反溶剂重结晶法制备布地奈德超细颗粒及其肺部给药体外评价

利用反溶剂重结晶法对平喘药布地奈德进行了超细颗粒的制备研究.当以甲醇为溶剂,水为反溶剂时,分别考察了甲醇-水的体积比、混合强度和干燥方式对产品平均粒径和收率的影响.结果表明,当布地奈德甲醇溶液与水的体积比为1:7,搅拌转速高于5000r.min-1时,浆料中可得到平均长径3μm、短径2μm、厚度200 nm的椭圆形片状颗粒,并且一次收率为96.02%.将此布地奈德浆料通过真空干燥和喷雾干燥后.产品均可保持浆料中颗粒的大小与形貌,而经喷雾冷冻干燥后则变为10～20 μm左右的球形颗粒.FT-IR和XRD分析显示,与原料药和气流粉碎商品相比,反溶剂重结晶制得的布地奈德的化学结构与晶型均无改变.此外,经肺部给药体外评价,椭圆形片状颗粒具有最优的沉积分布,FPF值高达60%以上,分别比原料药和气流粉碎商品提高了9倍和1.5倍.     

反溶剂重结晶法制备萘普生超细微粒

在溶剂(丙酮)-反溶剂(水)体系下,采用反溶剂重结晶法制备了超细萘普生微粒。研究了不同溶剂-反溶剂体积比、重结晶温度、表面活性剂用量及陈化条件对重结晶产物粒径和形貌的影响。采用扫描电子显微镜(SEM)、表面吸附(BET)、红外光谱(IR)、X射线衍射(XRD)等检测手段对原料药和重结晶产物进行了对比分析。实验结果表明,当溶剂与反溶剂体积比为1:20,重结晶温度为4～8℃,表面活性剂聚乙烯吡咯烷酮(PVP)的质量分数为0.5%～1.0%,60℃下陈化2 h时。可得到短径300～500 nm,长径1～2μm的超细萘普生粉体。重结晶所得产物的晶型和物理性质均未发生变化,但粒度显著减小,形貌趋于规整且比表面积增加至原料药的5.3倍。     

反溶剂超声法制备超细磷酸二氢铵粉体

在溶剂(水)-反溶剂(乙醇)体系下,利用反溶剂超声分散法制备磷酸二氢铵超细粉体,探索得到一种简便、经济的超细粉体制备方法,为后续灭火材料的制备提供基础。研究了超声时间、溶液初始浓度、溶剂-反溶剂体积比、超声功率等条件对磷酸二氢铵粉体形貌和粒径的影响。利用纳米激光粒度仪、扫描电镜、红外光谱、X-射线衍射等对原料和产物进行表征分析。实验结果表明:超声时间为4 min,磷酸二氢铵溶液浓度为0.1 mol/L,溶剂反溶剂体积比为2∶8,超声功率为仪器总功率的9%时,可得粒径500 nm左右的磷酸二氢铵纳米流体;高速离心及真空干燥后,得到粒径2~3μm的固体颗粒产物。     

反溶剂重结晶法制备超细碳酸氢钾粉体

采用反溶剂重结晶法进行了碳酸氢钾微粉化实验研究,通过正交实验确定了影响粉体粒径的因素,如溶液初始浓度、搅拌转速和溶剂反溶剂体积比,对优选条件进行了验证,并采用XRD和激光粒度分析仪对粒子的晶相及粒度分布进行了表征。实验结果表明,当碳酸氢钾水溶液初始质量浓度为100 g/L,搅拌转速为700 r/min,溶剂反溶剂体积比为1∶10时,可制备出平均粒径为491.9 nm且粒度分布较窄的碳酸氢钾超细粉体。     

不同形貌盐酸环丙沙星粉雾剂的制备及其性能研究

盐酸环丙沙星作模型药物,采用溶剂反溶剂法重结晶微粉化,将重结晶浆料直接喷雾干燥,得到由细小针状粒子团聚而成的鸟巢状颗粒;重结晶浆料过滤后经乙醇再分散喷干可得到棒状粒子;重结晶时加入乳糖可以得到绒毛球状粒子.采用多层液体碰撞器(MSLI)对不同形貌的粒子进行体外肺部沉积效果表征,显示微粉化之后的颗粒肺部沉积效果明显变好.     

反溶剂沉淀法制备阿托伐他汀钙微粉

采用反溶剂沉淀法制备阿托伐他汀钙微粉,考察了表面活性剂类型、药物溶液浓度、体系温度和干燥方法对颗粒形貌和大小的影响,得到了适宜的微粉化条件。实验分别利用扫描电镜（SEM）、X射线衍射（XRD）、红外光谱分析（FT-IR）和比表面积（BET）等分析方法对原料及产品的性质进行了表征。研究结果表明：表面活性剂甲基纤维素（MC₂₀）可以有效地控制颗粒形貌;改变溶液浓度及体系温度可以调整颗粒大小;混悬液经喷雾干燥得到的干粉是粒度分布均匀的团粒状类球形颗粒,粒径约为1 μm。微粉化产品为无定形,比表面积高于原料药。此外,还探讨了团粒状类球形颗粒的形成机理。     

反应沉淀法制备阿奇霉素药物超微粉体

利用反应沉淀法进行了阿奇霉素微粉化的实验研究,考察了NaOH溶液浓度、搅拌速度、搅拌时间和反应温度等因素对产品粒度、形貌、分散性及收率的影响. 分别采用扫描电镜(SEM)、比表面分析仪、X射线衍射仪(XRD)和红外光谱仪(FT-IR)对产品进行了分析与表征,并对微粉化产品和原料药进行了溶出性能研究. 实验结果表明,利用此方法可以制备得到平均粒径约为413 nm的无定型阿奇霉素超微粉体,与原料药相比,微粉化的阿奇霉素粉体比表面积增加了约27倍,相应地,药物的溶出性能较原料药明显改善.     

反应结晶法制备阿奇霉素纳米复合粉体

用反应结晶法进行了阿奇霉素纳米化研究,采用扫描电镜( SEM)、比表面分析仪(BET)、X射线衍射仪(XRD)和红外光谱仪(FT-IR)对产品进行了分析与表征,并对纳米复合粉体和原料药进行了溶出性能对比.结果表明,制得阿奇霉素纳米复合粉体平均粒径180 nm左右,与原料药相比,阿奇霉素纳米复合粉体比表面积增加了约15倍,溶出速度较原料药大幅提高.     

青黛超细粉体的制备和性质研究

讨论了球磨制备青黛超细粉体的性质。考察了小磨球尺寸、大小磨球配比、浆料比和充填率对球磨效果的影响,测定了青黛表观真密度、堆密度和比表面积。实验表明通过球磨可以得到平均粒径为40μm以下的青黛粉体,不同平均粒径粉体的表观真密度、堆密度和比表面积均随粒径的减小而增大。球磨所得青黛粉体可以满足改进剂型需要,更利于制作乳剂。     

高纯度高比表面积氧化锡粉体的研制

在硝酸氧化法制备氧化锡粉体基础上,通过改进制备工艺及条件,制得高纯度高比表面积氧化锡粉体,即：在络合能力强的复合有机酸溶液中加入纯度在99.90％以上的高纯锡,形成中间共溶体;向中间共溶体中滴加硝酸和氧化剂进行凝胶化反应,得到灰白色膏状前驱体;向膏状前驱体中滴加氨水进行聚合反应,得到棕色透明液体;棕色透明液体经过滤、喷雾干燥、热处理和粉碎得到氧化锡粉体。产品质量检测结果为：产品纯度为99.90％,中位径为3.5 μm、比表面积为20.79 m²/g、表观密度为0.81 g/cm³。该工艺简单,生产周期短,成本低,易于产业化。     

直接沉淀法超细粉体氧化镁的制备与表征

研究了以硼镁矿生产的工业硫酸镁和草酸铵为起始原料,采用直接沉淀法合成超细粉体氧化镁的简单方法。考察了反应物浓度、加料方式和煅烧温度等因素对粉体质量的影响,初步探索到较好的工艺条件,550℃为最佳煅烧温度。采用红外光谱(IR),热重分析(TG-DTA),X射线粉末衍射(XRD),透射电镜(TEM)等对该纳米微粒的结构进行了表征。结果表明,所制得的纳米氧化镁微粒呈立方晶格,形貌为椭球体,分散性好,粒径在25～35 nm之间。直接沉淀法合成超细粉体氧化镁操作简单,原料易得,生产成本低,产品纯度高,是一种易于工业化的合成方法。     

Determination of Solvent Contamination and Characterization of Ultrafine HNS Particles after Solvent Recrystallization

Solvent–antisolvent recrystallization employed for size reduction of HNS has been described and the effect of various parameters such as stirring rate, effect of antisolvent type, antisolvent temperature, ultrasonication, etc. was investigated. Purified HNS, produced by hot solvent recrystallization of production grade crude HNS, of mean particle size ∼95 μm was used for preparation of ultrafine particles of HNS. Solvent contamination in terms of residual solvent was determined by ¹H NMR and GC‐MS analysis. In addition, ultrafine HNS has been characterized for purity (HPLC, ¹H NMR), particle size and shape (PSA and SEM), specific surface area (BET analysis), thermal behavior (TGA, DSC), sensitivity (impact, friction), etc. The results have been compared with C‐HNS. UF‐HNS was >99% pure with mean particle size <1 μm. SEM showed submicrometer size rods like particles of HNS as the final material.     

Micronization of the Pharmaceutically Active Agent Genipin by an Antisolvent Precipitation Process

Due to its low water solubility and slow dissolution rate, genipin was micronized by an antisolvent precipitation process using ethanol as solvent and n‐hexane as antisolvent. The effects of various experimental parameters on the mean particle size (MPS) of micronized genipin were investigated. By analysis of variance, only the concentration of the genipin solution has a significant effect on the MPS in genipin micronization. Under the optimum conditions, micronized genipin with an MPS of 1.8 μm was obtained. The micronized genipin was characterized by various methods, e.g., scanning electron microscopy and thermogravimetry. The analysis results indicated that the chemical structure of micronized genipin was not changed, but the crystallinity was reduced. The dissolution rate and solubility of the micronized genipin were 2.08 and 1.64 times that of the raw drug. In addition, the residual amounts of n‐hexane and ethanol were less than the International Conference on Harmonization limit for solvents.     

Formation of biodegradable polymeric fine particles by supercritical antisolvent precipitation process

The supercritical antisolvent (SAS) precipitation process as a “green” alternative to specialty particles recrystallization was successfully used to generate poly(L ‐lactide) acid (L‐PLA) from dichloromethane (DCM) solution using CO₂ as antisolvent. The influence of main operating parameters on the synthesis of L‐PLA particles in the SAS process was methodically examined. In particular, antisolvent addition rate (30, 40, 50, and 60 g/min), temperature (35, 40°C, 45°C, and 50°C), solute concentration (50, 75, 100, and 150 mg/10 ml), and solution addition rate (1, 2.5, 5, and 7.5 ml/min). These parameters could be tuned to give a mean particle diameter of 0.62 μm. It was found using scanning electron microscopy and laser diffraction that increasing the antisolvent addition rate and the solution addition rate, while decreasing the temperature and solute concentration, led to a decrease in the L‐PLA mean particle diameter. Furthermore, a unimodal particle size distribution was obtained at the higher solution and antisolvent addition rates. Spherical‐like primary particles have been obtained in all the experimental runs; thus, no change of particle morphology with the process parameters has been noticed. These results manifested that SAS recrystallization process is a valuable technique to generate reproducibly polymer particles with controlled size and size distribution. POLYM. ENG. SCI. 2013. © 2012 Society of Plastics Engineers     

Preparation and Characterization of Micronized Artemisinin via a Rapid Expansion of Supercritical Solutions (RESS) Method

The particle sizes of pharmaceutical substances are important for their bioavailability. Bioavailability can be improved by reducing the particle size of the drug. In this study, artemisinin was micronized by the rapid expansion of supercritical solutions (RESS). The particle size of the unprocessed white needle-like artemisinin particles was 30 to 1200 μm. The optimum micronization conditions are determined as follows: extraction temperature of 62 °C, extraction pressure of 25 MPa, precipitation temperature 45 °C and nozzle diameter of 1000 μm. Under the optimum conditions, micronized artemisinin with a (mean particle size) MPS of 550 nm is obtained. By analysis of variance (ANOVA), extraction temperature and pressure have significant effects on the MPS of the micronized artemisinin. The particle size of micronized artemisinin decreased with increasing extraction temperature and pressure. Moreover, the SEM, LC-MS, FTIR, DSC and XRD allowed the comparison between the crystalline initial state and the micronization particles obtained after the RESS process. The results showed that RESS process has not induced degradation of artemisinin and that processed artemisinin particles have lower crystallinity and melting point. The bulk density of artemisinin was determined before and after RESS process and the obtained results showed that it passes from an initial density of 0.554 to 0.128 g·cm(-3) after the processing. The decrease in bulk density of the micronized powder can increase the liquidity of drug particles when they are applied for medicinal preparations. These results suggest micronized powder of artemisinin can be of great potential in drug delivery systems.     

液相还原法制备超细铜粉的研究进展

超细铜粉具有特殊的性能及广泛的应用前景,针对应用较广泛的液相还原法制备超细铜粉的研究进行了阐述,介绍了液相还原法制备超细铜粉工艺的研究进展以及铜粉表面改性的工艺方法,提出了目前尚存在的问题及对未来的展望。     

Fabrication of composite microparticles of artemisinin for dissolution enhancement

The main aim of this study is to enhance the dissolution of a poorly water soluble antimalarial drug, artemisinin (ART) by fabricating its microparticles and composites with selected hydrophilic polymers using a spray drier with a modified multi-fluid nozzle. We investigated the spray drying of ART with polyvinylpyrrolidone (PVP) considering the effect of feed ratio (ART:PVP) on the physical properties and dissolution of spray dried ART. Other hydrophilic carriers such as polyethylene glycol (PEG) were selected for comparing the dissolution with that of spray dried ART with PVP. The drug and polymer solutions were supplied through different liquid passages of the modified four-fluid nozzle to fabricate ART and composite microparticles. Characterization of the original ART powder, spray dried ART microparticles and ART-polymer composite microparticles was carried out by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and dissolution tester. The DSC and XRD studies suggested that the crystallinity of ART decreased after spray drying and depended on the weight ratio of drug to polymer. Percent dissolution efficiency (%DE); relative dissolution (RD); mean dissolution time (MDT); difference factor (f₁) and similarity factor (f₂) were calculated for the statistical analysis. The dissolution of ART from the spray dried ART-PVP composite microparticles was more rapid than that from their respective physical mixture, spray dried ART-PEG composite microparticles and original ART powder. In the mathematical modeling, the Weibull and Korsmeyer-Peppas model were found to best fit to the in vitro dissolution data and the drug release kinetics could be recognized as Fickian diffusion. This study demonstrated that the modified multi-fluid spray drier can be used for the preparation of drug microparticles to improve the dissolution ability of poorly water soluble drugs and overcome the problem of finding a common solvent for drugs and carriers.     

Micronization of taxifolin by supercritical antisolvent process and evaluation of radical scavenging activity

The aim of this study was to prepare micronized taxifolin powder using the supercritical antisolvent precipitation process to improve the dissolution rate of taxifolin. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters, such as temperature (35-65 °C), pressure (10-25 MPa), solution flow rate (3-6 mL/min) and concentration of the liquid solution (5-20 mg/mL) on the precipitate crystals were investigated. With a lower temperature, a stronger pressure and a lower concentration of the liquid solution, the size of crystals decreased. The precipitation temperature, pressure and concentration of taxifolin solution had a significant effect. However, the solution flow rate had a negligible effect. It was concluded that the physicochemical properties and dissolution rate of crystalline taxifolin could be improved by physical modification such as particle size reduction using the supercritical antisolvent (SAS) process. Further, the SAS process was a powerful methodology for improving the physicochemical properties and radical scavenging activity of taxifolin.