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熔融超声结晶对乙酰氨基酚、吲哚美辛和甲芬那酸的药剂学性质的影响,通过动态激光散射进行表征及其对溶解度的影响。

Effect of melt sonocrystallization on pharmacotechnical properties of paracetamol, indomethacin and mefenamic acid characterized by dynamic laser scattering and its impact on solubility.

机构信息

Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh, India.

出版信息

Drug Dev Ind Pharm. 2013 May;39(5):687-95. doi: 10.3109/03639045.2012.687743. Epub 2012 May 27.

Abstract

The purpose of the research was to employ a novel particle engineering technique-melt sonocrystallization (MSC) for some nonsteroidal anti-inflammatory drugs for development of more soluble forms of the drugs without the use of excipients. The original forms of Paracetamol (OFPCM), Indomethacin (OFIMC) and Mefenamic acid (OFMA) were subjected to MSC to improve physicochemical properties. MSC forms of PCM, IMC and MA were subjected to dynamic laser scattering for particle size analysis to quantize mean particle size, specific surface area, interquartile coefficient of skewness, kurtosis and span. Rheological and solubility analysis, X-ray powder diffraction and scanning electron microscopy were conducted for validating the effect of MSC on powder particles. On melt sonocrystallized form of drug powders exhibited improved micromeritic properties, the mean particle size was reduced while the specific surface area increased effectively. Frequency distribution curves showed reduction in asymmetry and skewness that was confirmed by interquartile coefficient of skewness values. Equilibrium solubility of MSC form of PCM, IMC and MA was higher than the original forms. Similarly the intrinsic dissolution rate was approximately 1.5 times higher in comparison to original form of drugs. X-ray powder diffraction shows decreased relative intensities of peaks of MSC forms due to reduction in the crystallinity that was confirmed by visualization of MSC particles by scanning electron microscopy. Conclusively, MSC is a promising cost-effective technique that may afford powder with improved flow and formulative properties as well as improved solubility and dissolution.

摘要

本研究旨在采用一种新颖的粒子工程技术——熔融超声结晶(MSC),开发一些非甾体抗炎药的更易溶形式,而不使用赋形剂。对扑热息痛(OFPCM)、吲哚美辛(OFIMC)和甲芬那酸(OFMA)的原始形式进行 MSC,以改善物理化学性质。对 PCM、IMC 和 MA 的 MSC 形式进行动态激光散射,进行粒径分析,以量化平均粒径、比表面积、四分位偏度系数、峰度和跨度。进行流变学和溶解度分析、X 射线粉末衍射和扫描电子显微镜,以验证 MSC 对粉末颗粒的影响。在熔融超声结晶药物粉末形式上表现出改善的微粉特性,平均粒径减小,而比表面积有效增加。频率分布曲线显示不对称性和偏度降低,通过偏度四分位系数值确认。MSC 形式的 PCM、IMC 和 MA 的平衡溶解度高于原始形式。同样,与药物的原始形式相比,固有溶解速率约提高 1.5 倍。X 射线粉末衍射显示由于结晶度降低,MSC 形式的峰相对强度降低,这通过扫描电子显微镜观察 MSC 颗粒得到证实。总之,MSC 是一种很有前途的具有成本效益的技术,可以提供改善流动性和配方性能以及提高溶解度和溶解的粉末。

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