Effect of Drug Properties on Physical and Release Characteristics of Eudragit Microspheres Prepared by Spherical Crystallization Technique

Ten compounds having different solubilities and molecular weights were evaluated for incorporation into Eudragit microspheres using the spherical crystallization technique, and the effects of drug-related factors on the properties of Eudragit microspheres were investigated. The entrapment of the active compound within the microspheres was highly dependent on the acidic or basic characteristics of the drug. Structural changes were also observed on the microsphere surface prepared at different pH values. Microspheres prepared with slightly and very slightly soluble drugs such as salicylic acid, naproxen, piroxicam, indomethacin, and methylpred-nisolone indicated controlled-release properties. Generally, drug release from microspheres followed the Fickian diffusion model.     

Influence of Granulating Method on Physical and Mechanical Properties,Compression Behavior,and Compactibility of Lactose and Microcrystalline Cellulose Granules

The physical and mechanical properties of lactose (LC) and microcrystalline cellulose (MCC) granules prepared by various granulating methods were determined, and their effects on the compression and strength of the tablets were examined. From the force-displacement curve obtained in a crushing test on a single granule, all LC granules appeared brittle, and MCC granules were somewhat plastically deformable. Intergranular porosity ε_inter clearly decreased with greater spherical granule shape for both materials. Decrease in intragranular porosity ε_intra enhanced the crushing force of a single granule F_g. Agitating granulation brought about the most compactness and hardness of granules. In granule compression tests, the initial slope of Heckel plots K₁ appeared closely related to ease of filling voids in a granule bed by the slippage or rolling of granules. The reciprocal of the slope in the succeeding step 1/K₂ in compression of MCC granules indicated positive correlation to F_g, while in LC granules, no such obvious relation was evident. 1/K₂ differed only slightly among granulating methods. Tensile strength of tablets T_t obtained by compression of various LC granules was low as a whole and was little influenced by granulating method. For MCC granules, which are plastically deformable, tablet strength greatly depended on granulation. Granules prepared by extruding or dry granulation gave strong tablets. Tablets prepared from granules made by the agitating method showed particularly low T_t. From stereomicroscopic observation, the contact area between granule particles in a tablet appeared smaller; this would explain the decrease in intergranular bond formation.     

Influence of Metronidazole Particle Properties on Granules Prepared in a High-Shear Mixer-Granulator

ABSTRACT

Metronidazole is a good example of high-dose drug substance with poor granulating and tableting properties. Tablets are generally produced by liquid granulation; however, the technological process failure is quite frequent. In order to verify how the metronidazole particle characteristics can influence granule properties, three metronidazole batches differing for crystal habit, mean particle size, BET surface area and wettability were selected, primarily designed according to their different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In the presence of lactose monohydrate and pregelatinized maize starch, respectively as diluent and binder, they were included in a formula for wet granulation in a high-shear mixer-granulator. In order to render the process comparable as far as possible, all parameters and experimental conditions were maintained constant. Four granule batches were obtained: granules from placebo (G-placebo), granules from needle-shaped crystals (G-needle-shaped), granules from stick-shaped crystals (G-stick-shaped), and granules from isodimensional crystals (G-isodimensional). Different granule properties were considered, in particular concerning porosity, friability, loss on drying (LOD), and flowability. In order to study their tabletability and compressibility, the different granules obtained were then compressed in a rotary press. The best tabletability was obtained with the isodimensional batch, while the poorest was exhibited by the stick-shaped one. Differences in tabletability are in good accordance with compressibility results: to a better tabletability corresponds an important granule ability to undergo a volume reduction as a result of an applied pressure. In particular, it was proposed that the greatest compressibility of the G-isodimensional must be related to the greatest granule porosity percentage.     

Aging of Tablets Prepared by Direct Compression of Bases with Different Moisture Content

Abstract

Properties of aged tablets prepared by the wet granulation method were found to be affected by the moisture content of the granules. In this study, the storage-induced changes in hardness, disintegration and drug release were evaluated for tablets made by direct compression of three different bases with different initial moisture content. Tablets with high initial moisture content were found to increase in hardness upon storage. The magnititude of such increase is dependant upon the physical properties of the base and the absolute moisture content. The increase in hardness may increase the disintegration time and decrease drug release. Tablets with low initial moisture content were minimally affected by storage. The gain of moisture by some of these tablets led to enhancement in disintegration and drug release. Among the tablets studied lactose based tablets with different initial moisture content were found to be the most resistant to changes upon storage.     

Electrical Properties of PbSnF4Materials Prepared by Different Methods

Data are presented on the electrical conductivity of fluorine ion conducting PbSnF₄solid electrolytes prepared by different methods—aqueous (precipitation from solution and hydrothermal synthesis) and nonaqueous (melt solidification).     

不同衬底上ZnO薄膜的射频磁控溅射制备及结构

利用射频磁控溅射镀膜的方法,在c面蓝宝石、石英玻璃和载破片衬底上成功制备了ZnO薄膜。用x射线衍射和扫描电子显微镜进行了结构分析并观察了样品的表面形貌。结果表明：制备的ZnO薄膜具有良好的C轴择优取向结晶度,并在石英玻璃和载玻片衬底上的ZnO薄膜表面发现了[101]取向的“米粒状”晶粒。     

Differences in Characteristics of Pellets Prepared by Different Pelletization Methods

Pellets are currently a very popular dosage form for oral application. They can be prepared by several pelletization techniques. Extrusion/spheronization, commonly used in the pharmaceutical industry, and modern agglomeration in a rotoprocessor were the methods chosen for pellet preparation in our study. Theophylline (in 10% to 65% concentration) was the model drug, lactose monohydrate was used as filler, microcrystalline cellulose Avicel® PH 101 was thespheronization enhancer, and the wetting agent was purified water. Both techniques led to the formation of pellets of appropriate shape and mechanical properties. Pellets of a higher density, hardness, lower friability, and slightly slower dissolution profiles were obtained by extrusion/spheronization. This method of pelletization also led to production of particles with narrower size distribution and bigger yield of pellets with the requested size.     

Application of Fluidized Hot-Melt Granulation (FHMG) for the Preparation of Granules for Tableting; Properties of Granules and Tablets Prepared by FHMG

ABSTRACT

The objective of this study was to investigate the properties of granules and tablets prepared by a novel Fluidized Hot-Melt Granulation (FHMG) technique. Macrogol 6000 (polyethylene glycol 6000, PEG 6000), macrogol 20000 (polyethylene glycol 20000, PEG 20000), and glyceryl monostearate (GMS) were used as binders with different levels of viscosity and water solubility. The properties of both granules and tablets were compared with those obtained using the Standard Tablet Formulation (STF, lactose/corn starch/hydroxypropylcellulose/magnesium stearate: 66/30/3.5/0.5) for fluidized-bed granulation, which is widely used for wet granulation. To obtain suitable flowability as granules for tabletting, the content of the melting material should be approximately 10 w/w%. The rate of increase in the mean diameter of the granules during FHMG was affected by both the melting temperature and the viscosity of the melting material used in the granules. The compression properties of granules prepared by FHMG were also investigated, demonstrating that these granules had a high pressure transmittance. The hardness and the disintegration time of tablets obtained from granules prepared by FHMG were influenced by the properties of the melting material, such as its compaction behavior, solubility, and wettability. No significant differences of hardness were observed when compared to STF tablets. Tablets prepared from FHMG granules disintegrated within 15 min, whereas the STF tablets showed faster disintegration. It was also demonstrated that the hardness and disintegration time of tablets prepared from FHMG granules were not affected by the tablet porosity. Therefore, tablets with a constant quality may be obtainable under a wide range of compression forces. The results of this study suggested that FHMG is a useful method of preparing granules for tableting without using any solvents or water.     

不同速率下蜂窝纸板静态压缩特性的试验研究

通过RMT计算机辅助压力自动测试系统对2种蜂窝纸板进行了不同速率下的静态压缩试验,得到了连续静态压缩F-δ、σ-ε特性曲线.试验结果表明:2种速率压缩状态下,蜂窝纸板的静态压缩特性基本一致,出现明显的弹性、弹塑性、塑性和压实变形4个阶段,因此在蜂窝纸板的某些设计与应用场合可采用小速率静态压缩特性代替大速率静态压缩特性,从而使问题简化.     

Effect of Binder Level and Granulating Liquid on Phenylbutazone Pellets Prepared by Extrusion-Spheronization

Abstract

The effects of type and amount of binding agent and different amounts of granulating liquid on the physical properties of uncoated beads of phenylbutazone were investigated. The binders used were polyvinylpyrrolidone (PVP) and gelatin/starch (G/S) at two levels, and each formulation at two percentages of granulating liquid; water/ethanol at 60/40 ratio. The ability of these binders to produce pellets of phenylbutazone by the extrusion-spheronization method was evaluated by two criteria. The first was physical properties such as particle size, yield between 710 and 1400 μm, friability, and density. The other criterion was the drug release profile. Generally 5% of gelatin/starch with 80% of solvent produced more uniform pellets with a narrower particle size range and a high yield of spheres between 710 and 1000 μm. Changing the type of the binder, its percentage, and the amount of granulating liquid had no significant effect on the pellet density. Changing the type of the binder or/and its percentage and also the effect of granulating liquid in combination with the other mentioned variables had significant effects on the friability of the pellets. The results show that the amount of granulating liquid and binder amount have the same influence on the drug release from pellets. A slower release rate was observed with increased amounts of these two variables. These differences in the release profiles were parallel to the differences in hardness and structure of the pellets. The difference between particle diameter and the percentage of drug released within 30 min was significant in all formulations.     

Influence of Annealing on Physical Properties of CdO Thin Films Prepared by SILAR Method

Cadmium oxide (CdO) thin films were prepared by successive ionic layer adsorption and reaction (SILAR) method and annealed at 250-450℃ for 2 h. The prepared films were characterized by X-ray diffraction (XRD), optical spectroscopy, scanning electron microscopy (SEM) and Hall effect measurement. The XRD analysis reveals that the films were polycrystalline with cubic structure. Both crystallinity and the grain size were found to increase with increasing annealing temperature. SEM analysis shows the porous nature of the surface with spherical nanoclusters. Energy dispersive spectroscopic analysis (EDS) confirmed the presence of Cd and O elements without any additional impurities. The films exhibited maximum transmittance (82%-86%) in infra-red (IR) region. Transmittance was found to decrease with increasing annealing temperature and the estimated band gap energy (Eg) was in the range of 2.24-2.44 eV. Hall effect measurement shows an increase in carrier concentration and a decrease in resistivity with increasing annealing temperature. The carrier concentration (N) and resistivity (ρ) of about 1.26×1022 cm-3 and 8.71×10-3Ω cm are achieved for the film annealed at 450℃for 2 h.     

Evaluation of Critical Binder Properties Affecting the Compactibility of Binary Mixtures

The aim of this study was to identify essential physical and mechanical properties of various binders and to investigate their influence on the tensile strength and porosity of tablets made from binary mixtures with sodium bicarbonate. The binders were characterized according to axial and radial tensile strength after compression into tablets, yield pressure and minimum porosity during compression, and elastic recovery after compression. The addition of a binder generally resulted in an increase in the tensile strength and a decrease in the porosity of the sodium bicarbonate tablets. The location of the binder in the voids between the sodium bicarbonate particles thus decreasing the porosity of the tablet seemed to be an important consideration. Consequently, the addition of binders with a low yield pressure value and a relatively small elastic recovery value (e.g., polyethylene glycol 3000 and polyvinylpyrrolidone) resulted in tablets of low porosity and high tensile strength, especially in the axial direction. The tensile strength of the pure binder also seemed to be important, especially for binders with a lower degree of deformability (e.g., microcrystalline cellulose and pregelatinised starch). The results also indicated the value of using both axial and radial tensile strength measurements in assessing the effect of a dry binder and showed that the importance of different binder properties varied according to the direction of the tablet strength measurements. The results demonstrated that the applied characteristics of the binders used in this study may serve as a useful tool in evaluating the effectiveness of binders.     

Effect of TiO2 Films Prepared by Different Methods on the Dye-sensitized Solar Cells' Properties

采用溶胶提拉法、粉末刮涂法以及将两种方法结合的混合涂覆法制备了TiO2薄膜,对不同工艺制备的TiO2薄膜进行了金相观察,并将薄膜组装成电池进行伏安曲线测试.Ⅰ-Ⅴ曲线表明,与溶胶提拉法和粉末刮涂法制备的TiO2薄膜相比,混合涂覆法综合了两者薄膜的结构优点,用此法制备出的TiO2薄膜组装成的染料敏化太阳能电池具有较大的光电流、光电压和最大输出功率.     

Development of Agglomerated Talc. III. Comparisons of the Physical Properties of the Agglomerated Talc Prepared by Three Different Processing Methods

Abstract

Agglomerated talc was prepared by the wet granulation method using a fluidized-bed granulator, a planetary mixer, and a high-speed, high-shear mixer. It was found that agglomerated talc produced by a fluidized-bed granulator is more porous, has a more irregular shape, has a lower bulk density, and has more binder-talc contacts. This higher surface area of binder-talc interface and the highly porous and irregular shape of the agglomerated talc produced by the fluidized- bed granulator result in stronger intergranular bonding. The resultant compact was harder. The compression force-time curve also showed that the time required to increase the upper punch force from 10% to 90% was greater for the compaction of the fluidized-bed granulated talc. The longer exposure to shear forces would enhance plastic flow and facilitate the formation of stronger bonds. Phenylpropanolamine HCl tablets containing 77.5 % agglomerated talc as the diluent were prepared. The properties of the tablet were found to be satisfactory. The agglomerated talc developed may be a promising direct compression diluent.     

Development of Agglomerated Talc. III. Comparisons of the Physical Properties of the Agglomerated Talc Prepared by Three Different Processing Methods

Agglomerated talc was prepared by the wet granulation method using a fluidized-bed granulator, a planetary mixer, and a high-speed, high-shear mixer. It was found that agglomerated talc produced by a fluidized-bed granulator is more porous, has a more irregular shape, has a lower bulk density, and has more binder-talc contacts. This higher surface area of binder-talc interface and the highly porous and irregular shape of the agglomerated talc produced by the fluidized- bed granulator result in stronger intergranular bonding. The resultant compact was harder. The compression force-time curve also showed that the time required to increase the upper punch force from 10% to 90% was greater for the compaction of the fluidized-bed granulated talc. The longer exposure to shear forces would enhance plastic flow and facilitate the formation of stronger bonds. Phenylpropanolamine HCl tablets containing 77.5 % agglomerated talc as the diluent were prepared. The properties of the tablet were found to be satisfactory. The agglomerated talc developed may be a promising direct compression diluent.     

溶胶－凝胶二氧化硅驻极体薄膜的物理化学改性

实验研究了由溶胶－凝胶法制备二氧化硅驻极体薄膜的工艺。用红外透射谱、扫描电子显微镜以及驻极体等温表面电位测量和热刺激放电等实验考察了热处理和化学表面修正两个关键工艺对溶胶－凝胶二氧化硅样品驻极体性能的影响。结果表明经过高温条件下一定时间的热处理和化学表面修正，可以制备出性能优良的驻极体薄膜     

Properties of MgB2 Thin Films Deposited on Different Substrates Prepared by Ex-Situ Annealing Process

MgB₂ thin films were deposited on MgO (100) substrate and r-plane Al₂O₃ $(1\bar{1}02)$ substrate by ex-situ annealing of boron film in magnesium vapor. The thickness of ex-situ annealed MgB₂ films is approximately 600 nm according to data observation by ellipsometer. The magnetic properties of samples were determined using a vibrating sample magnetometer. The magnetic field dependence of the critical current density J _c was calculated from M–H loops and also the magnetic field dependence of F _p was compared for the different temperature ranges from 5 to 25 K. The critical current density J _c was found to be around 1.0×10⁶ A/cm² and 1.7×10⁶ A/cm² in zero field at 5 K for MgB₂ films deposited on MgO and r-plane Al₂O₃ substrates, respectively. It was found that the critical current density of the film deposited on MgO became stronger than that of r-plane Al₂O₃ in the magnetic field. The superconducting transition temperature was determined by ac susceptibility measurement using physical properties measurement system. ac susceptibility measurements for MgB₂ films deposited on MgO and r-plane Al₂O₃ substrates were performed as a function of temperatures at constant frequency and ac field amplitude in the absence of dc bias field. The critical current densities as a function of temperature were estimated from the ac susceptibility data.     

多层叠加蜂窝纸板压缩特性研究

通过RMT计算机辅助压力自动测试系统对多层叠加蜂窝纸板压缩特性进行了理论分析和不同速率下的静态压缩试验研究,得到了二层蜂窝纸板连续静、动态压缩F-δ、σ-ε特性曲线.试验结果表明:在2种速率压缩状态下,二层叠加蜂窝纸板的压缩特性基本一致,曲线明显呈周期性,每个周期都与其中一层的静态压缩特性一致;各层按照屈服强度(即弹性阶段应力峰值)由小到大的顺序依次屈服,经历弹塑性、塑性和压实变形各阶段;曲线中的周期脉动对其缓冲性能将产生不利影响,应加以注意.     

不同加载方式下隧道爆破振动特征分析

数值模拟是研究爆破过程的一种重要方法,而模拟爆破结果的可靠性依赖于爆破荷载的加载方式。对几种不同爆破加载方式的要求和特点进行了分析。结合许家坪隧道爆破工程实际,运用ANSYS/LSDYNA动力有限元软件,对三种不同加载方式下的隧道开挖爆破进行了数值模拟,并用现场实测结果进行了对比分析。结果表明:共用节点算法与实测结果最为接近,但计算时间较长,对工程实际中的多炮孔爆破模拟难以实现;炮孔壁上施加三角形荷载与炮孔联心线所在的平面上施加三角形荷载的模拟结果较为接近,两者与实测结果均相差较大,但计算时间及所需内存都较少。对其结果修正后,能达到与实测结果相近的程度。因此,共用节点算法加载方式仅适用于模拟少量炮孔的爆破数值模拟,施加等效荷载方式在模拟实际爆破工程时,适当加以修正,能达到与实际相近的模拟结果。