超临界反溶剂过程制备乙基纤维素超细微粒

超临界反溶剂过程是近年来提出的一种制备纳微米粉体材料的新方法.文中利用超临界反溶剂过程制备乙基纤维素超细微粒.实验以乙醇为有机溶剂,超临界CO2为反溶剂,研究了操作压力、温度、溶液浓度、反溶剂流量等操作参数对制备的超细微粒的形态、粒径及其分布的影响.研究表明,采用乙醇作为有机溶剂可得到较理想的结果,能制备出平均直径在20 nm～40 nm范围内的乙基纤维素超细微粒.通过傅立叶红外光谱分析了乙基纤维素超细微粒结构,从特征基判断其结构未发生变化.     

超临界流体技术制备聚合物超细微粒

以聚甲基丙烯酸甲酯为模型材料,利用近两年提出的超临界流体膨胀减压过程,成功制备出了粒径在5μm以下的超细微粒,系统分析了混合器压力和温度、溶液浓度及进液速率对微粒形态、粒径及其分布的影响。结果表明,混合器压力、溶液浓度和进液速率均对微粒粒径及其分布有明显的影响,而混合器温度的影响较小。较理想的操作条件为混合器压力为10MPa、温度为60℃、溶液浓度为10mg/mL、进液速度为3mL/min。     

超临界抗溶剂技术在制备超细微粒中的应用研究进展

超临界流体抗溶剂技术可以用于制备微细材料,在高分子、医药、电子和化学工业中都具有广阔的应用前景.综述了超临界抗溶剂技术在制备超细微粒方面的应用研究进展.尤其详细介绍了利用超临界抗溶剂技术在制备生物降解聚合物及药物制剂方面的研究现状.     

离子交换树脂法制备氢氧化镍和氧化镍超细微粒

以离子交换树脂为沉淀剂,合成了Ｎｉ（ＯＨ）２和ＮｉＯ超细微粒。初步探讨了合成Ｎｉ（ＯＨ）２的实验条件,研究了不同烧结温度对ＮｉＯ超细微粒晶化过程的影响,用透射电镜和Ｘ射线衍射测得微普的大小、形貌和晶型。     

超细微粒的特性与应用

超细微粒的尺度介于原子、分子与块状物体之间,居于微观粒子与宏观物体交界的过渡区域,称为准零维系统,通常泛指尺度约为1～10nm 之间的微小固体颗粒。从而其特性既非十分微观亦非十分宏观。本文将简洁地介绍它的一些物理、化学特性、磁学与光学特性等。并概要地介绍了超细微粒在各领域中的应用。     

反溶剂法制备肉桂醛/乙基纤维素微胶囊及其表征

采用反溶剂法,以肉桂醛为芯材,乙基纤维素(EC)为壁材制备肉桂醛微胶囊,研究了不同芯壁比对微胶囊包埋率及形貌的影响;采用扫描电镜对所得微胶囊的表面形貌进行观察,借助红外光谱和热重分析等对其形成机理能进行了分析,并对其缓释性进行了测试。结果表明,当芯壁比为1∶3时包埋率最大,达到83%,载药量为21%,微胶囊为分散性好、粒径200 nm~1μm的球形粒子。红外光谱、热重分析结果表明EC可以通过自组装将肉桂醛包裹于其形成的疏水性空腔内部。微胶囊存放7 d后,其中的肉桂醛释放率仅为23%,而肉桂醛混合物中肉桂醛的释放率达到了54%,表明肉桂醛微胶囊具有一定缓释性。     

CoFe2O4超细微粒催化剂的制备,性能与表征

用溶胶－凝胶法制备了钴铁复合氧化物超细微粒催化剂，用ＴＧ－ＤＴＡ、ＴＥＭ、ＸＲＤ等手段考察了加入聚乙二醇２００对其粉体特性及催化性能的影响，结果表明，添加金属量３％的聚乙二醇２００，可显著改善粒子团聚，得到平均粒径为３０ｎｍ、分散均匀的超细粒子，在３５０℃下焙烧２ｈ，可得到前驱体分解完全，非完整晶态的ＣｏＦｅ２Ｏ４，其对对甲酚催化氧化制取对羟基苯甲醛的性能较好。     

Fe—79wt%Ni合金超细微粒的压力效应

用蒸发冷凝法制备了不同平均粒径的Ｆｅ－７９ｗｔ％Ｎｉ合金超细微粒样品。在不同压强Ｐ下，将其压制成圆片及小圆环。随成形压强Ｐ增大，比饱和磁化强度σｓ明显增大，达最大值后，略有减少；矫顽力Ｈｃ呈线性下降。复数磁导率实部μ１及损耗正切ｔｇδ随Ｐ而变化。μ１及ｔｇδ的压力效应与平均粒径ｄ＾－密切相关。     

压力对Fe—29wt%Ni合金超细微粒特性的影响

利用蒸发冷凝法，制备了不同平均粒径的Ｆｅ－２９ｗｔ％Ｎｉ合金超细微粒。在不同压强下，将超细微粒压制成片。随压强增大，马氏体体积分数和比饱和磁化强度σｓ明显增大，而矫顽力Ｈｃ呈线性下降，压力效应与平均粒径ｄ大小密切相关。     

Fe—29wt%Ni合金超细微粒中马氏体转变热效应研究

在Ｎ２气氛中，用蒸发冷凝法，制备了不同平均粒径（１２￣１００ｎｍ）的Ｆｅ－２９ｗｔ％／Ｎｉ合金超细微粒样品。它们是马氏体ａ’（ｂｃｃ）和奥氏体ｒ（ｆｃｃ）的混合体。随样品的平均粒径减小，马氏体体积分数明显增加。在加热过程中，随平均粒径减小，ａ’→ｒ逆马氏体转变温度（Ａｓ和Ａｆ）降低，转变温度范围（Ａｓ－Ａｆ）变窄。在冷却过程中（直到７７Ｋ），没有发现ｒ→ａ’马氏体转变。对奥氏体稳定化的原因，进行了     

Development and characterization of gelatin and ethylcellulose microparticles designed as platforms to delivery fluoride

Purpose: To develop and characterize microparticles containing fluoride sources (FS) from sodium fluoride, sodium monofluorophosphate (MFP) or aminofluoride and evaluate their characteristics as fluoride delivery systems.

Methods: Ethylcellulose microparticles containing fluoride (EM) were prepared by emulsification of ethyl acetate dispersion containing polymer and FS (ethylcellulose:FS ratio of 1:0.25 wt/wt) with aqueous external phase containing polysorbate 80 (0.8% vol/vol) using the volume ratio (organic:aqueous) of 1:5. The organic solvent was evaporated; microparticles were collected by centrifuging, washed with deionized water and freeze-dried. Gelatin microparticles containing FS (GM) was obtained by dispersion of the natural polymer in water, adding FS (6:1 wt/wt) and 20% (wt/wt) of mannitol. The final dispersions were spray-dried. Particle morphology and size were investigated using optical microscopy. The content of fluoride ions in the microparticles was quantified using a potentiometric method. The encapsulation efficiency and in vitro release profile of fluoride was also determined.

Results: Microparticles exhibited polydispersity and mean diameters <145.35 and <124.22 µm for EM and GM, respectively. Considering the entrapment efficiency, the spray-drying technique exhibited greater values than microencapsulation by emulsification and solvent evaporation. The release profile of fluoride ions from microparticles was shown to be modified, fitted first order and guided by Fickian diffusion.

Conclusions: Microparticles prepared with ethylcellulose or gelatin can be used as platform for oral delivery of fluoride, providing a means to increase the local supply of this ion in a controlled manner, providing an increased protection against caries. Moreover, further investigations are needed to demonstrate this property in vivo.     

Physicochemical stability,pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process

Aim: To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process.

Methods: Physicochemical stability was performed in accelerated (40°C 70?±?5% RH) and stress (60°C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.v. administration of PTX equivalent to 6 and 12?mg/kg formulations.

Results: Physical stability of PSD showed excellent stability with no recrystallization of the amorphous form. Chemical stability of PSD in terms of % PTX remaining was 98.2?±?0.6% at 6 months and 97.9?±?0.3% at 4 weeks of accelerated and stress conditions, respectively. The PK study showed a nonlinear increase in AUC with increasing dose, that is, 100% increase in dose (from 6 to 12?mg/kg) resulted in 405.90% increase in AUC. Unlike PK study, the organ distribution study of PTX from PSD showed linear relationship with dose escalation. The order of organ distribution of PTX from highest to lowest for both PSD and Taxol^® was liver>kidney>lung>brain.

Conclusions: This study demonstrated excellent physicochemical stability with insight information on the PK and biodistribution of PTX from PSD prepared by SAS process.     

Preparation of theophylline-hydroxypropylmethylcellulose matrices using supercritical antisolvent precipitation: a preliminary study

Several controlled release systems of drugs have been elaborated using a supercritical fluid process. Indeed, recent techniques using a supercritical fluid as a solvent or as an antisolvent are considered to be useful alternatives to produce fine powders. In this preliminary study, the effect of Supercritical Anti Solvent process (SAS) on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC) was investigated. Two grades of HPMC (HPMC E5 and K100) as carriers were considered in order to prepare a sustained delivery system for theophylline which was used as a model drug. The characterization of the drug before and after SAS treatment, and the coprecipitates with carriers, was performed by X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The dissolution rate of theophylline, theophylline-coprecipitates, and matricial tablets prepared with coprecipitates were determined. The physical characterizations revealed a substantial correspondence of the drug solid state before and after supercritical fluid treatment while drug-polymer interactions in the SAS-coprecipitates were attested. The dissolution studies of the matrices prepared compressing the coprecipitated systems showed that the matrices based on HPMC K100 were able to promote a sustained release of the drug. Further, this advantageous dissolution performance was found to be substantially independent of the pH of the medium. The comparison with the matrices prepared with untreated substances demonstrated that matrices obtained with SAS technique can provide a slower theophylline release rate. A new mathematical model describing the in vitro dissolution kinetics was proposed and successfully tested on these systems.     

超临界CO2抗溶剂法制备紫杉醇缓释微球

采用超临界流体强制分散溶液技术,以D,L-聚乳酸和D,L-聚乳酸-聚乙二醇共聚物为载体材料,分别制备了紫杉醇缓释微球.通过扫描电镜、激光粒度仪检测微球外形及粒径分布;紫外吸光度法测量其载药量和包封率,恒温振荡透析法检测药物的体外释放性能;MTT法检测载药微球对Hela细胞的抑制作用.实验表明,两种载体的缓释微球球形度均较好,表面光滑,平均粒径较小,且粒径分布较窄.以聚乳酸和共聚物为载体的缓释微球载药量分别为5.4%±0.3%和5.3%±0.4%,包封率分别为51%±3%和45%±3%;药物释放呈缓释模式,共聚物载药微球药物释放速率较快.MTT法检测结果表明,载药微球对Hela细胞的增殖有明显抑制,共聚物载药微球对细胞增殖抑制更为明显.     

Supercritical Antisolvent Precipitation of Ethyl Cellulose

Supercritical antisolvent (SAS) technique is an appropriate process to obtain micro- and nanoparticles. The application of this process has, until now, been explored in a variety of different fields including: explosives, polymers, pharmaceutical compounds, colouring matter, superconductors, catalysts, and inorganic compounds. Biocompatible and biodegradable polymers are playing more and more important roles in pharmaceutical areas such as tissue engineering and drug delivery. Formulation of these polymers into suitable solid-state forms plays an important role in safety, stability, and efficiency of the products. Ethyl cellulose is commonly used as drug carrier in controlled delivery systems. In this work, particles of ethyl cellulose have been precipitated by SAS using CO₂ as antisolvent and dichloromethane (DCM) as solvent. We studied the effects of concentration on the particle size distribution (PSD) of the precipitates. Ethyl cellulose size-controlled particles have been produced in the micrometer range 3.8–5.0 μm, and an increase of the mean particle diameter (MPD) was observed with the increase of the concentration of the solution.     

Formulation and characterization of ethylcellulose microparticles containing .l-alanyl- l-glutamine peptide

Context: The l-alanyl-l-glutamine peptide (AGP) has been effective to promote acute glycemia recovery during long-term insulin-induced hypoglycemia (IIH), and the oral administration of AGP is suggested to prevent prolonged hypoglycemia, such as nocturnal hypoglycemia.

Objective: Considering the ability of AGP on glycemia recovery and AGP’s fast metabolism, the aim of current study was to obtain and characterize ethylcellulose microparticles to deliver the drug for a prolonged time.

Materials and Methods: Microparticles were prepared by simple and double emulsification/hardening method and characterized by scanning electron microscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) and FT-Raman spectroscopy and in vitro release.

Results and Discussion: Spherical structures with a mean diameter between 9.30?µm and 13.19?µm were formed. TG analysis showed that the thermal stability of AGP was even more increased by encapsulation with ethylcellulose. In addition, TG, DSC, FTIR and FT-Raman analyses proved that AGP was encapsulated in a molecular way. Higher values of encapsulation efficiency were observed for the microparticles prepared by double emulsification (57.83–83.67%) than for those prepared by simple emulsification (18.37%). However, the last ones could release the peptide in a quicker and more extensive manner than those prepared by double emulsification.

Conclusion: For the first time, microparticles containing AGP were developed and exhibited prolonged in vitro release as well as protection to the drug, and it could be considered as a dosage form for patients who suffer from insulin-induced hypoglycemia and/or nocturnal hypoglycemia.     

CO_2辅助膨胀制备微细PCL颗粒

采用超临界CO_2辅助膨胀结合喷嘴雾化分散过程,制备可用于药物缓控释制剂材料聚己酸内酯微细颗粒。实验考察了聚己酸内酯-二氯己烷溶液浓度、流量、预膨胀温度、顸膨胀压力对颗粒尺寸和形貌的影响。结果表明,增加预膨胀压力、降低预膨胀温度、减小喷嘴孔径能得到聚己内酯微细颗粒;在一定的溶液初始浓度、溶液流率范围内,较高的溶液初始浓度、较高的溶液流率,可得到小于1μm聚己酸内酯微细球状颗粒。     

Preparation and physicochemical characterization of soy isoflavone (SIF) nanoparticles by a liquid antisolvent precipitation method

Soy isoflavone (SIF) nanoparticles were prepared using dimethyl sulfoxide as a solvent and water as an antisolvent. Response surface methodology was used to analyse the influences of several process parameters on the mass median diameter (D50). The SIF concentration (20–40 mg/mL), volume ratio of antisolvent to solvent (5–7 mL/mL), stirring speed (800–1600 r/min), and reaction time (2–4 min) were optimized. The optimal conditions were determined to be a SIF concentration, volume ratio of antisolvent to solvent, stirring speed and reaction time of 29 mg/mL, 7 mL/mL, 1533 r/min and 3 min, respectively. Satisfactory D50 of SIF (101.24 ± 12.21 nm) were achieved. The processed and unprocessed SIFs were tested and characterized. By comparing the parameters, the chemical properties of the processed and unprocessed SIFs did not change, but the water dissolution rate of the prepared SIF nanoparticles was greatly enhanced.     

Preparation of drug nanocrystals embedded in mannitol microcrystals via liquid antisolvent precipitation followed by immediate (on-line) spray drying

The aim of this study is to investigate the feasibility of producing pharmaceutical nanoformulations for enhanced oral or pulmonary delivery of poorly water-soluble drugs via liquid antisolvent precipitation followed by immediate (on-line) spray drying. A poorly water-soluble corticosteroid, budesonide, was chosen as the model drug. Budesonide nanoparticles were prepared through liquid antisolvent precipitation, and then processed into a powdered nanoformulation which consists of budesonide nanoparticles embedded in mannitol microcrystals by immediate (on-line) spray drying. The size of the freshly precipitated and the reconstituted budesonide particles was analyzed by dynamic light scattering (DLS). The spray-dried nanoformulation, together with budesonide and mannitol raw materials, their physical mixture and the spray-dried mannitol, were characterized by field emission scanning electron microscopy (FESEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). In vitro dissolution test and aerosol deposition study were conducted on the spray-dried nanoformulation and the physical mixture of budesonide and mannitol raw materials. It was found that the spray-dried nanoformulation, consisting of mannitol microcrystals comprising budesonide nanocrystals with z-average mean size of 520?±?11.4?nm, exhibited enhanced drug dissolution rate and higher fine particle fraction (FPF). The results of this study indicated the potential of the combined process of liquid antisolvent precipitation followed by immediate (on-line) spray drying to be used as a direct and continuous formulation process to produce powdered nanoformulations to achieve enhanced oral or pulmonary delivery of poorly water-soluble drugs.