化橘红不同粒径粉末的粉体特性及体外溶出实验研究

目的比较化橘红不同粒径粉末的粉体学特性和体外溶出特点,探索超微粉碎技术在中药化橘红中的应用。方法采用激光粒度分析仪测定粉末粒径;采用生物显微镜观察不同粒径粉末的显微特征;采用固定漏斗法测定休止角;采用高效液相色谱法测定化橘红不同粒径粉末中柚皮苷的体外溶出度。结果化橘红超微粉碎前后粉末的粉体学特征、有效成分的溶出量差异较大,超微粉中柚皮苷的相对累积溶出率高于普通粉碎所得粉末。结论化橘红微粉化可使植物药细胞破壁,促进有效成分的溶出。     

微粉化对马钱子溶出度的影响

目的 考察微粉化时制马钱子中士的宁、马钱子碱溶出度的影响.方法 采用《中华人民共和国药典》2010年版二部附录溶出度浆法,用HPLC测定,分别在人工胃液和人工肠液(无酶)模拟体内环境的溶出介质下,转速50r/min,体积为900 mL,比较微粉化前后马钱子粉的溶出行为.结果 以T50、Td、T90为溶出度参数,在人工肠液中,以马钱子碱、士的宁为考察指标,马钱子超微粉分别为0.38、1.33、19.50,0.39、1.31、17.63 min;马钱子粗粉分别为19.43、44.53、249.12,20.84、44.96、229.95 min.在人工胃液中,以马钱子碱、士的宁为考察指标,马钱子超微粉分别为0.32、1.25、20.60,0.45、1.41、20.81 min;马钱子粗粉分别为20.53、43.31、220.30,20.76、46.02、241.82 min,两者比较差异均有统计学意义(P＜0.01).结论 微粉化能提高马钱子中士的宁、马钱子碱的溶出量与溶出速度.     

Developing an environmentally benign process for the production of microparticles: Amphiphilic crystallization

The production of microparticles for inhalation typically employs jet-milling which can be destructive to the solid-state properties of the particles. The objective of the current work was to develop a crystallization process for the production of respirable microparticles of salmeterol xinafoate (SX) with a controlled particle size distribution (PSD). Solvation of SX in aqueous poly(ethylene glycol) 400 (PEG 400) was investigated using HPLC and FTIR. SX was crystallized from PEG 400 solutions by the addition of water under a variety of conditions of supersaturation, addition rate of antisolvent and stirring speed. The crystals were filtered, dried at 50 °C and their PSDs were determined by laser diffraction. A logarithmic increase in solubility of SX was observed with increasing concentration of PEG 400 in water enabling the aqueous antisolvent crystallization of SX from PEG. Similar to antisolvent crystallization from conventional solvents, a 2⁴ factorial study showed the particle size to decrease with increasing supersaturation. The PSD also depended on the balance of meso- and micromixing determined by the crystallization conditions. In particular a high addition rate (200 g min⁻¹) and low stirrer speed (400 rpm) minimized the median diameter (2.54 ± 0.40 μm) and produced a narrow PSD (90% < 8.67 ± 0.77 μm) of SX particles. Amphiphilic crystallization provided a novel, environmentally benign method to produce microparticles of SX with a controlled size range.     

不同蒸制时间对栀子质量的影响

目的：考察和比较不同基质、不同药材粉碎度的新工艺三黄栓的体外释药性能。方法：制备水溶性基质（聚乙二醇-6000）三黄细粉栓及微粉栓,油脂性基质（混合脂肪酸甘油酯）三黄细粉栓及微粉栓。采用UV测定体外溶出度,检测波长272 nm,计算累积溶出率,通过威布尔分布模型提取溶出度参数,考察并比较各三黄栓的体外释药特性。结果：新工艺三黄栓较传统油脂性基质三黄栓的体外溶出度显著提高。三黄微粉栓（聚乙二醇-6000）的T20（药物溶出20%所用时间）,T50（药物溶出50%所用时间）,Td（药物溶出63.2%所用时间）分别为3.84,11.34,16.09 min。结论：基质及药材粉碎度对三黄栓体外溶出度均具有显著影响,水溶性基质三黄微粉栓释药迅速而充分,传统油脂性基质三黄栓中药物难以充分释放。     

诺氟沙星微粉化制剂溶出特性的研究

诺氟沙星经微粉化后，平均粒径为１．３７μｍ。在实验选定的配方条件下，微粉化诺氟沙星颗粒显示较好的溶出特性，粘合剂和崩解剂对主药溶出速率的影响分别以阿拉伯胶及乳糖为最好。同时考察了不同的溶出介质对溶出的影响，主药在人工肠液中溶出最快，而在蒸馏水和吐温－８０溶液中溶出情况近似。     

Generation of Fine Powders of Recombinant Human Deoxyribonuclease Using the Aerosol Solvent Extraction System

PURPOSE: To investigate the feasibility of using the Aerosol Solvent Extraction System (ASES) to produce fine powders of recombinant human deoxyribonuclease (rhDNase), lysozyme-lactose and rhDNase-lactose powders from aqueous based solutions. METHODS: The ASES technique using high pressure carbon dioxide modified with ethanol or ethanol and triethylamine was used for the generation of rhDNase powders and protein-lactose powders from aqueous based solutions. Particle size, morphology, size distributions, crystallinity, and powder aerosol performance were measured. The biochemical integrity of the processed rhDNase was assessed by testing the monomer content and the degree of deamidation. RESULTS: RhDNase precipitated as spherical particles in the size range between 50 and 500 nm. The primary nano-sized particles were agglomerated to micron-sized clumps of particles during the precipitation process. The median particle size and the fine particle fraction were functions of the operating temperature and the nozzle system used. RhDNase was substantially denatured in the ASES process using carbon dioxide modified with ethanol as anti-solvent. However almost complete recovery of the monomer was achieved using carbon dioxide modified with ethanol-triethylamine as an anti-solvent. Lysozyme-lactose and rhDNase-lactose powders were also precipitated as agglomerated spheres using the ASES process. The powders were amorphous except for those with lactose content higher than 45%. CONCLUSIONS: Micron-sized particles of rhDNase suitable for inhalation delivery were generated from aqueous based solutions using the modified ASES technique. The biochemical integrity of the rhDNase powder is a function of the antisolvent and the operating temperature.     

Application of dense gas techniques for the production of fine particles

The feasibility of using dense gas techniques such as rapid expansion of supercritical solutions (RESS) and aerosol solvent extraction system (ASES) for micronization of pharmaceutical compounds is demonstrated. The chiral nonsteroidal anti-inflammatory racemic ibuprofen is soluble in carbon dioxide at 35°C and pressures above 90 bar. The particle size decreased to less than 2 μm while the degree of crystallinity was slightly decreased when processed by RESS. The dissolution rate of the ibuprofen (a poorly water-soluble compound) was significantly enhanced after processing by RESS. The nonsteroidal anti-inflammatory drug Cu₂(indomethacin)₄L₂(Cu-Indo); (L=dimethylformamide [DMF]), which possessed very low solubility in supercritical CO₂, was successfully micronized by ASES at 25°C and 68.9 bar using DMF as the solvent and CO₂ as the antisolvent. The concentration of solute dramatically influenced the precipitate characteristics. The particles obtained from the ASES process were changed from bipyramidal to spherical, with particle size less than 5 μm, as the concentration increased from 5 to 100 mg/g. A further increase in solute concentration to 200 mg/g resulted in large porous spheres, between 20 and 50 μ, when processing Cu-Indo by the ASES method. The dissolution rate of the micronized Cu-Indo was significantly higher than the commercial product.     

超临界溶液快速膨胀法制备灰黄霉素微粒

采用含有夹带剂丙酮的超临界溶液快速膨胀法制备灰黄霉素超细颗粒.所得微粒粒径约1μm.减小喷嘴孔径、提高夹带剂浓度或降低预膨胀温度均可使微粒粒径减小.     

Micronized Oat Husk: Particle Size Distribution,Phenolic Acid Profile and Antioxidant Properties

Oat husk (OH; hull) is a by-product generated from oat processing and is rich in insoluble fibre and phenolic compounds. The aim of this work was to study the particle size distribution, antioxidant activity, and phenolic profile of micronized OH. For this purpose, the hull was first sterilized using superheated steam and was then ground using an impact classifier mill. The particle size distribution (PSD) of the ground husk was determined using the laser diffraction method and the parameters characterizing the PSD of the ground husk, and its antioxidant activity were calculated. In addition, UPLC-MS/MS analysis of phenolic acids was also performed. Micronization of the sterilized husk effectively decreased the size of the particles, and with the increasing speed of the rotor and classifier, the median size of the particles (d₅₀) decreased from 63.8 to 16.7 µm. The following phenolic acids were identified in OH: ferulic, caffeic, p-hydroxybenzoic, vanillic, syringic, and synapic acid. Ferulic acid constituted about 95% of total phenolic acids. The antioxidant activity of the obtained extracts increased as the particle size of the micronized husk decreased. The highest half maximal inhibitory concentration (EC₅₀ index) was found for chelating power, and the lowest was found in the case of radical scavenging activity against DPPH.     

黄芩超微粉与普通粉溶出度比较

目的:研究微粉化技术对中药材黄芩显微特征、溶出度的影响。方法:观察黄芩普通细粉和超微粉的显微特征,并采用紫外分光光度法测定其中黄芩苷的含量。结果:黄芩苷含量超微细粉(<10μm)比普通细粉(80目)提高13.9%。结论:超微粉碎可提高黄芩有效成分的溶出,简化提取工艺,降低成本。