超微粉碎对罗勒显微特征及总黄酮体外溶出的影响简

目的：对罗勒超微粉和常规粉中总黄酮的体外溶出、显微特征及粉体学性质进行考察.方法：采用比色法测定罗勒超微粉和常规粉中总黄酮体外溶出量和溶出速率,用生物显微镜进行显微特征观察,测定粉体休止角和堆密度.结果：罗勒超微粉和常规粉中总黄酮体外溶出量无显著性差异,超微粉体的溶出速率较常规粉体明显增加.罗勒超微粉颗粒均匀,基本无完整细胞存在.与常规粉相比,罗勒超微粉的休止角增大,堆密度减小.结论：超微粉碎不会影响总黄酮的体外溶出量,但可明显提高其溶出速率.植物细胞破壁率明显提高,但流动性和充填性变差,有待于在制剂生产中进行改进.     

云木香普通粉与超微粉挥发性成分的对比研究

目的对比研究云木香普通粉和超微粉中的挥发性成分。方法利用水蒸气蒸馏法分别提取云木香根两种粉末中的挥发油成分,用GC-MS进行测定,结合计算机检索技术对分离的化合物进行结构鉴定,归一化法计算两种粉末中各成分的相对含量。结果云木香普通粉中分离鉴定出53个化学成分,占挥发油总量的99.07%;超微粉中分离鉴定出46个化学成分,占挥发油总量的96.86%。两种粉末挥发性成分中有46种相同成分,超微粉中含量高于普通粉中相应成分的有29种。结论本文首次对云木香根普通粉和超微粉挥发性成分进行了对比研究,为其研究应用提供科学依据。     

超微粉碎对当归中基本化学成分溶出的影响

目的比较不同粒径当归药材中阿魏酸及其他化学成分溶出的情况。方法采用高效液相色谱法分别对当归超微粉和40目、100目普通粉中所含化学成分进行定量、定性研究。结果以超声处理10min为条件,当归超微粉中的阿魏酸溶出量分别比40目、100目普通粉提高了82．51％和81．09％。在所含基本化学成分的图谱中,超微粉谱图的峰数较多,即溶出的物质较多,且在共有峰中超微粉的相对峰面积较大。结论超微粉碎能明显提高当归药材中化学成分溶出。     

超微粉碎技术对灵芝中三萜类成分溶出的影响

目的:研究超微粉碎技术对灵芝中三萜类成分溶出的影响。方法:采用紫外-可见分光光度法测定灵芝中三萜类成分总提取率,高效液相色谱法(HPLC)测定灵芝中9种三萜类成分(灵芝酸A、灵芝酸B、灵芝酸C、灵芝酸C1、灵芝酸C2、灵芝酸D、灵芝酸E、灵芝酸G、灵芝酸H)含量,比较30、50、80目灵芝普通粉和300目灵芝超微粉中三萜类成分总提取率及9种三萜类成分的含量。结果:30、50、80、300目灵芝粉中三萜类成分总提取率分别为(0.74±0.08)%、(0.75±0.06)%、(0.78±0.06)%、(1.09±0.10)%(RSD<2%,n=3);随着灵芝粉目数的增大,三萜类成分含量逐渐增大,其中300目含量最大,显著高于灵芝普通粉(P<0.05)。结论:灵芝经超微粉碎后三萜类成分的溶出增加。     

超微粉碎对牡蛎壳粉体学性质和溶出度的影响

目的:考察超微粉碎对牡蛎壳粉体学性质和溶出度的影响,为牡蛎壳综合开发利用提供实验依据。方法:牡蛎壳以粉碎机制备成普通粉,再将普通粉以超微粉碎机制备成微粉Ⅰ(粉碎5 min)和微粉Ⅱ(粉碎10 min)。从粉体粒径分布、比表面积、孔隙度、休止角、堆密度、吸湿率等方面考察牡蛎壳超微粉碎前后的粉体学差异,采用扫描电镜、傅里叶变换红外光谱(FTIR)和X射线衍射(XRD)等分析其形态特征和化学结构的变化情况,并考察其溶出度。结果:与普通粉比较,微粉Ⅰ和微粉Ⅱ粒径小且分布均匀,但粒子易黏附聚集,比表面积、孔隙度及休止角增大,堆密度减少,吸湿性增强;FTIR和XRD图谱显示牡蛎壳超微粉碎后化学结构无明显变化。微粉Ⅱ和微粉Ⅰ在10 min时溶出度分别为18.5%和10.3%,普通粉在60 min时溶出度只有6.4%。结论:与普通粉比较,牡蛎壳超微粉碎后的粉体学性质呈现出明显差异,粉体溶出度增加,化学结构未发生明显变化。     

柴葛退热散超微粉碎工艺优化

目的:优化柴葛退热散超微粉碎工艺;比较超微粉和普通细粉中有效成分的含量和显微特征。方法:以柴葛退热散中3种有效成分(葛根素、甘草苷和黄芩苷)的含量以及粉末d(0.5)为主要指标,以堆密度、休止角及显微特征为参考指标,设计正交试验对超微粉碎工艺中粉末的初始粒径、水分及粉碎频率进行优化。比较超微粉与普通细粉(过65/80目筛)中3种有效成分的含量及显微镜下草酸钙针晶的观察结果。结果:超微粉优化工艺为选择初始粒径为过65目筛、水分为2.5%的药材粉末在粉碎频率为60 Hz下粉碎;验证试验中3份超微粉样品的d(0.5)平均值为31.5μm(RSD=0.45%,n=3),其中葛根素、甘草苷和黄芩苷的含量分别为0.232、0.212、8.962 mg/g(RSD分别为1.31%、1.62%、0.89%,n=3),比普通细粉中3种有效成分含量(0.158、0.160、6.140mg/g)约高30%~40%。超微粉中未见或仅少量可见普通细粉中常见的成束草酸钙针晶。结论:优化的超微粉碎工艺稳定、可行;柴葛退热散超微粉中3种有效成分的含量高于普通粉中含量,且因草酸钙针晶的减少有可能减少其临床不良反应。     

番泻叶超微饮片与不同粉体溶出度的比较研究

目的:比较番泻叶超微饮片与不同粉体的体外溶出特性。方法:采用桨法进行体外溶出试验,高效液相色谱法测定番泻叶超微饮片与不同粉体不同时间点番泻苷A和番泻苷B的溶出量,计算累积溶出百分率,并对其进行威布尔分布函数拟合。结果:番泻叶中粉、细粉、超微粉与超微饮片之间的溶出速度具有明显差异,超微饮片中番泻苷A和番泻苷B的溶出量最大,累积溶出70%的时间明显小于其他粉体。结论:番泻叶超微饮片具有快速溶出、高效溶出有效成分的特点。     

党参超微粉对胃溃疡模型大鼠胃黏膜保护作用的研究

目的 研究比较党参超微粉与普通粉对胃溃疡大鼠模型胃黏膜损伤的保护作用。方法 制备乙酸致胃粘膜损伤型大鼠胃溃疡模型,经两种粉末治疗10天后,测定溃疡面积,计算溃疡指数,并比较;分别用放免法检测各组大鼠血清中Gas及血浆中6-keto-PGF1α含量,并采用酶联免疫法测定血清中EGF含量,并比较。结果 两组组大鼠溃疡指数均低于模型组,且超微粉组明显低于普通粉组;超微粉组大鼠血清Gas含量低于普通粉组, 6-keto-PGF1α和EGF含量高于普通粉组。结论 党参超微粉对胃溃疡的疗效优于普通粉,超微粉碎有助于提高党参药效。     

超微粉碎技术对牡丹皮主要成分含量的影响

目的初步探讨超微粉碎技术对牡丹皮中丹皮酚、芍药苷含量的影响。方法采用HPLC法测定牡丹皮超微粉与细粉粉体中丹皮酚与芍药苷的含量。结果牡丹皮采用振动磨低温超微粉碎,可较好保留丹皮酚;常温与低温超微粉碎,芍药苷溶出量超微粉较细粉分别提高8.11%、8.65%。结论初步表明振动磨低温粉碎可用于牡丹皮超微粉体的制备。     

超微粉碎技术对苍术粉体理化性质的影响

目的探讨超微粉碎技术对苍术粉体理化性质的影响。方法采用振动磨常温和低温超微粉碎,考察温度对苍术粉体挥发油、苍术素含量及物理性质的影响。结果常温下(20℃)超微粉碎可造成挥发油的损失18.58%,低温(-15℃)粉碎可避免挥发油的损失;与苍术细粉比较,超微粉体红外吸收光谱基本没有改变,低温超微粉碎可较好保留热敏性成分。结论初步表明振动磨低温粉碎可用于苍术超微粉体的制备。     

An overview on in situ micronization technique – An emerging novel concept in advanced drug delivery

The use of drug powders containing micronized drug particles has been increasing in several pharmaceutical dosage forms to overcome the dissolution and bioavailability problems. Most of the newly developed drugs are poorly water soluble which limits dissolution rate and bioavailability. The dissolution rate can be enhanced by micronization of the drug particles. The properties of the micronized drug substance such as particle size, size distribution, shape, surface properties, and agglomeration behaviour and powder flow are affected by the type of micronization technique used. Mechanical communition, spray drying and supercritical fluid (SCF) technology are the most commonly employed techniques for production of micronized drug particles but the characteristics of the resulting drug product cannot be controlled using these techniques. Hence, a newer technique called in situ micronization is developed in order to overcome the limitations associated with the other techniques. This review summarizes the existing knowledge on in situ micronization techniques. The properties of the resulting drug substance obtained by in situ micronization were also compared.     

当归超微粉直接压片工艺研究

目的:研究当归超微粉直接压片成型的工艺。方法:采用混料均匀设计法,以片重差异、脆碎度为限制条件,以硬度、崩解度的综合评分为指标建立回归方程,求出综合最优解,对当归超微粉片处方进行优化。用DPS软件进行数据运算。结果:最佳处方为应用粉末直接压片法制备片剂,其硬度可达到75N,崩解时间为10.24min,且片面光滑无缺。结论:该工艺处方合理、成型性好,可为工业化生产提供理论依据。     

Spray freezing into liquid (SFL) particle engineering technology to enhance dissolution of poorly water soluble drugs: organic solvent versus organic/aqueous co-solvent systems.

A spray freezing into liquid (SFL) particle engineering technology has been developed to produce micronized powders to enhance the dissolution of poorly water soluble active pharmaceutical ingredients (APIs). Previously, a tetrahydrofuran (THF)/water co-solvent was used as the solution source in the SFL process. In the present study, an organic system was developed to further enhance the properties of particles produced by SFL. The influence of solution type (e.g. organic versus organic/water) on the physicochemical properties of SFL powders was investigated and compared. The physicochemical properties of SFL carbamazepine (CBZ)/poloxamer 407/PVP K15 (2:1:1 ratio) powders were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size distribution, surface area analysis, contact angle measurement, Karl-Fisher (KF) titration, gas chromatography (GC) analysis, HPLC analysis, and dissolution testing. The CBZ loading in the feed solution of the SFL acetonitrile system was 2.2% (w/w), which was greater than 0.22% (w/w) loading of the THF/water co-solvent system. XRD results indicated CBZ was amorphous in SFL powders produced by either system. SEM micrographs indicated that SFL powders from acetonitrile appeared less porous with a smaller primary particle size than particles from the co-solvent. The M50 (50% cumulative percent undersize) of micronized powder from the SFL acetonitrile system and the THF/water co-solvent system with 0.22% CBZ loading were 680nm and 7.06microm, respectively. The surface area of SFL powders from the acetonitrile and co-solvent systems were 12.89 and 13.31m(2)/g, respectively. The contact angle of the SFL powders against purified water was about 35 degrees for both systems. The SFL powders from both systems exhibited similar and significantly enhanced dissolution rates compared to the bulk CBZ. Acetonitrile was an effective alternative solvent to THF/water co-solvent for use with the SFL micronization process to produce free flowing particles containing CBZ with significantly enhanced wetting and dissolution properties.     

田口实验设计法优选当归中阿魏酸的提取工艺

目的:以正交试验为基础,探讨田口实验设计法优选当归的最佳提取工艺的可行性。方法:以阿魏酸为指标,以L9(34)正交表安排正交试验,采用田口实验设计原理分析实验结果,优选影响提取工艺的4个因素:乙醇用量(A)、乙醇浓度(B)、提取次数(C)和提取时间(D)。结果:最优提取工艺为8倍量的70%乙醇,提取3次,每次1 h。结论:以正交试验为基础,田口实验设计法可优选当归中阿魏酸的提取工艺,增加提取率,并为优选其他中药有效成分的提取工艺辟出新途径。     

Micronized powders of a poorly water soluble drug produced by a spray-freezing into liquid-emulsion process.

The purpose of this paper is to investigate the influence of the emulsion composition of the feed liquid on physicochemical characteristics of drug-loaded powders produced by spray-freezing into liquid (SFL) micronization, and to compare the SFL emulsion process to the SFL solution process. Danazol was formulated with polyvinyl alcohol (MW 22,000), poloxamer 407, and polyvinylpyrrolidone K-15 in a 2:1:1:1 weight ratio (40% active pharmaceutical ingredient (API) potency based on dry weight). Emulsions were formulated in ratios up to 20:1:1:1 (87% API potency based on dry weight). Ethyl acetate/water or dichloromethane/water mixtures were used to produce o/w emulsions for SFL micronization, and a tetrahydrofuran/water mixture was used to formulate the feed solutions. Micronized SFL powders were characterized by X-ray diffraction, surface area, scanning and transmission electron microscopy, contact angle and dissolution. Emulsions containing danazol in the internal oil phase and processed by SFL produced micronized powders containing amorphous drug. The surface area increased as drug and excipient concentrations were increased. Surface areas ranged from 8.9 m(2)/g (SFL powder from solution) to 83.1 m(2)/g (SFL powder from emulsion). Danazol contained in micronized SFL powders from emulsion and solution was 100% dissolved in the dissolution media within 2 min, which was significantly faster than the dissolution of non-SFL processed controls investigated (<50% in 2 min). Micronized SFL powders produced from emulsion had similar dissolution enhancement compared to those produced from solution, but higher quantities could be SFL processed from emulsions. Potencies of up to 87% yielded powders with rapid wetting and dissolution when utilizing feed emulsions instead of solutions. Large-scale SFL product batches were manufactured using lower solvent quantities and higher drug concentrations via emulsion formulations, thus demonstrating the usefulness of the SFL micronization technology in pharmaceutical development.     

Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes. Part I: Micronization of neat particles

In this first of two articles, we discuss some issues surrounding the dissolution rate enhancement of poorly-soluble active ingredients micronized into nano-particles using several supercritical fluid particle design processes including rapid expansion of supercritical solutions (RESS), supercritical anti-solvent (SAS) and particles from gas-saturated solutions/suspensions (PGSS). Experimental results confirm that dissolution rates do not only depend on the surface area and particle size of the processed powder, but are greatly affected by other physico-chemical characteristics such as crystal morphology and wettability that may reduce the benefit of micronization.     

Effect of particle shape of active pharmaceutical ingredients prepared by fluidized-bed jet-milling on cohesiveness

Milling is a common procedure to improve bioavailability of many active pharmaceutical ingredients (APIs), which typically have low solubility in water. But such micronization can yield an increase in the cohesiveness of particles. Although particle cohesiveness is desirable for tablet strength in the subsequent formulation process, increased particle cohesiveness can lead to operational difficulties in a milling equipment due to compaction of particles inside. In this article, the impact of milling via a fluidized-bed jet-mill on the cohesive strength and interparticle force was studied using Ethenzamide as a pharmaceutical model compound. As a result, the particle shape was found to affect both the tensile strength of powder bed and the interparticle cohesive force. A powder bed, having relatively high void fraction by direct tensile test, shows a positive correlation between the cohesive force and the particle sphericity, while powders with low void fraction by diametral compression test show a positive correlation between the cohesive force and the angularity of the particle.     

Simultaneous micronization and surface modification for improvement of flow and dissolution of drug particles

Simultaneous micronization and surface modification of drug particles is considered in order to mitigate disadvantages of micronization, e.g., agglomeration, poor flowability, marginal increase in surface area and low bulk density. Particles of ibuprofen (102 μm), a model drug, pre-blended with hydrophilic nano-silica, are micronized down to 10 and 5 μm in a continuous fluid energy mill (FEM) to obtain fine surface modified particles. The solid feeding rate and the grinding pressure are shown as critical parameters for achieving the desired particle size and size distribution. The powder properties were characterized via SEM, laser scattering, powder rheometer with shear-cell, and dissolution test. Significant improvement in flow properties and dissolution rate was observed when micronization accompanied surface modification. Additionally, co-grinding with water-soluble polymer during micronization led to further increase in bulk density and more enhanced dissolution rate improvement, which is attributed to improved wettability. XRD, DSC and Raman were used to examine crystallinity, indicating minimal detectable physical transformation with FEM processed ibuprofen. The surface modified, micronized powders also showed improved dispersion, higher bulk densities (>0.4 g/ml), reduced electrostatic, and higher flowability (FFC ≥ 6) compared to just micronized powder (0.19 g/ml, FFC=1.0), indicating they may be used in high drug loaded formulations amenable to direct compression.     

The importance of micronization in the design of dosage forms I. Theoretical and biopharmaceutical aspects

The role of micronization is growing considering the optimization of the physicochemical characteristics of drug, dissolution enhancement and ensuring appropiate bioavailability. The importance of micronization can be understood on the basis of Noyes-Whitney equation, where the particle characteristics influence the active surface contacting with the dissolution medium, theoretically the solubility, and the boundary layer around the particle under certain hidrodynamic conditions. To adjudge the possibilities and limits of micronization concerning the dosage form design and preparations based on innovative pharmaceutical technology, it is necessary to take the detailed theoretical, physiological and biopharmaceutical aspects into consideration.     

螺旋霉素超细粉的喷干法和反溶剂法制备及性质研究

目的 螺旋霉素原料药粉的粒径大、团聚现象严重,因此极大的限制了其临床应用;有研究报道超细粉制备技术可以很好地解决这些问题;方法 采用了两种代表性的方法制备螺旋霉素的超细粉：分别为喷雾干燥法和反溶剂法;并以粒径为指标,采用单因素实验优化得到最佳结果,对上述两种方法制备的粉体分别进行粒径、形貌特征和物化性质对比。结果 两种方法的最佳条件为：喷雾干燥法的进料速度为5 mL/min,雾化空气速度为800 L/h,进口温度为150℃,出口温度为85℃,平均粒径为(1638±10.99) nm。反溶剂法在25℃条件进行实验,溶剂与反溶剂的比例为1:5,最佳搅拌速度为1000 r/min,获得的平均粒径为(230±7.31)nm,以上结果经过扫描电子显微镜(SEM),动态光散射(DLS),傅立叶变换红外光谱(FTIR),差示扫描量热仪(DSC)和X射线衍射(XRD)进行表征;经气相色谱检测,两种方法中的溶剂残留均符合ICH最低标准(5000 ppm);结论 与喷雾干燥法相比,反溶剂法制备的螺旋霉素粒径更小、粉体分散性更佳,其溶解度更高。因此反溶剂法制备的螺旋酶素微粉更适用于制药业,为微粉技术提供技术...