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纳米晶形成和包封提高非诺贝特的溶解度。

Enhancing the Solubility of Fenofibrate by Nanocrystal Formation and Encapsulation.

机构信息

School of Basic Sciences and Advanced Material Research Centre, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, 175005, India.

出版信息

AAPS PharmSciTech. 2018 Jan;19(1):284-292. doi: 10.1208/s12249-017-0840-z. Epub 2017 Jul 12.

Abstract

Development of techniques to enhance bioavailability of drugs having poor water solubility is a big challenge for pharmaceutical industry. Solubility can be enhanced by particle size reduction and encapsulation using hydrophilic polymers. Fenofibrate (FF) is a drug for regulating lipids. Multi-fold enhancement in solubility of FF has been achieved by nanocrystal formation in the present study. Nanoparticles were prepared by an evaporation-assisted solvent-antisolvent interaction (EASAI) approach. Water-soluble polymers, viz. polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC), were used to encapsulate and thus control the particle size of FF nanocrystals. Spherical particles having average particle size well below 30 nm could be prepared under optimum conditions. Almost complete release of the drug molecules from the polymer-stabilized nanocrystals within 2 h was clearly evident from the in vitro drug release studies. Infrared (FTIR) spectroscopy indicated the absence of solvent impurities and any strong interaction between the drug and stabilizers. The polymorphic form of raw-FF was retained in the nanoparticles as per the X-ray diffraction (XRD) patterns. Lower crystallinity of the nanoformulated samples compared to raw-FF was confirmed by differential scanning calorimetric (DSC) studies.

摘要

提高水溶性差的药物生物利用度的技术的发展是制药行业面临的一大挑战。可以通过减小粒径和使用亲水性聚合物包封来提高溶解度。非诺贝特(FF)是一种调节脂质的药物。本研究通过形成纳米晶体使 FF 的溶解度提高了数倍。通过蒸发辅助溶剂-反溶剂相互作用(EASAI)方法制备纳米颗粒。使用水溶性聚合物,即聚乙烯吡咯烷酮(PVP)、聚乙烯醇(PVA)和羟丙基甲基纤维素(HPMC)来包封并控制 FF 纳米晶体的粒径。在最佳条件下,可以制备平均粒径远低于 30nm 的球形颗粒。从体外药物释放研究中可以清楚地看出,聚合物稳定的纳米晶体在 2 小时内几乎可以完全释放药物分子。红外(FTIR)光谱表明药物和稳定剂之间没有溶剂杂质和任何强相互作用。根据 X 射线衍射(XRD)图谱,原料药的多晶型形式保留在纳米颗粒中。与原料药相比,纳米配方样品的结晶度较低,这一点通过差示扫描量热法(DSC)研究得到了证实。

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