Tableting of coated particles. I. Small particle size chitosan as an agent protecting coating membrane from mechanical damage of compression force

Formulation of sustained release tablets containing coated particles whose coating membrane is not damaged during compression was studied and several kinds of chitosan of different particle size were evaluated as protective agents for the membrane. Comparison was made with the dissolution rate of the coated particles. Ethylcellulose or ethylcellulose/hydroxypropylcellulose was chosen as a coating agent. When the coated particles were compressed with the small particle size chitosan (Marine Chito), the coating membrane was not ruptured, and the protective effect was not influenced by the compression pressure. Both the Eudragit RS-coated particles and the tablets manufactured by compressing the coated particles with Marine Chito were orally administered to dogs, and the plasma theophylline levels of the two dosage forms were compared to determine the drug release characteristics in the gastrointestinal tract. It was found that the plasma concentration-time curve of the tablets coincided with that of the coated particles, and the compressed tablet would disintegrate instantly and redisperse into many particles in the body after oral administration.     

Preparation and evaluation of slow-release pan-coated indomethacin granules

Granules containing indomethacin crystals are coated with Eudragit solutions of different RL/RS ratios using a pan coating technique. The process is reproducible with regard to drug content, inexpensive and the formed granules were directly compressed into tablets. In vitro release of indomethacin from coated granules, tablets and capsules was studied as a function of different ratios of Eudragit RL/RS in the coating solution. The release of the drug was significantly reduced by the coating process in comparison with a formulation made from uncoated granules, prepared using 10 per cent gelatin solution as a binder. Release data were found to follow a diffusion-controlled model.     

Peroral sustained-release film-coated pellets as a means to overcome physicochemical and biological drug-related problems. I. In vitro development and evaluation

In vitro preformulation testing has shown that the solubility and dissolution rate of the model drug compound ucb 11056 are highly pH dependent. Considering this, different sustained-release (SR) oral dosage forms of ucb 11056 were developed aiming to obtain the most constant and complete release of the drug during transit in the gastrointestinal (GI) tract. Classical approaches based on the use of SR formulations such as hydrophilic matrix tablets or pellets coated with one film-forming polymer (Eudragit NE30D or L30D-55) did not fulfill all expectations on the basis of their in vitro evaluation, i.e., the drug release and pattern remained highly dependent on the pH of the dissolution medium. Therefore, taking advantage of the flexibility of release adjustment obtainable from coating of pellets with different kinds of pH-sensitive film layers, a quite satisfactory pH independence of the release characteristics was obtained using formulation blends of neutral and anionic acrylic polymers. For the selected SR pellets batch 15 coated with NE30D/L30D-55 (7:3), the tridimensional topographic representation of the drug release versus time and pH showed that, notwithstanding the pH-dependent aqueous solubility of the drug, the release profiles were relatively homogeneous for any pH value ranging between 1 and 7.     

Production of bronze powders by water jet cooled rotating disc atomisation

Abstract

New type of water jet cooled rotating disc atomisation unit was designed and constructed. The raw material was melted in graphite crucible with high frequency induction heating, and atomisation was performed in high purity argon gas atmosphere. Cu–10Sn alloy was atomised to investigate the effect of production parameters, such as disc speed, disc surface condition, liquid metal flowrate, disc fin number and superheat of liquid metal with respect to mean particle size and powder yield rate. The produced powders appeared spherical, rounded, ligamentous, irregular and flaky, depending on particle size. The mean particle size of produced powders was in the range of 100–250 μm with 65–85% powder yield rate depending of atomisation parameters. The ZrO₂ material coated disc with four fins gave the finer mean particle size and higher powder yield rate in comparison with uncoated disc with two fins.     

Fabrication of multiunit controlled-release phenylpropanolamine hydrochloride tablets

Phenylpropanolamine hydrochloride (PPA) pellets were prepared in a fluidized-bed rotary granulator. Microcrystalline cellulose and distilled water were used as pelletization enhancer and binder, respectively. The pellets were coated with methacrylate ester copolymer (Eudragit RS 100) solution containing a 1:1 ratio mixture of triethyl citrate and castor oil as plasticizers. The addition of approximately 30% microcrystalline cellulose and 2% croscarmellose sodium to the 50% coated pellets produced fast disintegrating tablets. Dissolution profiles of both pellets and their respective matrix tablets were comparable and conformed to the USP dissolution requirement for PPA extended-release capsules.     

去除废旧硬质合金表面TiN涂层的双氧水+草酸钾碱溶液配制研究

以废旧涂层硬质合金为实验材料,采用双氧水+草酸钾碱溶液去除硬质合金表面TiN涂层,研究了双氧水浓度、草酸钾浓度、pH值和反应时间等对TiN涂层去除效果的影响,得到了草酸钾和双氧水碱溶液的最佳配比,可以为工业生产提供参考。     

Engineering the C-terminus of firefly luciferase as an indicator of covalent modification of proteins

Ketoprofen (Ket), a non-steroidal anti-inflammatory drug, has been incorporated into polymeric micromatrices (microspheres) prepared by a spray drying process and made of cellulose acetate trimellitate (CAT)/ethylcellulose (EC) blends. Drug loaded microspheres were obtained by spray-drying organic solutions of the two polymers and the drug. Characterization of the microparticles (morphology, particle size distribution, drug content, yield of production, surface properties, solvent residues) was carried out and in-vitro release behaviour measured. The release rate of the drug diminished as the proportion of EC was raised.     

Importance of dissolution process on systemic availability of drugs delivered by colon delivery system

The relationship between in vitro drug release characteristics from colon delivery systems and in vivo drug absorption was investigated using three kinds of delayed-release systems. 5-aminosalicylic acid (5-ASA), tegafur (FT) and carbamazepine (CBZ) were selected as model drugs. Pressure-controlled colon delivery capsules (PCC) for liquid preparations, time-controlled colon delivery capsules (TCC) for liquid and solid preparations and Eudragit S coated tablets for solid preparations were used in this study. At first, in vitro dissolution tests for all preparations were performed. Drug release from solid preparations was delayed compared to that from liquid preparations with all three drugs. Next, these preparations were administered to fasted beagle dogs. For 5-ASA, the mean Cmaxs (peak level) of Eudragit S coated tablets and PCC were 5.52 and 16.89 micrograms ml-1, respectively. The mean Tmaxs (time when drug reached peak level) were 3.0 and 5.3 h. AUCs were 22.57 and 48.09 micrograms.h ml-1, respectively. For FT, Cmaxs of Eudragit S coated tablet and PCC were 0.87 and 1.46 micrograms ml-1, and Tmaxs were 7.0 and 6.7 h, respectively. AUCs were 9.73 and 15.55 micrograms.h ml-1 and bioavailabilities were 43.79 and 70.84%. For CBZ, the mean Cmaxs of liquid preparations and solid preparations were 0.37 and 0.22 micrograms ml-1, respectively. The mean Tmaxs were 4.7 and 4.3 h. AUCs were 0.673 and 0.392 micrograms.h ml-1. With liquid preparations, drug was thought to contact to the colonic membrane easily because of lack of interference by stools, and to be absorbed well as compared with solid preparations. From these findings, drug release from colon delivery systems and drug dissolution in the colonic lumen are very important factors for the systemic availability of drugs from the colon delivery systems.     

Using unenhanced helical CT with enteric contrast material for suspected appendicitis in patients treated at a community hospital

OBJECTIVE: We evaluated the accuracy of unenhanced helical CT with enteric contrast material in the diagnosis of appendicitis in children and adults treated at a community hospital. SUBJECTS AND METHODS: Over an 8-month period, 100 consecutive patients with right lower quadrant pain and suspected appendicitis were prospectively evaluated. Thin-collimation helical CT scanning was performed after administration of enteric contrast material. CT interpretations were correlated with surgical pathology (45 patients) and clinical follow-up (55 patients). RESULTS: The findings of 33 CT scans were interpreted as positive for appendicitis (29 true-positives and four false-positives), and the findings of 67 were interpreted as negative for appendicitis (66 true-negatives and one false-negative). Sensitivity was 97%, specificity was 94%, accuracy was 95%, positive predictive value was 88%, and negative predictive value was 99%. In the 67 CT scans with negative findings for appendicitis, an alternative diagnosis was made for 36 patients (54%). CONCLUSION: Unenhanced helical CT with enteric contrast material for the evaluation of appendicitis can be implemented in a community hospital. In our study, such imaging achieved excellent accuracy.     

共沉淀反应条件与分散剂对Cu-Al_2O_3粉末性能的影响

以酸碱含铜刻蚀废液为原料,聚乙烯醇(PVA)为分散剂,并采用添加可溶性铝盐络合共沉淀的方法制备了含铝铜的前驱体粉末,最终采用高温煅烧-氢气还原工艺制备了纳米Al_2O_3弥散强化铜粉末。采用激光粒度仪、SEM-EDS、XRD等研究了络合共沉淀过程中工艺参数对弥散铜粉末及Al_2O_3弥散相粒度的影响。结果表明:通过控制络合共沉淀过程中的反应条件,可制备出粒度小于1.5μm且分布较窄的纳米Al_2O_3弥散强化铜粉末,最佳工艺参数为:母液浓度1.0 mol/L,沉淀氨水浓度20%(体积分数),反应温度70℃,p H值为7;调节分散剂的含量可控制弥散相的粒度及分布,PVA与铜离子的物质的量比为0.4∶1.0时,制备出的纳米Al_2O_3弥散相粒度小于100 nm,粒子间距100~200 nm;粉末经氢气烧结950℃保温60 min,烧结试样的密度为8.45 g/cm~3,硬度为115 HB。     

Bean Dwarf mosaic geminivirus movement proteins recognize DNA in a form- and size-specific manner

Various ratios of succinic acid to fenoldopam mesylate, ranging from 0:1 to 18:1 were incorporated in pellets and coated with 1.5-12% w/w Surelease. Even though the coating level did influence the rate and amount of fenoldopam release, the influence of the succinic acid to drug ratio was much more important and evident at all coating levels. Being a weakly basic drug, fenoldopam release ceased when testing in SIF for succinic acid to drug ratios of 0:1-4:1, with the end of release being more abrupt for the 0:1 than for the 4:1 ratio. Only for a succinic acid to drug ratio of > or =5 was fenoldopam release constant for 6-8 h and independent of the pH-value of dissolution media. For a thin coat of about 2.5% w/w Surelease, those pellets showed an ideal controlled release behaviour with release rates of about 5-10%/h and a total release of almost 80% in 8 h. The dissolution profiles of Surelease coated pellets with high succinic acid to drug ratios (> or =5) and different coating levels, were evaluated for best fits to commonly used kinetic models. Sustained release mechanisms are discussed according to best fit models. The quantification of the pH-adjuster succinic acid, released from pellets with an acid to drug ratio of < or =1 showed, that despite their failure as a controlled release system for fenoldopam, the investigated coats could control the release of succinic acid effectively at optimized coating levels. For increasing succinic acid to drug ratios (< or =4) succinic acid was released at an ever more constant rate and release rates, though still faster than the release rates of fenoldopam, decreased steadily for increasing ratios. At a 5:1 ratio finally release rates of succinic acid and fenoldopam were almost identical. Therefore those pellet cores were almost completely emptied during dissolution testing, with both fenoldopam and succinic acid leaving at a constant rate and a total release of about 80% each for a 2.5% Surelease coat, while lower succinic acid to drug ratios had failed to show any sustained release for such thin Surelease coats. A similar formulation with fumaric acid instead of succinic acid failed to show the desired release pattern, indicating that it is the presence of a sufficiently high amount of succinic acid rather than the presence of an acidic compound in general, that ensures fenoldopam solubility at higher pH-values.     

Slow release from a coated sphere with a slightly deformed coating

Effects of a slight deformation of the coating film on the concentration distribution and the slow release characteristics of a coated drug particle is theoretically investigated in this work. A perturbation technique is employed for transformation of the deformed spherical problem into a series of concentric spherical problems with the degree of deformation considered as the perturbation parameter. In addition, the governing equations are solved analytically by further restricting the deformation shape function. Results in this study indicate that if the deformation is slight or only the average release rate is of interest, the effects of coating shape deformation are secondary. However, if the deformation is not so small and if the drug diffusivity in the film is low, the shape deformation could have a significant effect on the concentration profiles and/or the release rate from different parts of the particle surface.     

Preparation and in vitro dissolution profile of dual polymer (Eudragit RS100 and RL100) microparticles of diltiazem hydrochloride

A microparticulate dosage form for a highly soluble drug, diltiazem hydrochloride, was formulated with Eudragit RS100 and RL100 using a novel dual polymer technique. A mixture of diltiazem with Eudragit RS100 (low water permeability) in acetone was coacervated into soft polymer microdrops, following which a mixture of diltiazem and RL100 (high water permeability) was added to produce microparticles consisting of both polymers with diltiazem dispersed in the matrix. A second formulation was developed using the same method except using Eudragit RS100 for both steps. For a comparative study, diltiazem, Eudragit RS100 and RL100 were combined together in a single matrix and formulated into microparticles. In vitro drug release profiles using USP paddle dissolution apparatus 2 revealed that dual polymer matrix microparticles containing Eudragit RS100 in the inner and Eudragit RL100 in the outer core exhibit a suitable release profile with an initial release of the drug followed by a plateau level for the test period of 5 h. Differential scanning calorimetric analysis showed no interaction of the drug with the polymers.     

Physicomechanical properties of a composite material based on ultrahigh-molecular-weight polyethylene filled with ceramic particles

The effect of the shape of filler particles on the mechanical properties of a composite material based on ultrahigh-molecular-weight polyethylene produced by thermal compacting after preliminary mechanical activation of the initial materials is studied. As a filler, Al₂O₃ in the form of an ultradispersed powder with a particle size of 200 nm or as 1-??m microspheres is used. The effects of the fillers of both types on the mechanical properties of the composite material is found to be positive and comparable in the concentration range under study (1?C10 wt %). The degree of matrix hardening depends on the shape of filler particles.     

含锌废渣水热硫化浮选回收的工艺研究

以某冶炼废水处理工段所产生的废渣为处理对象,采用水热硫化-浮选工艺对其进行资源化处理.实验首先采用正交实验法对水热硫化的影响因素进行考察,结果认为温度是影响废渣中金属锌（Zn）硫化的主要因素,其次为固液比、反应时间和硫磺添加量.最优水热硫化条件为:硫化时间4 h,温度200 ℃,固液比1∶3,硫磺添加量18 %,在最优条件下废渣中Zn硫化率可以达到90 %以上.后续的浮选考察了粒径、抑制剂（CMC）、浮选温度和浮选pH值对硫化产物可浮性的影响.研究认为温度是影响人造硫化物浮选的主要因素,最优浮选参数为:粒径38 μm、温度 60 ℃、CMC: 200 g/t、pH= 8.最优条件下,一次粗选,精矿Zn品位可达28.8 %,Zn的回收率为55.16 %.      

The luminescence immunoassay S-100: a sensitive test to measure circulating S-100B: its prognostic value in malignant melanoma

In this study we measured S-100B using a recently developed luminometric immunoassay with a detection limit of 0.02 microg l(-1). By measuring serum S-100B concentrations in 58 apparently healthy individuals a reference value of 0.16 microg l(-1) was found. To assess the sensitivity of the assay we measured levels of S-100B protein in the serum of 251 patients with cutaneous malignant melanoma before the start of treatment. Only one of 179 patients with limited disease had a serum concentration higher than the reference value, whereas elevated levels were seen in 79% of patients with metastasized disease. In the latter group the NSE serum concentration was elevated in 42%. Using a receiver operating characteristic (ROC) curve it is shown that S-100B is a significantly better parameter than neuron-specific enolase (NSE) for distinguishing patients with limited disease from those with extensive melanoma. Pretreatment S-100B values were highly predictive for the period of survival. Patients with limited disease have increased risk for early death with increasing levels of S-100B protein. Within the group of patients with positive lymph nodes and/or with distant metastases, elevated S-100B levels strongly identified high-risk patients. Our study indicates that the measurement of S-100B as a tumour marker in the management of patients with cutaneous malignant melanoma has clinical significance.     

硫掺杂偏钛酸粉体的制备

以硫酸钛为原料,采用水解法制备了硫掺杂偏钛酸粉体,采用场发射扫描电镜(FESEM)、激光粒度分析等技术对偏钛酸粉体的形貌及粒度进行了分析.系统研究了硫酸钛溶液浓度、水解温度、pH值对水解率、偏钛酸粉体粒径的影响,研究结果表明:硫酸钛溶液浓度、pH值及水解温度对偏钛酸颗粒粒径及原料水解率具有显著影响.最佳工艺条件为:硫酸钛溶液的质量浓度为65 g/L、水解温度60℃、pH值为7.     

不同复合形式对AlSi／BN粉末及其涂层组织性能的影响

本文通过对两种组元的粒度设计,制备出BN与AlSii团聚、BN包裹AlSi、AlSi包裹BN三种形态的AlSi／BN复合粉末,通过大气等离子喷涂制备AlSi／BN可磨耗封严涂层,对粉末及涂层组织性能的研究结果表明,BN与AlSi团聚复合粉末涂层的BN含量最高,热稳定性最好。AlSi包裹BN复合粉末形成的涂层具有最高的硬度,其BN的损失特性为烧损和冲击型损失。     

Radiation dose perturbation at tissue-titanium dental interfaces in head and neck cancer patients

PURPOSE: To determine the dose perturbation effects at the tissue-metal implant interfaces in head and neck cancer patients treated with 6 MV and 10 MV photon beams. METHODS AND MATERIALS: Phantom measurements were performed to investigate the magnitude of dose perturbation to the tissue adjacent to the titanium alloy implants with (100 mu and 500 mu thick) and without hydroxylapatite (HA) coating. Radiographic and radiochromic films were placed at the upper (and lower) surface of circular metal discs (diameter x thickness: 15 x 3.2, 48 x 3.2, 48 x 3.8 mm2) in a solid water phantom and were exposed perpendicular to radiation beams. The dosimeters were scanned with automatic film scanners. Using a thin-window parallel-plate ion chamber, dose perturbation were measured for a 48 x 3.2 mm2 disc. RESULTS: At the upper surface of the tissue-dental implant interface, the radiographic data indicate that for 15 x 3.2 mm2 uncoated, as well as 100 mu coated discs, dose perturbation is about +22.5% and +20.0% using 6 MV and 10 MV photon beams, respectively. For 48 x 3.2 mm2 discs, these values basically remain the same. However, for 48 x 3.8 mm2 discs, these values increase slightly to about +23.0% and +20.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu coating, dose enhancement is slightly lower than that obtained for uncoated and 100 mu coated discs for each beam energy studied. At the lower interface for 15 x 3.2 mm2 and 48 x 3.2 mm2 uncoated and 100 mu coated discs, dose reduction is similar and is about -13.5% and -9.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.8 mm2 discs, dose reduction is about -14.5% and -10.0% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu coating, the dose reduction were slightly higher than those for uncoated and 100 mu coated discs. CONCLUSIONS: For the beam energies studied, dose enhancement is slightly larger for the lower energy beam. The results of dose perturbation were similar for 100 mu coated and uncoated discs. These results were slightly lower for the 500 mu coated discs but are not clinically significant. The dosimetry results obtained from radiochromic films were similar to the ones obtained from radiographic film. The dose enhancement results obtained from ion chamber dosimetry are higher than those obtained from film dosimetry. The ion chamber data represent the data at "true" tissue-titanium interface, whereas the ones obtained from film dosimetry represent the data at film-titanium interface.     

Preparation of nanoscaled yttrium oxide by citrate precipitation method

The nano-Y_2O_3 was prepared from YCl_3 by the citrate precipitation method. The precursor powders were prepared by 0.1 mol/L YCl_3 solution and 0.1 mol/L hydrochloric acid in the presence of 1% surfactant PEG2000, which was dried via an ethanol azeotropic distillation method. The effects of reaction temperature, precursor concentration, hydrochloric acid concentration, surfactant, and calcination temperature on the mean sizes of nano-Y_2O_3 were studied. It was found that the highest yield of precursor was about 70% at the p H value of 5.0, and the yield decreased rapidly at the p H value below 4 or over 6. The reaction temperature revealed no effect on the size of precursor. The optimized precursor concentration and hydrochloric acid concentration were both 0.1 mol/L. Several typical analytic techniques such as particle size analyzer, X-ray diffraction(XRD), thermogravimetric and differential thermal analyses(TG-DTA) and scanning electron microscopy(SEM) were used to determine the characteristics of the prepared nano powders. Homogeneous torispherical nano-Y_2O_3 with the smallest size(20 nm) could be obtained by calcining the precursor powders at 800 oC for an hour.