Tina Friedenauer, Kim Buck, Maike Eberwein, Anna‐Lena Bünte, Christoph Rehbock, Stephan Barcikowski
{"title":"在液体射流通道反应器中激光破碎合成亚微米级活性药物的研究","authors":"Tina Friedenauer, Kim Buck, Maike Eberwein, Anna‐Lena Bünte, Christoph Rehbock, Stephan Barcikowski","doi":"10.1002/ppsc.202300034","DOIUrl":null,"url":null,"abstract":"Abstract One challenge in the development of new drug formulations is overcoming their low solubility in relevant aqueous media. Reducing the particle size of drug powders to a few hundred nanometers is a well‐known method that leads to an increase in solubility due to an elevated total surface area. However, state‐of‐the‐art comminution techniques like cryo‐milling suffer from degradation and contamination of the drugs, particularly when sub‐micrometer diameters are aspired that require long processing times. In this work, picosecond‐pulsed laser fragmentation in liquids (LFL) of dispersed drug particles in a liquid‐jet passage reactor is used as a wear‐free comminution technique using the hydrophobic oral model drugs naproxen, prednisolone, ketoconazole, and megestrol acetate. Particle size and morphology of the drug particles are characterized using scanning electron microscopy (SEM) and changes in particle size distributions upon irradiation are quantified using an analytical centrifuge. The findings highlight the superior fragmentation efficiency of the liquid‐jet passage reactor setup, with a 100 times higher fraction of submicrometer particles (SMP) of the drugs compared to the batch control, which enhances solubility and goes along with minimal chemical degradation (<1%), determined by attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR), high‐performance liquid chromatography (HPLC), and X‐ray diffraction (XRD). Moreover, the underlying predominantly photo‐mechanically induced laser fragmentation mechanisms of organic microparticles (MP) are discussed.","PeriodicalId":19903,"journal":{"name":"Particle & Particle Systems Characterization","volume":"31 1","pages":"0"},"PeriodicalIF":2.7000,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficient Synthesis of Submicrometer‐Sized Active Pharmaceuticals by Laser Fragmentation in a Liquid‐Jet Passage Reactor with Minimum Degradation\",\"authors\":\"Tina Friedenauer, Kim Buck, Maike Eberwein, Anna‐Lena Bünte, Christoph Rehbock, Stephan Barcikowski\",\"doi\":\"10.1002/ppsc.202300034\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract One challenge in the development of new drug formulations is overcoming their low solubility in relevant aqueous media. Reducing the particle size of drug powders to a few hundred nanometers is a well‐known method that leads to an increase in solubility due to an elevated total surface area. However, state‐of‐the‐art comminution techniques like cryo‐milling suffer from degradation and contamination of the drugs, particularly when sub‐micrometer diameters are aspired that require long processing times. In this work, picosecond‐pulsed laser fragmentation in liquids (LFL) of dispersed drug particles in a liquid‐jet passage reactor is used as a wear‐free comminution technique using the hydrophobic oral model drugs naproxen, prednisolone, ketoconazole, and megestrol acetate. Particle size and morphology of the drug particles are characterized using scanning electron microscopy (SEM) and changes in particle size distributions upon irradiation are quantified using an analytical centrifuge. The findings highlight the superior fragmentation efficiency of the liquid‐jet passage reactor setup, with a 100 times higher fraction of submicrometer particles (SMP) of the drugs compared to the batch control, which enhances solubility and goes along with minimal chemical degradation (<1%), determined by attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR), high‐performance liquid chromatography (HPLC), and X‐ray diffraction (XRD). 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Efficient Synthesis of Submicrometer‐Sized Active Pharmaceuticals by Laser Fragmentation in a Liquid‐Jet Passage Reactor with Minimum Degradation
Abstract One challenge in the development of new drug formulations is overcoming their low solubility in relevant aqueous media. Reducing the particle size of drug powders to a few hundred nanometers is a well‐known method that leads to an increase in solubility due to an elevated total surface area. However, state‐of‐the‐art comminution techniques like cryo‐milling suffer from degradation and contamination of the drugs, particularly when sub‐micrometer diameters are aspired that require long processing times. In this work, picosecond‐pulsed laser fragmentation in liquids (LFL) of dispersed drug particles in a liquid‐jet passage reactor is used as a wear‐free comminution technique using the hydrophobic oral model drugs naproxen, prednisolone, ketoconazole, and megestrol acetate. Particle size and morphology of the drug particles are characterized using scanning electron microscopy (SEM) and changes in particle size distributions upon irradiation are quantified using an analytical centrifuge. The findings highlight the superior fragmentation efficiency of the liquid‐jet passage reactor setup, with a 100 times higher fraction of submicrometer particles (SMP) of the drugs compared to the batch control, which enhances solubility and goes along with minimal chemical degradation (<1%), determined by attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR), high‐performance liquid chromatography (HPLC), and X‐ray diffraction (XRD). Moreover, the underlying predominantly photo‐mechanically induced laser fragmentation mechanisms of organic microparticles (MP) are discussed.
期刊介绍:
Particle & Particle Systems Characterization is an international, peer-reviewed, interdisciplinary journal focusing on all aspects of particle research. The journal joined the Advanced Materials family of journals in 2013. Particle has an impact factor of 4.194 (2018 Journal Impact Factor, Journal Citation Reports (Clarivate Analytics, 2019)).
Topics covered include the synthesis, characterization, and application of particles in a variety of systems and devices.
Particle covers nanotubes, fullerenes, micelles and alloy clusters, organic and inorganic materials, polymers, quantum dots, 2D materials, proteins, and other molecular biological systems.
Particle Systems include those in biomedicine, catalysis, energy-storage materials, environmental science, micro/nano-electromechanical systems, micro/nano-fluidics, molecular electronics, photonics, sensing, and others.
Characterization methods include microscopy, spectroscopy, electrochemical, diffraction, magnetic, and scattering techniques.