影响纳米混悬剂的物理稳定性的因素及应对策略分析

Analysis and Countermeasure of the Physical Stability of Nanosuspension

摘要: 纳米混悬剂是药物制剂学中的一种重要剂型，其能够解决多数难溶性药物的溶解度问题，提高药物的生物利用度，但是其物理稳定性问题一直是其应用及产业化的瓶颈。本文总结近年来国内外具有代表性研究，进行分析、整理、归纳，为制备物理稳定的纳米混悬剂提供应对对策并进行分析。

Abstract: Nanosuspension is an important form of pharmaceutical science; it can solve most problems of drug solubility, improve the bioavailability of drugs, but its physical stability problem has been the bottleneck of application and industrialization. In this paper, the representative research was summarized, analyzed, sorted and summarized to provide and analyze countermeasures for the preparation of physical stability of the nanosuspension.

文章引用：王翠, 易方莲, 栾立标. 影响纳米混悬剂的物理稳定性的因素及应对策略分析[J]. 药物资讯, 2017, 6(2): 46-54. https://doi.org/10.12677/PI.2017.62009

参考文献

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[28]	Zhang, Y. and Cremer, P.S. (2006) Interactions between Macromolecules and Ions: The Hofmeister Series. Current Opinion in Chemical Biology, 10, 658-663.
[29]	Lee, J., Lee, S.J., Choi, J.Y., et al. (2005) Amphiphilic Amino Acid Copolymers as Stabilizers for the Preparation of Nanocrystal Dispersion. European Journal of Pharmaceutical Sciences, 24, 441-449.
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[31]	Keck, C.M. and Müller, R.H. (2006) Drug Nanocrystals of Poorly Soluble Drugs Produced by High Pressure Homogenisation. European Journal of Pharmaceutics & Biopharmaceutics, 62, 3-16.
[32]	Möschwitzer, J., Achleitner, G., Pomper, H., et al. (2004) Development of an Intravenously Injectable Chemically Stable Aqueous Omeprazole Formulation Using Nanosuspension Technology. European Journal of Pharmaceutics & Biopharmaceutics, 58, 615-619.
[33]	Yang, H., Teng, F., Wang, P., et al. (2014) Investigation of a Nanosuspension Stabilized by Soluplus® to Improve Bioavailability. International Journal of Pharmaceutics, 477, 88-95.
[34]	Ahuja, M., Dhake, A.S., Sharma, S.K., et al. (2011) Diclofenac-Loaded Eudragit S100 Nanosuspension for Ophthalmic Delivery. Journal of Microencapsulation, 28, 37-45. https://doi.org/10.3109/02652048.2010.523794
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[36]	Zakir, F., Sharma, H., Kaur, K., et al. (2011) Nanocrystallization of Poorly Water Soluble Drugs for Parenteral Administration. Journal of Biomedical Nanotechnology, 7, 127-129. https://doi.org/10.1166/jbn.2011.1234
[37]	Raula, J., Rahikkala, A., Halkola, T., et al. (2013) Coated Particle Assemblies for the Concomitant Pulmonary Administration of Budesonide and Salbutamol Sulphate. International Journal of Pharmaceutics, 441, 248-254.
[38]	Du, J., Zhou, Y., Wang, L., et al. (2016) Effect of PEGylated Chitosan as Multifunctional Stabilizer for Deacetyl Mycoepoxydience Nanosuspension Design and Stability Evaluation. Carbohydrate Polymers, 153, 471-481.
[39]	Sharma, P., Zujovic, Z.D., Bowmaker, G.A., et al. (2011) Evaluation of a Crystalline Nanosuspension: Polymorphism, Process Induced Transformation and in Vivo Studies. International Journal of Pharmaceutics, 408, 138-151.
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[41]	Pireddu, R., Sinico, C., Ennas, G., et al. (2015) Novel Nanosized Formulations of Two Diclofenac Acid Polymorphs to Improve Topical Bioavailability. European Journal of Pharmaceutical Sciences, 77, 208-215.
[42]	Wu, L., Zhang, J. and Watanabe, W. (2011) Physical and Chemical Stability of Drug Nanoparticles. Advanced Drug Delivery Reviews, 63, 456-469.
[43]	Ali, H.S., York, P. and Blagden, N. (2009) Preparation of Hydrocortisone Nanosuspension through a Bottom-Up Nanoprecipitation Technique Using Microfluidic Reactors. International Journal of Pharmaceutics, 375, 107-113.
[44]	谢向阳, 陈晨, 廖祥茹, 韩亮. 纳米混悬剂的物理稳定性研究进展[J]. 国际药学研究杂志, 2011, 1(5): 369-374.
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[46]	Yong, L., Zhao, X., Zu, Y., et al. (2015) Preparation and Characterization of Paclitaxel Nanosuspension Using Novel Emulsification Method by Combining High Speed Homogenizer and High Pressure Homogenization. International Journal of Pharmaceutics, 490, 324-333.
[47]	Lou, H., Liu, M., Qu, W., et al. (2013) The Influence of Sodium Salts (Iodide, Chloride And Sulfate) on the Formation Efficiency of Sulfamerazine Nanocrystals. Pharmaceutical Development & Technology, 19, 548-555. https://doi.org/10.3109/10837450.2013.805777
[48]	Mishra, B., Sahoo, J. and Dixit, P.K. (2016) Enhanced Bioavailability of Cinnarizine Nanosuspensions by Particle Size Engineering: Optimization and Physicochemical Investigations. Materials Science & Engineering C: Materials for Biological Applications, 63, 62-69.
[49]	George, M. and Ghosh, I. (2012) Identifying the Correlation Between Drug/Stabilizer Properties and Critical Quality Attributes (CQAs) of Nanosuspension Formulation Prepared by wet Media Milling Technology. European Journal of Pharmaceutical Sciences, 48, 142-152.
[50]	Ezhilarasi, P.N., Karthik, P., Chhanwal, N., et al. (2013) Nanoencapsulation Techniques for Food Bioactive Components: A Review. Food and Bioprocess Technology, 6, 628-647. https://doi.org/10.1007/s11947-012-0944-0
[51]	Meriskoliversidge, E. and Liversidge, G.G. (2011) Nanosizing for Oral and Parenteral Drug Delivery: A Perspective on Formulating Poorly-Water Soluble Compounds Using Wet Media Milling Technology. Advanced Drug Delivery Reviews, 63, 427-440.
[52]	Liu, D., Xu, H., Tian, B., et al. (2012) Fabrication of Carvedilol Nanosuspensions through the Anti-Solvent Precipitation-Ultrasonication Method for the Improvement of Dissolution Rate and Oral Bioavailability. AAPS PharmSciTech, 13, 295-304. https://doi.org/10.1208/s12249-011-9750-7
[53]	Hong, C., Dang, Y., Lin, G., et al. (2014) Effects of Stabilizing Agents on the Development of Myricetin Nanosuspension and Its Characterization: An in Vitro and in Vivo Evaluation. International Journal of Pharmaceutics, 477, 251- 260.
[54]	He, W., Lu, Y., Qi, J., et al. (2013) Food Proteins as Novel Nanosuspension Stabilizers for Poorly Water-Soluble Drugs. International Journal of Pharmaceutics, 441, 269-278.
[55]	Bi, Y., Liu, J., Wang, J., et al. (2015) Particle Size Control and the Interactions between Drug and Stabilizers in an Amorphous Nanosuspension System. Journal of Drug Delivery Science & Technology, 29, 167-172.
[56]	Zhang, Y., Furyk, S., Bergbreiter, D.E., et al. (2005) Specific Ion Effects on the Water Solubility of Macromolecules: PNIPAM and the Hofmeister Series. Journal of the American Chemical Society, 127, 14505-14510. https://doi.org/10.1021/ja0546424
[57]	Van, E.B., Froyen, L., Van, H.J., et al. (2008) Drying of Crystalline Drug Nanosuspensions—The Importance of Surface Hydrophobicity on Dissolution Behavior upon Redispersion. European Journal of Pharmaceutical Sciences, 35, 127-135.
[58]	Zhang, Y. and Cremer, P.S. (2006) Interactions between Macromolecules and Ions: The Hofmeister Series. Current Opinion in Chemical Biology, 10, 658-663.
[59]	Lee, J., Lee, S.J., Choi, J.Y., et al. (2005) Amphiphilic Amino Acid Copolymers as Stabilizers for the Preparation of Nanocrystal Dispersion. European Journal of Pharmaceutical Sciences, 24, 441-449.
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