Norfloxacin-CO2 crystal formed under supercritical CO2 and enhanced Norfloxacin dissolution properties

IF 3.4 3区工程技术 Q2 CHEMISTRY, PHYSICAL

Journal of Supercritical Fluids Pub Date : 2023-07-01 DOI:10.1016/j.supflu.2023.105919

Yingquan Hao , Seika Akiyama , YingChieh Hung , Sergei G. Kazarian , Yusuke Shimoyama

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引用次数: 0

Abstract

A molecular crystal of Norfloxacin coupled with CO₂, was produced after the supercritical CO₂ treatment of Norfloxacin form B. The effects of pressure and temperature on Norfloxacin-CO₂ crystal formation are studied semi-quantitatively using on powder XRD and TGA. The higher pressure and temperature conditions result in the formation of more Norfloxacin-CO₂ crystals for a limited time. Based on these results, pure Norfloxacin-CO₂ crystals are fabricated. Through further studies, we found out that CO₂ is fixed in Norfloxacin-CO₂ crystal through the formation of a paired carbamic acid structure with two piperazine groups from two adjacent Norfloxacin molecules. The fixed CO₂ can be released during dissolution, improving the equilibrium solubility of Norfloxacin from 0.28 mg g⁻¹ water to 0.64 mg g⁻¹ water at 25 ºC. Since no toxic organic solvent used, this research offers a new pathway for greener and safer enhancement for the dissolution properties of poorly soluble APIs.

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在超临界CO2作用下形成诺氟沙星-CO2晶体，提高了诺氟沙星的溶出性能

通过超临界CO2处理诺氟沙星B型，制备了诺氟沙星与CO2偶联的分子晶体。利用粉末XRD和TGA半定量研究了压力和温度对诺氟沙星-CO2晶体形成的影响。较高的压力和温度条件导致在有限的时间内形成更多的Norfloxacin-CO2晶体。基于这些结果，制备了纯的Norfloxacin-CO2晶体。通过进一步的研究，我们发现CO2通过由两个相邻的诺氟沙星分子形成具有两个哌嗪基团的配对氨基甲酸结构而固定在诺氟沙星-CO2晶体中。溶解过程中可以释放固定的CO2，将诺氟沙星在25ºC下的平衡溶解度从0.28 mg g−1水提高到0.64 mg g−2水。由于不使用有毒有机溶剂，本研究为提高难溶性原料药的溶解性能提供了一条更绿色、更安全的新途径。

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来源期刊

Journal of Supercritical Fluids 工程技术-工程：化工

CiteScore

7.60

自引率

10.30%

发文量

236

审稿时长

56 days

期刊介绍： The Journal of Supercritical Fluids is an international journal devoted to the fundamental and applied aspects of supercritical fluids and processes. Its aim is to provide a focused platform for academic and industrial researchers to report their findings and to have ready access to the advances in this rapidly growing field. Its coverage is multidisciplinary and includes both basic and applied topics. Thermodynamics and phase equilibria, reaction kinetics and rate processes, thermal and transport properties, and all topics related to processing such as separations (extraction, fractionation, purification, chromatography) nucleation and impregnation are within the scope. Accounts of specific engineering applications such as those encountered in food, fuel, natural products, minerals, pharmaceuticals and polymer industries are included. Topics related to high pressure equipment design, analytical techniques, sensors, and process control methodologies are also within the scope of the journal.