就输液中不溶性微粒的粒径分布谈输液滤器的开发方向

本文就输液中不溶性微粒的粒径分布及输液滤器的开发方向等问题进行了调查及文献复习，并予以讨论。调查结果证明，输液中不溶液微粒的粒径分布状态具有一定规律性，２￣５μｍ的微粒占９８％左右，１０￣２５μｍ的微粒仅占１％￣２％。提示输液滤器的开发需以２￣５μｍ的微粒力依据，使之朝着高效、实用、价廉的方向发展。     

纳米乳的研究及其在制剂学领域的应用

综述纳米乳的制备方法及其粒径和稳定性的影响因素以及在制剂学领域的新应用。纳米乳是由油相、水相、乳化剂和助乳化剂组成的透明或者半透明系统。粒径为10-100nm，具有很窄的粒径分布。近年来成为药剂学领域的研究热点。     

不同制备条件对阿霉素磁性抗癌毫微粒形貌及粒径大小的影响

本文以反相乳液聚合法制备了阿霉素磁性抗癌毫微粒,并用环境扫描电镜和动态光散射法研究了制备条件时阿霉素磁性毫微粒大小及粒径分布的影响。实验蛄果是,随着引发剂用量增大、反应温度提高,毫微粒粒径先是减小而后增大,并且颗粒间团聚现象变得严重;随着搅拌速度增加,毫微粒粒径逐渐减小,而后变化不大。     

秋水仙碱纳米控释微粒抗肿瘤的实验研究

目的：研究不溶于水的植物性抗癌药秋水仙碱纳米控释静脉注射微粒的制备工艺及其体内外抗肿瘤作用。方法：以聚乳酸－聚乙醇酸共聚物（PLGA）作为基质材料,采用超声乳化－溶剂挥发法制备PLGA包载秋水仙碱的纳米级微粒（NP）。借助扫描电镜观察PLGA－秋水仙碱－NP微粒形态,通过激光光散射实验测定纳米微粒的粒径分布。利用高效液相色谱（HPLC）测定纳米微粒制剂的载药率,以MTT方法做体外杀伤癌细胞实验,进行不同剂量,给药频度条件下体内抑瘤实验。结果：经电镜观察PLGA－秋水仙碱－NP为表现光滑的球形微粒,粒径分布平均值是104．9nm,呈正态分布,PLGA－秋水仙碱－NP载药率为33．0％。体外MTT实验提示纳米粒子粒子与裸药作用相同且显著控释,体内抑制实验表明：控释制剂间隔给药疗效优于包载药物每日给药的疗效,量－效关系, 毒性显著减低,经静脉途径试用无任何不良反应。结论：PLGA纳米粒子可以作为抗肿瘤药物秋水仙碱的有效载体,并可在不添加助溶剂等前提下成功制备其静脉注射剂型,实现药物控制释放并减低毒性,发挥药物更佳的抗肿瘤作用。     

阿柔比星A聚乳酸毫微粒主要性质研究

目的：对载药毫微粒主要质量指标载药量、包封率及其关系,粒径及其分布进行研究,方法：以阿柔比星Ａ聚乳酸微粒为研究对象,以分光光度测定载药量与包封率,以激光粒度分析仪测定粒径及其分布。结果：阿柔比星Ａ聚乳酸毫微粒平均载药量为１８．５％。平均包封率为８６．７％,平均数目径为８０ｎｍ,平均体积径为２３０ｎｍ。结论：载药量与包封率之间具有一定关系。体积径分布是载药毫微粒粒径分布评价不可忽视的内容。     

环孢素脂质体软膏剂制备方法的研究

利用正交设计试验，优选出制备环孢素脂质体（１）的２个最佳处方，制备出１溶液，以显微镜计数法计算其粒径分布，应用薄层色谱分离法半定量地测定了其包封率（２种处方分别为９１．０％、８６．５％）。在此基础上，制备出１外用制剂。并用高效液相色谱法测定了制剂中环孢素的含量     

水相-水相乳化法制备载BSA的葡聚糖微粒

目的采用水相-水相乳化法,制备粒径小且分布集中的载蛋白的葡聚糖（Dx）微粒。方法Dx／聚乙二醇（PEG）双水相系统将蛋白富集于Dx相,两相按比例混匀得PEG包Dx型类乳液。添加海藻酸钠于PEG相作稳定剂,经冻干、除PEG后,得载牛血清白蛋白（BSA）的Dx微粒。采用显微镜及软件分析微粒外观和粒径数据,BCA法测定微粒的包封率和载药量,差示扫描量热器测定微粒及其成分的熔融吸热峰。结果优化的载药微粒圆整均一、平均粒径约5um,载药量、包封率分别在16％、88％以上。结论水相一水相乳化法可制备出粒径小且分布集中、载药性能良好的蛋白-Dx微粒。该法可进一步应用于干粉吸人剂或缓释微球等剂型的研究。     

紫杉醇注射液的制备及其物理稳定性的初步评价

目的制备紫杉醇注射液 ,初步评价其物理稳定性。方法采用混合表面活性剂和混合溶剂对紫杉醇进行增溶 ,制备了紫杉醇注射液。选择适当的等渗液稀释后 ,用激光NICOMP3 80 /ZLS系统测不同时间下相应动态光散射光谱的体积分布频率、散射强度分布频率图谱。结果与结论注射液稀释后的动态光散射光谱 6h内无明显差别 ,粒径大小及分布均符合静脉滴注要求。该制剂制备工艺简单 ,室温放置 1 5a后注射液外观澄清 ,稀释后测定粒径与粒径分布无明显变化 ,物理稳定性良好。     

口服毫微粒的研究进展

毫微粒用于口服具有诸多优点,开发潜力巨大,现已成为药剂学领域的研究热点之一。本文从制备工艺体内摄取与分布、应用等三方面综述了近年来口服毫微粒的最新研究进展,对全面了解和深入研究这类制剂具有一定的意义。     

激光散射法分析异丙酚纳米乳剂的粒径大小与分布

目的制备异丙酚纳米乳剂 ,以激光散射光谱分析其粒径大小与分布 ,为微粒分散药物制剂物理稳定性的研究提供简便、快速、有效的方法。方法制备 3种处方不同 ,工艺相同的异丙酚纳米乳剂 (分别为Ⅰ、Ⅱ及Ⅲ ) ,以激光NICOMP3 80 /ZLS系统测得相应动态光散射光谱的体积为权重的重量平均粒径分布、散射强度为权重的重量平均粒径分布。结果 3个制剂动态光散射光谱有显著差别。纳米乳剂Ⅰ ,两种图谱示单峰 (davg=2 64 2nm) ;纳米乳剂Ⅱ和Ⅲ ,两种图谱示双峰 ,纳米乳剂Ⅱ中大粒子 (davg=3 1 5 5nm)占 5 4 3 % ,而小粒子 (davg=73 6nm)占 45 7% ;纳米乳剂Ⅲ示小粒子 (davg=87 1nm)占 74 9% ,而大粒子 (davg=2 3 2 7nm)占 2 5 1 %。结论 3种纳米乳剂激光光散射光谱有显著差别 ,纳米乳剂Ⅰ粒径与Ⅱ、Ⅲ相比虽稍大 ,但均匀 ,该处方制得的制剂室温放置 3年外观透明 ,物理稳定性良好     

Sizing the optimal dimensions of a vaccine delivery system: a particulate matter

ABSTRACT

Encapsulation of subunit antigens into particulate vaccine delivery systems is a promising strategy to enhance their immunogenicity. The most basic physical parameter of these particles, their size, has a profound effect on the immunogenicity of the vaccine. Interestingly, the optimal particle size varies depending on the desired type of immunological memory and the route of administration. In this editorial, we draw attention to the effect of particle size on the resulting immune response and accentuate the importance of adequate particle sizing methods, within and beyond the intended size range of the delivery vehicle, to assess vaccine quality.     

Dropwise Additive Manufacturing of Pharmaceutical Products Using Particle Suspensions

The principal method of drug delivery is by oral solid doses, the production of which often necessitates multiple post-crystallization unit operations to ensure content uniformity or enhance bioavailability. As an alternative to conventional dose production methods, applications of additive manufacturing technologies based on solvent- or melt-based formulations have demonstrated the potential for improvements to process efficiency, flexibility, and dosing precision. Here we explore the use of particulate suspensions in a dropwise additive manufacturing process as a method for dosing active ingredients in crystalline form, which may be difficult to achieve via powder processing due to poor flow properties. By employing a fluid-based method, powder flow issues are alleviated and adaptation of the process to new particles/crystals is facilitated by dimensional analysis. In this work, a feasibility study was conducted using 4 active ingredient powders, each with non-ideal particle properties, and 2 carrier fluids, in which the active ingredient does not dissolve, to formulate suspensions for dose manufacturing; drug products were analyzed to show reproducibility of dosing and to assess preservation of particle size through the process. Performance across particle types is affected by particle size and shape, and is related through effects on the rheological properties of the formulation.     

Electronic cigarette aerosol particle size distribution measurements

The particle size distribution of aerosols produced by electronic cigarettes was measured in an undiluted state by a spectral transmission procedure and after high dilution with an electrical mobility analyzer. The undiluted e-cigarette aerosols were found to have particle diameters of average mass in the 250–450?nm range and particle number concentrations in the 10⁹ particles/cm³ range. These measurements are comparable to those observed for tobacco burning cigarette smoke in prior studies and also measured in the current study with the spectral transmission method and with the electrical mobility procedure. Total particulate mass for the e-cigarettes calculated from the size distribution parameters measured by spectral transmission were in good agreement with replicate determinations of total particulate mass by gravimetric filter collection. In contrast, average particle diameters determined for e-cigarettes by the electrical mobility method are in the 50?nm range and total particulate masses calculated based on the suggested diameters are orders of magnitude smaller than those determined gravimetrically. This latter discrepancy, and the very small particle diameters observed, are believed to result from almost complete e-cigarette aerosol particle evaporation at the dilution levels and conditions of the electrical mobility analysis. A much smaller degree, ~20% by mass, of apparent particle evaporation was observed for tobacco burning cigarette smoke. The spectral transmission method is validated in the current study against measurements on tobacco burning cigarette smoke, which has been well characterized in prior studies, and is supported as yielding an accurate characterization of the e-cigarette aerosol particle size distribution.     

Lipid nanocapsule size analysis by hydrodynamic chromatography and photon correlation spectroscopy

Particle size and the size distribution are known to be important factors in the overall behavior of nanoparticulate drug delivery systems and an exact determination of these parameters is highly important. Several techniques are applied in the size determination of nanoparticulates, particularly dynamic light scattering. Also other methods have been proposed, among them hydrodynamic chromatography (HDC). In order to characterize a HDC method for nanosized carriers, differently sized lipid nanocapsules having a diameter of 25–100 nm were analyzed and results were compared with measurements from photon correlation spectroscopy (PCS) and atomic force microscopy. Results from atomic force microscopy studies were generally not in line with determinations from the other techniques due to a particle shape loss by the drying step. PCS and HDC led to comparable results in simple size determination of lipid nanocapsules. However, slight differences were found during the characterization of more complex samples. HDC was able to detect micelles as a byproduct of nanocapsule preparation while in PCS the sample dilution turned micelles undetectable. HDC analysis was able to characterize mixed samples of particle batches differing in their average size similar to PCS. HDC was found to be an excellent tool for the determination of size and average size distribution of lipid nanocapsules.     

Response Surface Methodology for the Optimization of Celecoxib Self-microemulsifying Drug delivery System

The aim of the present study was to prepare, evaluate and optimize, self micro emulsifying drug delivery system of celecoxib. A 3 factor, 3 level factorial design was used for the optimization procedure with different amounts of Labrafil 2609 WL, Labrasol, and Cremophor EL as the independent variables. The response variable was selected on particle size (nm) of the droplets after dilution in 0.1N HCl. Particle size of the self micro-emulsifying drug delivery system depends on the quantity of above three independent variables. Three different levels of each independent variable were selected for the optimization. Mathematical equation and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the particle size after dilution was, Particle size (Y)= +27.83+76.07×A-23.62×B-43.83×C+52.72×A(2)+9.82×B(2)+27.20×C(2)-14.52×A×B-32.38×A×C+12.1×B×C, where, A=Labrafil 2609 WL, B= Labrasol, C= Cremophor EL, Y= particle size. The optimized model predicted a particle size of 28.33 nm with 0.16ml of labrafil 2609 WL, 0.17ml Labrasol and 0.22ml of Cremophor EL. The observed response were in close agreement with the predicted values of the optimized formulation. This demonstrates the reliability of the optimization procedure in predicting particle size of self microemulsifying delivery system for celecoxib.     

Influence of particle size on drug delivery to rat alveolar macrophages following pulmonary administration of ciprofloxacin incorporated into liposomes

In order to confirm the efficacy of ciprofloxacin (CPFX) incorporated into liposomes (CPFX–liposomes) for treatment of respiratory intracellular parasite infections, the influence of particle size on drug delivery to rat alveolar macrophages (AMs) following pulmonary administration of CPFX–liposomes was investigated. CPFX–liposomes were prepared with hydrogenated soybean phosphatidylcholine (HSPC), cholesterol (CH) and dicetylphosphate (DCP) in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to five different particle sizes (100, 200, 400, 1000 and 2000 nm). In the pharmacokinetic experiment, the delivery efficiency of CPFX to rat AMs following pulmonary administration of CPFX–liposomes increased with the increase in the particle size over the range 100–1000 nm and became constant at over 1000 nm. The concentrations of CPFX in rat AMs until 24 h after pulmonary administration of CPFX–liposomes with a particle size of 1000 nm were higher than the minimum inhibitory concentration of CPFX against various intracellular parasites. In a cytotoxic test, no release of lactate dehydrogenase (LDH) from rat lung tissues by pulmonary administration of CPFX–liposomes with a particle size of 1000 nm was observed. These findings indicate that efficient delivery of CPFX to AMs by CPFX–liposomes with a particle size of 1000 nm induces an excellent antibacterial effect without any cytotoxic effects on lung tissues. Therefore, CPFX–liposomes may be useful in the development of drug delivery systems for the treatment of respiratory infections caused by intracellular parasites, such as Mycobacterium tuberculosis, Chlamydia pneumoniae and Listeria monocytogenes.     

Particle Engineering for Pulmonary Drug Delivery

With the rapidly growing popularity and sophistication of inhalation therapy, there is an increasing demand for tailor-made inhalable drug particles capable of affording the most efficient delivery to the lungs and the most optimal therapeutic outcomes. To cope with this formulation demand, a wide variety of novel particle technologies have emerged over the past decade. The present review is intended to provide a critical account of the current goals and technologies of particle engineering for the development of pulmonary drug delivery systems. These technologies cover traditional micronization and powder blending, controlled solvent crystallization, spray drying, spray freeze drying, particle formation from liquid dispersion systems, supercritical fluid processing and particle coating. The merits and limitations of these technologies are discussed with reference to their applications to specific drug and/or excipient materials. The regulatory requirements applicable to particulate inhalation products are also reviewed briefly.     

Particle Size and Charge Distribution Analysis of Pharmaceutical Aerosols Generated by Inhalers

Aerosol particles generated by inhalers for respiratory drug delivery acquire electrostatic charge during the dispersion process. The electrostatic charge distribution of the particles can affect the efficiency of drug delivery by influencing both the transport and deposition of inhaled particles in the human lung. To analyze the electrostatic charge acquired by the aerosol particles, two sets of metered-dose inhaler (MDI) and dry powder inhaler (DPI) devices were investigated. Both the particle size and charge distributions were measured simultaneously by using an electrical single-particle aerodynamic relaxation time (E-SPART) analyzer. The analyzer was calibrated with particles of known size, which were generated by a vibrating orifice aerosol generator (TSI Inc.) and charge using the Faraday cup method. The charge distributions of the pharmaceutical aerosols from both the DPI and MDI devices were bipolar in nature. Although the net charge-to-mass ratio was less than 0.2 μC/g, the individual particles were charged with a relatively high charge: ?2 to + 2 μC/g. The count mean aerodynamic diameter of the aerosols generated from these devices was 3–5 μm.     

激光散射法测定阿维A原料药粒度

目的：建立测定阿维A原料药的粒度及其分布的方法。方法：采用Malvern Mastersizer2000激光粒度分析仪、Hydro 2000MU湿法进样器,以《中国药典》粒度和粒度分布测定法中的光散射法进行阿维A原料药的粒度分析并进行方法学考察,泵速为1500r/min,遮光比为5%～15%,背景与样品的扫描时间为5s,样品折射率为1.569,样品吸光率为0.01。结果：方法学考察结果d（0.5）的RSD均〈3%,d（0.1）和d（0.9）的RSD均〈5%;4批阿维A原料药的d（0.1）均小于5μm,d（0.5）均小于10μm,d（0.9）均小于20μm,符合《中国药典》相关要求。结论：该方法简便、准确、重复性好,适用于阿维A原料药的粒度控制。     

Effects of borneol on the pharmacokinetics of 9-nitrocamptothecin encapsulated in PLGA nanoparticles with different size via oral administration

Context: Although nanocarriers provide promising potential for oral drug delivery, the delivery efficiency remains unsatisfactory and needs to be improved. Size is considered to be the most important characteristic of nanoparticles related to their oral absorption. Borneol has been proved to have the ability to enhance the penetration and transport of many drugs through various physical barriers.

Objective: To investigate the effect of the particle size and coadministration of borneol on the pharmacokinetics and bioavailability of entrapped drug in different size poly(lactic-co-glycolic acid) (PLGA) nanoparticles.

Materials and methods: 9-Nitrocamptothecin (9-NC)-loaded PLGA nanoparticles with three different range of size (50–100?nm, 100–200?nm, 200–300?nm) were prepared by emulsion solvent-evaporation method. The pharmacokinetic study in rats of these nanoparticles with borneol was carried out.

Results: The experiments showed that the encapsulation drug in nanoparticles with size below 200?nm could improve the oral bioavailability of 9-NC. The small size nanoparticles (50–100?nm) had a better improvement efficacy. As for borneol, it played a significant promotion effect only on the small nanoparticles. Moreover, there was no significant influence on the nanoparticles with size more than 100?nm.

Discussion and conclusion: The study indicated that both entrapping drug in nanoparticles with the size below 100?nm and coadministrating with borneol could enhance the gastrointestinal absorption of water insoluble drug. The combination of the two strategies provides a potential approach to improve the oral bioavailability of drug.