Crofton Andrew R, Hudson Samuel M, Howard Kristy, Pender Tyler, Abdelgawad Abdelrahman, Wolski Daniel, Kirsch Wolff M
Department of Anatomy, School of Medicine, Loma Linda University, 11234 Anderson St., Medical Center A537, Loma Linda, CA 92350, United States; Neurosurgery Center for Research, Training, and Education, School of Medicine, Loma Linda University, 11234 Anderson St., Medical Center A537, Loma Linda, CA 92350, United States.
College of Textiles, North Carolina State University, 2401 Research Dr., Raleigh, NC 27695, United States.
Carbohydr Polym. 2016 Aug 1;146:420-6. doi: 10.1016/j.carbpol.2016.03.003. Epub 2016 Mar 6.
Chitosan has great potential as a pharmaceutical excipient. In this study, chitosan flake was micronized using cryo-ball and cryo-jet milling and subsequently sterilized with nitrogen plasma. Micronized chitosan was characterized by laser diffraction, scanning electron microscopy (SEM), conductometric titration, viscometry, loss on drying, FTIR, and limulus amebocyte lysate (LAL) assays. Cryo-jet milling produced mean particle size of 16.05μm, 44% smaller than cryo-ball milling. Cryomilled chitosan demonstrated increased hygroscopicity, but reduced molecular weight and degree of deacetylation (DD). SEM imaging showed highly irregular shapes. FTIR showed changes consistent with reduced DD and an unexplained shift at 1100cm(-1). Plasma treated chitosan was sterile with <2.5EU/g after low-pressure plasma and <1.3EU/g after atmospheric pressure plasma treatment. Plasma treatment decreased the reduced viscosity of chitosan flake and powder, with a greater effect on powder. In conclusion, pharmaceutical grade, sterile chitosan powder was produced with cryo-jet milling and plasma sterilization.
壳聚糖作为药物辅料具有巨大潜力。在本研究中，使用低温球磨和低温喷射研磨将壳聚糖薄片微粉化，随后用氮等离子体进行灭菌。通过激光衍射、扫描电子显微镜（SEM）、电导滴定、粘度测定、干燥失重、傅里叶变换红外光谱（FTIR）和鲎试剂（LAL）分析对微粉化壳聚糖进行表征。低温喷射研磨产生的平均粒径为16.05μm，比低温球磨小44%。冷冻研磨的壳聚糖表现出吸湿性增加，但分子量和脱乙酰度（DD）降低。SEM成像显示形状高度不规则。FTIR显示出与DD降低一致的变化以及在1100cm(-1)处无法解释的位移。等离子体处理后的壳聚糖在低压等离子体处理后无菌，每克<2.5内毒素单位（EU），在大气压等离子体处理后每克<1.3EU。等离子体处理降低了壳聚糖薄片和粉末的比浓粘度，对粉末的影响更大。总之，通过低温喷射研磨和等离子体灭菌制备出了药用级无菌壳聚糖粉末。
