超临界流体强制分散溶液技术及其在药物领域的应用

超临界流体强制分散溶液技术以其独特的优点,在药物超细化和微胶囊化等方面得到了广泛的应用。介绍了该技术的基本原理及工艺改进的研究情况,综述了该技术在药物及药物载体超细微粒和药物微囊制备方面的应用进展。利用SEDS过程能制备粒度分布窄的微米级甚至纳米级的微粒,能够将残留溶剂减小到非常低的质量浓度并且容易控制微粒粒径及粒度分布。     

Fine milling and micronization of organic and inorganic materials under dynamic conditions

Milling and micronization of whey protein concentrate (WPC) and zeolite (type clinoptilolite) were carried out. In this work, samples were treated using laboratory equipment for tribomechanical micronization (TMA equipment) at three different rotor speeds. Before and after the tribomechanical treatment, analysis of the particle size and particle size distribution, as well as the specific area, was carried out, in addition to scanning microscopy.A suspension of the investigated materials was treated with ultrasound (1-10 min) immediately prior to determining the particle size distribution.The results showed that the TMA treatment causes a significant decrease in particle size, a change in particle size distribution, and an increase in specific area of WPC and zeolite. These changes in the treated materials depend on the type of the material and the rotor speed of the TMA equipment.The most significant changes in tested materials were observed in samples treated at the maximum rotor speed (22,000 rpm) of the tribomechanical micronization device.As a consequence of the ultrasonic treatment of the suspension of tribomechanically treated WPC, further destruction of partly damaged protein globules occurs. Ultrasonic treatment of the suspension of tribomechanically treated zeolite produced no significant change in its granulometric composition.     

Evaluation of the impact of sodium lauryl sulfate source variability on solid oral dosage form development

Objective: The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. Methods: The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. Results: The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. Conclusions: The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance.     

Extraction of β–glucan by hydrothermal liquidization of barley grain in a semi-batch reactor

Subcritical water is a natural and green way for extraction of plant biomass components. Here, subcritical water was employed as a media to extract β–glucan from barley (Hordeum vulgare L.) at 130–170°C and 10 MPa. MALDI TOF–MS revealed that main massed peaks of water soluble products were distributed at 500-2900 m/z with a peak to peak mass difference of 162 m/z, consistent with the repeating unit of β–glucan. At 170°C, all amount of water soluble β–glucan has been extracted. Next, the liquid fraction products were atomized directly to produce microsphere particles.     

超微粉碎冷榨火麻粕对法兰克福香肠品质特性的影响

研究不同添加量（0%、0.5%、1.0%、1.5%、2.0%、2.5%）的超微粉碎冷榨火麻粕（micronized cold pressed hemp meal,MCPHM）对法兰克福香肠品质特性的影响。结果表明：随着MCPHM添加量的增加,法兰克福香肠的蒸煮损失、乳化稳定性、硬度、弹性及咀嚼性呈现先增加后降低的趋势（P<0.05）;法兰克福香肠的水分活度随着MCPHM添加量的增加而显著降低,而pH值则显著增加（P<0.05）。因此,MCPHM能够有效改善法兰克福香肠的品质,并且在添加量为1.0%时具有最佳改善效果。     

Control of the Particle Size of Submicron HMX Explosive by Spraying in Non-Solvent

Preparation and characterization of cyclotetramethylene tetranitramine (HMX; octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) submicron particles by spraying in non-solvent technology at different process parameters was investigated in this article. The results indicated that the process parameters, such as addition of surfactant, slurry, and anti-solvent temperatures; compressed air flow rate; slurry flow rate; stirring the anti-solvent; and nozzle diameter played important roles in controlling the performance of HMX submicron particles, such as particle size, size distribution, etc. The produced HMX particles by spraying in a non-solvent method were identified and characterized by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The results showed that this method is simple for micronization of energetic materials and would be an effective method for large-scale preparation of submicron particles of HMX explosive. Finally, the optimum condition for the preparation of fine powder of HMX by spraying in a non-solvent method was proposed.     

水溶胶冻干法制备微粉化辛伐他汀

利用反溶剂沉淀法,以甲醇为溶剂,水为反溶剂,将辛伐他汀的甲醇溶液与水混合,形成水溶胶,用液氮速冻,经冷冻干燥,得到微粉化的辛伐他汀.并利用扫描电镜(SEM)、X射线衍射(XRD)、红外光谱分析(FT-IR)、差热分析(DSC)、比表面分析(BET)等分析方法对产品的特性进行了表征,此外还测定了微粉化后产品的溶解速率,并和原料进行了对比.结果表明,辛伐他汀粉体粒度随水与甲醇的混合体积比的增加和辛伐他汀的甲醇溶液浓度的减小而减小,同时团聚减小.而混合温度与转速对产品粒径影响不大.当水与甲醇溶液的混合体积比为10:1,辛伐他汀的甲醇溶液浓度为0.1 mol·L-1时,所得药物颗粒为纤维状,短径在500 nm左右,比表面可达10 m2·g-1以上,同时溶解速率比原粉提高近10倍.     

微粉碎甘薯原料的生料发酵

采用糖化酶和酵母菌,对粗粉碎、微粉碎两种不同粒径的甘薯进行生料发酵,探讨微粉碎甘薯生料发酵的可行性;并通过正交试验,调查中温α-淀粉酶、糖化酶和酒精酶三种酶用量对微粉碎甘薯生料发酵影响的显著性。试验结果表明,微粉碎甘薯生料发酵的速率和酒精度均显著高于粗粉碎甘薯;初始pH在5.0~5.5的范围内,发酵效果最好;酒精酶对微粉碎甘薯生料发酵具有显著性影响,在中温α-淀粉酶10 u/g、糖化酶500 u/g和酒精酶0.2%的条件下生料发酵,最高酒精度为10.7%,其原料淀粉的转化率达到82.5%。由此可见,通过微粉碎,可实现甘薯的生料发酵。     

超临界溶液浸渍法制备缓释药物

超临界溶液浸渍法(supercritical solution impregnation,SSI)是一种将小分子物质负载到聚合物中的过程技术,主要是利用超临界流体的高扩散系数、低黏度及其对聚合物的溶胀作用,使小分子物质通过分子扩散作用迅速进入溶胀的聚合物并包裹于其中。近年来该技术已用于制备缓释药物/聚合物复合微球、薄膜和纤维等。该法的主要优点在于载体结构灵活,拓展了超临界技术在控释药物制备中的应用。本文主要介绍了SSI法的原理、流程及其在缓释药物制备中的应用,并展望了SSI法的发展趋势。