10.16495/j.1006-3757.2022.02.004
基金项目: 

2021年度国家药品标准制修订研究课题 2021Y05

详细信息
    作者简介:

    陈超(1977-),男,高级工程师,主要从事药物分析工作,Tel: (0571)87180328,E-mail: chenchao@zjyj.org.cn

    通讯作者:

    张传杰(1988-),男,工学硕士,主要从事药物仪器分析工作,Tel: (021)52236526,E-mail: jack.zhang@phenom-china.com

  • 中图分类号: TN16;R284.1

Progress in Characterization of Controlled Release Microspheres Using Scanning Electron Microscope

Funds: 

2021 National Drug Standard Formulation and Revision Research Project 2021Y05

  • 摘要: 综述扫描电子显微镜在缓释微球制剂表征中的重要应用. 采用扫描电子显微镜法对缓控释微球制剂进行表征, 采用自动颗粒粒形、粒径图像识别法对微球进行统计学分析, 对扫描电子显微镜在控释微球制剂研发过程中的4个广泛应用场景进行论证和总结. 缓控释微球制剂学是高度依赖结构学的制剂类型, 其性能和治疗功效很大程度上取决于微球的微观特性, 如结构、孔径等. 微球颗粒的尺寸及粒度分布、形状对药物释放起决定性作用. 扫描电子显微镜具有所见即所得的优势, 可以很直观的对微球颗粒的粒径、粒形以及表面粗糙情况进行快速评估. 由于微球制剂高药物载量的特点, 其批间一致性尤为重要, 科学的图像识别分析方法对批间一致性的评估具有重要应用价值. 结果表明, 扫描电子显微镜在微球的研发与生产控制中具有广泛的应用价值, 为此类型制剂的研发提供了先进的表征工具.
  • 图  1  不同粒度微球的SEM图像[31]

    Figure  1.  SEM images of microspheres showing different particle sizes[31]

    图  2  不同粒度微球的SEM图像(标尺尺寸100 μm)[29]

    Figure  2.  SEM images of microspheres with different particle sizes (scale bar 100 μm)[29]

    图  3  SEM图像分析结果:微球粒度分布分析

    Figure  3.  SEM images analysis results: microsphere size distribution analysis

    图  4  微球孔结构SEM表征[39]

    Figure  4.  SEM characterization of microsphere pore structure[39]

    图  5  多孔微球(a)及包覆后的核壳微球(b)

    Figure  5.  Porous microspheres (a) and coated core-shell microspheres (b)

    图  6  不同工艺条件下的微球断面表征

    (a)内部孔径较大,疏松,(b) 内部孔径较小,较为致密

    Figure  6.  Characterization of cross section of microspheres under different process conditions

    (a) large inner pore size and loose structure, (b) small inner pore size and dense structure

  • [1] Spizzirri U G. Functional polymers for controlled drug release[J]. Pharmaceutics, 2020, 12(2): 135. doi: 10.3390/pharmaceutics12020135
    [2] Mishra M. Handbook of encapsulation and controlled release[M]. Boca Raton: CRC Press, 2015.
    [3] Feng S S, Chien C E. Chemotherapeutic engineering[M]. 2014.
    [4] 桑国卫, 樊代明, 杨胜利, 张伯礼. 创新药物研发方法及策略[M]. 北京: 高等教育出版社, 2015.
    [5] Alavi M, Webster T J. Recent progress and challenges for polymeric microsphere compared to nanosphere drug release systems: is there a real difference?[J]. Bioorganic & Medicinal Chemistry, 2021, 33: 116028.
    [6] Duraikkannu S L, Castro-Muñoz R, Figoli A. A review on phase-inversion technique-based polymer microsphere fabrication[J]. Colloid and Interface Science Communications, 2021, 40: 100329. doi: 10.1016/j.colcom.2020.100329
    [7] Kim K K, Pack D W. Microspheres for drug delivery[M]//Ferrari M, Lee A P, Lee L J. BioMEMS and biomedical nanotechnology: Volume I Biological and biomedical nanotechnology. Boston, MA: Springer US, 2006: 19-50.
    [8] Wang Y, Burgess D J. Microsphere technologies[M]//Longacting injections and implants. Boston, MA: Springer US, 2011: 167-194.
    [9] Rane A, Thomas S, Kalarikkal N. Microscopy applied to materials sciences and life sciences[M]. Boca Raton: CRC Press, 2018.
    [10] Bunjes H, Kuntsche J. Light and electron microscopy[M]. 2016: 491-522.
    [11] Newman A, Wenslow R. Solid-state characterization techniques[M]. 2018.
    [12] Shur J, Price R. Advanced microscopy techniques to assess solid-state properties of inhalation medicines[J]. Advanced Drug Delivery Reviews, 2012, 64(4): 369-382. doi: 10.1016/j.addr.2011.11.005
    [13] Arsiccio A, Barresi A A, Pisano R. Prediction of ice crystal size distribution after freezing of pharmaceutical solutions[J]. Crystal Growth & Design, 2017, 17(9): 4573-4581.
    [14] Oddone I, Barresi A A, Pisano R. Influence of controlled ice nucleation on the freeze-drying of pharmaceutical products: the secondary drying step[J]. International Journal of Pharmaceutics, 2017, 524(1-2): 134-140. doi: 10.1016/j.ijpharm.2017.03.077
    [15] Khadhraoui B, Turk M, Fabiano-Tixier A S, Petitcolas E, Robinet P, Imbert R, Maâtaoui M E, Chemat F. Histo-cytochemistry and scanning electron microscopy for studying spatial and temporal extraction of metabolites induced by ultrasound. Towards chain detexturation mechanism[J]. Ultrasonics Sonochemistry, 2018, 42: 482-492. doi: 10.1016/j.ultsonch.2017.11.029
    [16] Balasubramani K, Sivarajasekar N, Naushad M. Effective adsorption of antidiabetic pharmaceutical (metformin) from aqueous medium using graphene oxide nanoparticles: equilibrium and statistical modelling[J]. Journal of Molecular Liquids, 2020, 301: 12426.
    [17] Khan B M, Qiu H M, Xu S Y, Liu Y, Cheong K L. Physicochemical characterization and antioxidant activity of sulphated polysaccharides derived from porphyra haitanensis[J]. International Journal of Biological Macromolecules, 2020, 145: 1155-1161. doi: 10.1016/j.ijbiomac.2019.10.040
    [18] Khan M S I, Oh S W, Kim Y J. Power of scanning electron microscopy and energy dispersive X-ray analysis in rapid microbial detection and identification at the single cell level[J]. Scientific Reports, 2020, 10: 2368. doi: 10.1038/s41598-020-59448-8
    [19] Adewoye S O, Adenigba V O, Adewoye A O, Adagunodo T A. Bioremediation of heavy metals from pharmaceutical industry sewages using bimetallic nanoparticles of eichorniacrassipes[J]. IOP Conference Series: Earth and Environmental Science, 2021, 655(1): 012021. doi: 10.1088/1755-1315/655/1/012021
    [20] Tacke S, Lucas F, Woodward J D, Gross H, Wepf R. High-resolution cryo-scanning electron microscopy of macromolecular complexes[M]//Biological field emission scanning electron microscopy. Chichester, UK: John Wiley & Sons, Ltd, 2019: 265-297.
    [21] Muralidharan P, Acosta M F, Hayes D, Black S M, Mansour H M. Solid-state physicochemical characterization and microscopy of particles in dry powder inhalers[J]. Inhalation, 2016, 10(2): 20-26.
    [22] Vetráková L', Neděla V, Runštuk J, Heger D. The morphology of ice and liquid brine in an environmental scanning electron microscope: a study of the freezing methods[J]. The Cryosphere, 2019, 13(9): 2385-2405. doi: 10.5194/tc-13-2385-2019
    [23] Zhao A Q, Yu L, Yang M, Wang C J, Wang M M, Bai X. Effects of the combination of freeze-thawing and enzymatic hydrolysis on the microstructure and physicochemical properties of porous corn starch[J]. Food Hydrocolloids, 2018, 83: 465-472. doi: 10.1016/j.foodhyd.2018.04.041
    [24] Mady O. Span 60 as a microsphere matrix: preparation and in vitro characterization of novel ibuprofen-span 60 microspheres[J]. Journal of Surfactants and Detergents, 2017, 20(1): 219-232. doi: 10.1007/s11743-016-1907-7
    [25] 李想, 孙考祥, 李又欣. 长效微球制剂产业化研究进展[J]. 中国药学杂志, 2019, 54(21): 1729-1733. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYX201921002.htm

    LI Xiang, SUN Kao-xiang, LI You-xin. Progress in the industrialization of sustained-release microsphere[J]. Chinese Pharmaceutical Journal, 2019, 54(21): 1729-1733. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYX201921002.htm
    [26] Liu Z, Ye W L, Zheng J C, Wang Q D, Ma G W, Liu H Y, Wang X M. Hierarchically electrospraying a PLGA@chitosan sphere-in-sphere composite microsphere for multi-drug-controlled release[J]. Regenerative Biomaterials, 2020, 7(4): 381-390. doi: 10.1093/rb/rbaa009
    [27] Yao S L, Liu H Y, Yu S K, Li YY, Wang X M, Wang L N. Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior[J]. Regenerative Biomaterials, 2016, 3(5): 309-317. doi: 10.1093/rb/rbw033
    [28] Zhai J Q, Wang Y, Zhou X P, Ma Y, Guan S X. Long-term sustained release poly(lactic-co-glycolic acid) microspheres ofasenapine maleate with improved bioavailability for chronic neuropsychiatric diseases[J]. Drug Delivery, 2020, 27(1): 1283-1291. doi: 10.1080/10717544.2020.1815896
    [29] Berkland C, Kim K, Pack D W. PLG microsphere size controls drug release rate through several competing factors[J]. Pharmaceutical Research, 2003, 20(7): 1055-1062. doi: 10.1023/A:1024466407849
    [30] Uyen N T T, Hamid Z A A, Tram N X T, Ahmad N. Fabrication of alginate microspheres for drug delivery: a review[J]. International Journal of Biological Macromolecules, 2020, 153: 1035-1046. doi: 10.1016/j.ijbiomac.2019.10.233
    [31] Klose D, Siepmann F, Elkharraz K, Krenzlin S, Siepmann J. How porosity and size affect the drug release mechanisms from PLGA-based microparticles[J]. International Journal of Pharmaceutics, 2006, 314(2): 198-206. doi: 10.1016/j.ijpharm.2005.07.031
    [32] Wang T, Rodriguez-Uribe A, Misra M, Mohanty A K. Sustainable carbonaceous biofiller from miscanthus: size reduction, characterization, and potential bio-composites applications[J]. BioResources, 2018, 13(2): 3720-3739.
    [33] Gonzalez deGortari M, Rodriguez-Uribe A, Misra M, Mohanty A K. Insights on the structure-performance relationship of polyphthalamide (PPA) composites reinforced with high-temperature produced biocarbon[J]. RSC Advances, 2020, 10(45): 26917-26927. doi: 10.1039/D0RA03629C
    [34] Xu J H, Bai Y J, Li X H, Wei Z P, Sun L, Yu H D, Xu H. Porous core/dense shell PLA microspheres embedded with high drug loading of bupivacaine crystals for injectable prolonged release[J]. AAPS PharmSciTech, 2021, 22(1): 27. doi: 10.1208/s12249-020-01878-8
    [35] Obeidat W M, Price J C. Evaluation of enteric matrix microspheres prepared by emulsion-solvent evaporation using scanning electron microscopy[J]. Journal of Microencapsulation, 2004, 21(1): 47-57. doi: 10.1080/02652040310001619983
    [36] Zhang C Y, Wang A P, Wang H Y, Yan M C, Liang R C, He X T, Fu F H, Mu H J, Sun K X. Entecavir-loaded poly (lactic-co-glycolic acid) microspheres for long-term therapy of chronic hepatitis-B: preparation and in vitro and in vivo evaluation[J]. International Journal of Pharmaceutics, 2019, 560: 27-34. doi: 10.1016/j.ijpharm.2019.01.052
    [37] Peng T T, Zhang X J, Huang Y, Zhao Z Y, Liao Q Y, Xu J, Huang Z W, Zhang J W, Wu C Y, Pan X, Wu C B. Nanoporous mannitol carrier prepared by non-organic solvent spray drying technique to enhance the aerosolization performance for dry powder inhalation[J]. Scientific Reports, 2017, 7: 46517. doi: 10.1038/srep46517
    [38] Fan J B, Huang C, Jiang L, Wang S T. Nanoporous microspheres: from controllable synthesis to healthcare applications[J]. Journal of Materials Chemistry B, 2013, 1(17): 2222-2235. doi: 10.1039/c3tb00021d
    [39] Kim H K, Chung H J, Park T G. Biodegradable polymeric microspheres with "open/closed" pores for sustained release of human growth hormone[J]. Journal of Controlled Release, 2006, 112(2): 167-174. doi: 10.1016/j.jconrel.2006.02.004
    [40] Jiang P F, Jacobs K M, Ohr M P, Swindle-Reilly K E. Chitosan-polycaprolactone core-shell microparticles for sustained delivery of bevacizumab[J]. Molecular Pharmaceutics, 2020, 17(7): 2570-2584. doi: 10.1021/acs.molpharmaceut.0c00260
    [41] van derKooij R S, Steendam R, Frijlink H W, Hinrichs W L J. An overview of the production methods for core-shell microspheres for parenteral controlled drug delivery[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2022, 170: 24-42. doi: 10.1016/j.ejpb.2021.11.007
    [42] Ranganath S H, Kee I, Krantz W B, Chow P K H, Wang C H. Hydrogel matrix entrapping PLGA-paclitaxel microspheres: drug delivery with near zero-order release and implantability advantages for malignant brain tumour chemotherapy[J]. Pharmaceutical Research, 2009, 26(9): 2101-2114. doi: 10.1007/s11095-009-9922-2
    [43] Du Y H, Mo L J, Wang X D, Wang H X, Ge X H, Qiu T. Preparation of mint oil microcapsules by microfluidics with high efficiency and controllability in release properties[J]. Microfluidics and Nanofluidics, 2020, 24(6): 1-11.
  • 加载中
图(6)
计量
  • 文章访问数:  52
  • HTML全文浏览量:  19
  • PDF下载量:  19
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-05-23
  • 修回日期:  2022-06-01
  • 网络出版日期:  2022-07-07
  • 刊出日期:  2022-06-30

目录

    /

    返回文章
    返回