Influence of tabletting speed on compactibility and compressibility of two direct compressible powders under high speed compression

To examine the influence of tabletting speed on compactibility and compressibility under high speed compression, two direct compressible powders, alpha-lactose monohydrate and microcrystalline cellulose of different particle size ranges were compressed using an instrumented rotary press with varying tabletting speed and compression force. The maximum applied force and total time during compression (contact time) were determined from a time-force profile, and the relation between these parameters and properties of compacts was examined. For all lactose tablets, the porosity and tensile strength of compacts were less affected by compression rate though they depended on the applied force. However, the properties of microcrystalline cellulose tablets were varied depending on the tabletting speed in addition to the applied force. In an attempt to quantitatively evaluate the effect of compression rate on the compactibility, an empirical equation was derived from the numerical analysis of the experimental data. The compactibility parameters deduced from the equation well elucidated the effect of tabletting speed on the properties of microcrystalline cellulose tablets and lactose tablets made of various particle size powders.     

Mechanical properties and enzymic degradation of thermoplastic and granular sago starch filled poly(ε-caprolactone)

The mechanical, morphological and biodegradation properties of two types of poly(ε-caprolactone)/sago starch (PCL/sago) composites were investigated i.e. dried granulated sago starch and undried thermoplastic sago starch (TPSS). Thermoplastic starch was extruded with a twin screw extruder model Haake Rheomix (TW100 attached to a Haake Rheometer (Haake Rheodrive 5000). The composites were compounded with a Haake internal mixer (Haake Rheomix 3000) attached to the Haake Rheometer. Tensile properties were determined with the Monsanto Tensometer T10. A Shimadzu UV-160A visible UV spectrophotometer was used to monitor the liberation of carbohydrate as a consequence of starch hydrolysis by α-glucoamylase. Determining the weight loss of composites as well as the acid liberated from PCL also monitored biodegradation. The results indicate that dried granulated sago starch function better as fillers in terms of mechanical properties and the ease of biodegradation. However, TPSS imparted better yield strength to the composites. Poor wetting of starch accounts for the decreased mechanical properties at higher starch concentration as agglomeration occurs. While the rigid granular starch retained their shape in the composites, thermoplastic starch that is surrounded by microvoids is easily deformed due to plasticization.     

Sustained-release phenylpropanolamine hydrochloride bilayer caplets containing the hydroxypropylmethylcellulose 2208 matrix. II. Effects of filling order in bilayer compression and manufacturing method of the prolonged-release layer on compactibility of bilayer caplets

The purpose of this study was to establish the manufacturing method of the formulated bilayer caplets containing the hydroxypropylmethylcellulose 2208 (HPMC2208) matrix without lamination. In manufacturing the bilayer caplets containing the HPMC2208 (Metolose 90SH4000) matrix, some bilayer caplets were cracked. We found that cracking of bilayer caplets is not the separation of two layers, but lamination of the prolonged-release layer. It was assumed that Metolose 90SH4000 causes lamination of the prolonged-release layer. Two factors, roller compaction pressure on dry granulation of the prolonged-release layer and filling order of the prolonged-release layer in bilayer compression, were related to lamination of bilayer caplets. The compactibility of the prolonged-release layer decrease with an increase in roller compaction pressure on dry granulation. The compactibility of the prolonged-release layer manufactured by direct compression is superior to that manufactured by dry granulation. The compactibility of the prolonged-release layer in the shape of the second layer, convexo-concave, is superior to that in the shape of the first layer, convexo-convex. This is due to the fact that the density distribution inside the compact in the shape of convexo-concave was more uniform than that in the shape of convexo-convex. The manufacturing method of the formulated bilayer caplets having the prolonged-release layer whose Metolose 90SH4000 content is 60% without lamination is as follows: the prolonged-release layer manufactured by direct compression is fed as the second layer in bilayer compression.     

The relevance of glass transition temperature for the process of tablet formation

The aim was to determine the relevance of the glass transition temperature (T_g) on the compressibility and compactibility of different excipients as celluloses, cellulose derivatives, lactoses, starch, maltodextrin and carrageenan. Their T_g was determined, they were tableted on an instrumented eccentric tableting machine and crushing force was analyzed. Using force, time and displacement tableting behavior was analyzed by 3D modeling. The parameters obtained, d (time plasticity), e (pressure plasticity) and w (fast elastic decompression), show different deformation mechanisms for the materials in relation to their T_g. Further, if the T_g can be reversibly exceeded during tableting, crushing force is high, otherwise crushing force is lower. This revised version was published online in July 2006 with corrections to the Cover Date.     

Determination of rapeseed methyl ester oil volumetric properties in high pressure (0.1 to 350 MPa)

The isothermal compressibility coefficient, the bulk modulus, the cubic expansion coefficient, the density and the propagation speed of the pressure waves of rapeseed methyl ester oil (RMEO) are the thermophysical properties derived from the specific volume determined in this work and compared with the properties of diesel oil (DO). The temperature measurement interval ranges from 288.15 to 328.15 K and the pressure measurement interval from atmospheric pressure to 350 MPa. The experimental method used consisted of a volume change cell characterised by a linear variable differential transformer (LVDT) magnetic induction system adapted to a high-pressure vessel. To calculate the properties the modified Tait-Tammann equation was used and a high correlation coefficient was obtained with a 95% confidence level. The specific volume and compressibility coefficient were greater for DO than for RMEO; also, cubic expansion was greater for DO than for RMEO. These results pave the way for further practical application.     

Calculation of isentropic compressibility and sound velocity in two-phase fluids

Derivative properties from equations of state (EoS) are well defined for homogeneous fluid systems. However, some of these properties, such as isothermal and isentropic (or adiabatic) compressibilities and sound velocity need to be calculated at conditions for which a homogeneous fluid splits into two (or more) phases, liquid or vapor. The isentropic compressibility and sound velocity of thermodynamically equilibrated fluids exhibit important discontinuities at phase boundaries, as noticed long ago by Landau and Lifschitz in the case of pure fluids. In this work, the two-phase isentropic compressibility (or inverse bulk modulus) is expressed in terms of the two-phase isothermal compressibility, two-phase thermal expansivity and an apparent heat capacity, defined as the partial derivative of total enthalpy with respect to temperature at constant pressure and composition. The proposed method is simple (simpler than previous approaches), easy to implement and versatile; it is not EoS-dependent and it requires only a flash routine and the expression of total enthalpy at given pressure, temperature and composition. Our approach is applied to a variety of fluid systems representative of reservoir applications and geophysical situations, including petroleum fluids (oil and gas condensate) and mixtures of water and gas (methane or CO₂). For low gas content in the two-phase fluid, i.e., near bubble point conditions, we obtain significantly lower bulk moduli and sound velocities than predicted within Wood's conventional approach, in which the liquid and gas phases are considered to be “frozen” at the passage of the acoustic wave.     

Bulk Copolymerization of Conjugated Linoleic Acid With Styrene and Butyl Acrylate: Reactivity Ratio Estimation

Free radical bulk copolymerizations of conjugated linoleic acid (CLA)/styrene (Sty) and CLA/butyl acrylate (BA) were performed at 80°C. Copolymers were characterized for composition, conversion, molecular weights and glass transition temperature (T_g). A pseudo-kinetic model was developed and validated with experimental data. Reactivity ratios estimations were performed and one impurity commonly found in CLA, oleic acid, influenced the reaction kinetics significantly. The T_g of CLA homopolymer was predicted to be 5°C.     

Compression of Langmuir films composed of fine particles: collapse mechanism and wettability

The collapse mechanism of microparticulate Langmuir films was studied experimentally in the present work. Using a Wilhelmy film balance, surface pressure vs area isotherms were determined, and the particle removal during the compression was examined by video-microscope and by naked eye. Upon compressing partially wettable 75 microm diameter surface modified glass beads at liquid (water or aqueous surfactant solution)-air (or n-octane) interfaces, different collapse mechanisms were visualized depending on the wettability of the particles. At low contact angles (below 40 degrees ) irreversible particle removal was observed as a consequence of a particulate line-by-line collapse mechanism. At higher contact angles a buckling-type collapse mechanism was revealed without particle removal from the liquid interface. In the case of irreversible particle removal we assessed the contact angles from the nondissipative part of the isotherm. These values were found to be in reasonable agreement with those determined directly on the beads.     

Compressibility study of quaternary phospholipid blend monolayers

The mechanical properties of liposome membranes are strongly dependent on type and ratio of lipid compounds, which can have important role in drug targeting and release processes when liposome is used as drug carrier. In this work we have used Brewster's angle microscopy to monitor the lateral compression process of lipid monolayers containing as helper lipids either distearoyl phosphatidylethanolamine (DSPE) or dioleoyl phophatidylethanolamine (DOPE) molecules on the Langmuir trough. The compressibility coefficient was determined for lipid blend monolayers containing the helper lipids above, cholesterol, distearoyl phosphatidylcholine (DSPC) and pegylated-DSPE at room temperature. Two variables, the cholesterol fraction and the ratio ρ between the helper lipid (either DSPE or DOPE) and the reference lipid DSPC, were studied by multivariate analysis to evaluate their impact on the compressibility coefficient of the monolayers. The cholesterol level was found to be the most significant variable for DSPE blends while the ratio ρ was the most significant one for DOPE blend monolayers. It was also found that these two variables can exhibit positive interaction and the same compressibility value can be obtained with different blend compositions.     

Thermodynamic and structural properties of phospholipid langmuir monolayers on hydrosol surfaces

Measurements of Langmuir pressure/area isotherms, rheology, grazing incidence X-ray diffraction (GIXD), and grazing incidence diffuse X-ray scattering out of the specular plane (GIXOS) have been used to investigate the influence of a hydrosol containing charged mineral nanoparticles on the thermodynamic and structural properties of a DPPC monolayer. The mineral adsorption layer that is formed via electrostatic interaction underneath the lipid layer alters the thermodynamic properties of the phospholipid monolayer in terms of maximal achievable compression, compressibility, and phase behavior. Modifications appear in the latter case as a coolinglike effect. Rheology measurements of the bulk viscoelastic properties revealed a stabilizing effect of the transient bulk network on the surfactant layer. The lipid chain lattice is found to be reorganized and adapted to the internal atomic structure of the mineral particles. A model for the superposition of Bragg rods from the lipid chains and the minerals is applied to separate these scattering contributions. In the vicinity of the mineral particles, the (2) reflection for DPPC on a liquid substrate was found, indicating strongly suppressed fluctuations at the surface. An estimation of the Debye-Waller factor associated with the lipid layer organization is used to quantify the damping of fluctuations within the lipid matrix due to the rigidifying and stabilizing effect of the mineral particles.     

Formation of langmuir-blodgett films containing two-dimensional monoatomic arrays of rare-earth cations

The work is focused on the preparation and characterisation of rare-earth containing stearic acid Langmuir-Blodgett (LB) films. Stearic acid monolayer behavior on the rare-earth containing aqueous subphase have been analyzed by thermodynamic measurements. The compression isotherm shape changed substantially under varying the anion type at the constant rare-earth cation content in aqueous subphase. The structure of formed multilayer rare-earth containing LB films was studied using small angle X-rays diffraction. The considerable structural defects in multilayer films were found when rare-earth chloride solution was exploited as aqueous subphase, caused presumably by electrostatic interactions at the monolayer surface under high binding of rare-earth cations. The use of monodentate complexones like acetic acid was proposed to form bulk phase quasi-neutral rare-earth complexes. The electroneutral ligand exchange reactions of such complexes with stearic acid monolayer allowed to neutralise monolayer surface under rare-earth cations binding and to form condenced monolayer below the triple-point temperature. The compression of such monolayer to the state of minimal compressibility and subsequent monolayer deposition resulted in the formation of high ordered LB films with high content of adsorbed multivalent rare-earth cations arranged in two-dimensional monoatomic arrays.     

Measurements of the thickness compressibility of an n-octadecyltriethoxysilane monolayer self-assembled on mica

The surface forces apparatus technique and the Johnson-Kendall-Roberts theory were used to study the elastic properties of an n-octadecyltriethoxysilane self-assembled monolayer (OTE-SAM) on both untreated and plasma-treated mica. Our aim was to measure the thickness compressibilities of OTE monolayers on untreated and plasma-treated mica and to estimate their surface densities and phase-states from the film compressibility. The compressibility moduli of OTE are (0.96 +/- 0.02) x 10(8) N/m(2) on untreated mica and (1.24 +/- 0.06) x 10(8) N/m(2) on plasma-treated mica. This work suggests that the OTE phase-state is pseudocrystalline. In addition, the results from the compressibility measurements in water vapor suggest that the OTE-SAM on both untreated and plasma-treated mica is not homogeneous but rather contains both crystalline polymerized OTE domains and somewhat hydrophilic gaseous regions.     

Elastic piezoelectric aerogels from isotropic and directionally ice-templated cellulose nanocrystals: comparison of structure and energy harvesting

We report the preparation of highly compressible and elastic piezoelectric aerogels of carboxylated cellulose nanocrystals (CNCs). Aqueous CNC dispersions containing polyethyleneimine and crosslinker were frozen isotropically to yield isotropic aerogels, while oriented aerogels were prepared by directional freezing. These aerogels were highly flexible and porous (~?85% void fraction), exhibiting greater than 90% recovery at 50% compressive strain even after 100 compression–decompression cycles. Since such aerogels with low bulk modulus and high anisotropy would be an ideal platform for leveraging the piezoelectric properties of CNCs, we used them to prepare piezoelectric nanogenerator devices and determined their energy transduction behavior. Anisotropic aerogels led to an enhanced open-circuit voltage of 840 mV (at ~?8 N applied force), which is over 2.6 times higher than isotropic aerogels (320 mV). The energy density of anisotropic aerogels was around 52 nW/cm², representing outstanding piezoelectric performance for cellulose-based aerogels. Such aerogels with high compressibility, elastic recovery and exceptional piezoelectric performance could have potential applications in sensors, wearable electronics, etc.

     

Multiscale surface self-assembly of an amyloid-like peptide

We present the 2D self-assembly properties of an amyloid-like peptide (LSFDNSGAITIG-NH2) (i.e., LSFD) over a whole range of spatial scales. This peptide is known to adopt an amyloid-like behavior in water where it aggregates into fibrils. Monolayers of this 12 amino acid peptide were built by direct spreading and compression of an organic unstructured LSFD solution at the air/water interface. Investigation by infrared spectroscopy of the peptide secondary structure reveals beta-sheet formation at the water surface. As evidenced by Brewster angle microscopy, compression of the peptidic film results in the formation of large condensed domains. We used atomic force microscopy to show that these domains are made of rather monodisperse, elongated domains of monomolecular thickness, which are about 1 microm long and hundred of nanometers wide. These nanodomains can be compacted up to the formation of a homogeneous monolayer on the micrometer scale. These bidimensional structures appear as a surface-induced counterpart of the bulk amyloid fibrils that do not form at the air/water interface. These self-assembled peptide nanostructures are also very promising for building organized nanomaterials.     

On-chip measurements of cell compressibility via acoustic radiation

Measurements of mechanical properties of biological cells are of great importance because changes in these properties can be strongly associated with the progression of cell differentiation and cell diseases. Although state of the art methods, such as atomic force microscopy, optical tweezers and micropipette aspiration, have been widely used to measure the mechanical properties of biological cells, all these methods involve direct contact with the cell and the measurements could be affected by the contact or any local deformation. In addition, all these methods typically deduced the Young's modulus of the cells based on their measurements. Herein, we report a new method for fast and direct measurement of the compressibility or bulk modulus of various cell lines on a microchip. In this method, the whole cell is exposed to acoustic radiation force without any direct contact. The method exploits the formation of an acoustic standing wave within a straight microchannel. When the polystyrene beads and cells are introduced into the channel, the acoustic radiation force moves them to the acoustic pressure node and the movement speed is dependent on the compressibility. By fitting the experimental and theoretical trajectories of the beads and the cells, the compressibility of the cells can be obtained. We find that the compressibility of various cancer cells (MCF-7: 4.22 ± 0.19 × 10(-10) Pa(-1), HEPG2: 4.28 ± 0.12 × 10(-10) Pa(-1), HT-29: 4.04 ± 0.16 × 10(-10) Pa(-1)) is higher than that of normal breast cells (3.77 ± 0.09 × 10(-10) Pa(-1)) and fibroblast cells (3.78 ± 0.17 × 10(-10) Pa(-1)). This work demonstrates a novel acoustic-based method for on-chip measurements of cell compressibility, complementing existing methods for measuring the mechanical properties of biological cells.     

The effect of particle size on hydrolysis reaction rates and rheological properties in cellulosic slurries

The effect of varying initial particle sizes on enzymatic hydrolysis rates and rheological properties of sawdust slurries is investigated. Slurries with four particle size ranges (33 microm < x < or = 75 microm, 150 microm < x < or = 180 microm, 295 microm < x < or = 425 microm, and 590 microm < x < or = 850 microm) were subjected to enzymatic hydrolysis using an enzyme dosage of 15 filter paper units per gram of cellulose at 50 degrees C and 250 rpm in shaker flasks. At lower initial particle sizes, higher enzymatic reaction rates and conversions of cellulose to glucose were observed. After 72 h 50 and 55% more glucose was produced from the smallest size particles than the largest size ones, for initial solids concentration of 10 and 13% (w/w), respectively. The effect of initial particle size on viscosity over a range of shear was also investigated. For equivalent initial solids concentration, smaller particle sizes result in lower viscosities such that at a concentration of 10% (w/w), the viscosity decreased from 3000 cP for 150 microm < x < or = 180 microm particle size slurries to 61.4 cP for 33 microm < x < or = 75 microm particle size slurries. Results indicate particle size reduction may provide a means for reducing the long residence time required for the enzymatic hydrolysis step in the conversion of biomass to ethanol. Furthermore, the corresponding reduction in viscosity may allow for higher solids loading and reduced reactor sizes during large-scale processing.     

胶质液体泡沫的流变性

应用RV-30旋转粘度计和锥板式RS300应力控制流变仪, 采用稳态剪切方法和小振幅振荡剪切对胶质液体泡沫(CLA)体系的流变特性进行了系统分析, 讨论了温度、 相体积比(油相与水相体积比, PVR)和剪切速率对体系流变性质的影响. 稳态剪切实验结果表明, CLA体系表现出非牛顿流体特征, 其流变行为符合Herschel-Bulkley流变模式. 同时, CLA体系表现出剪切稀释特性, 不具有触变性. 粘弹性实验结果表明, 在低PVR(PVR=2~4)条件下, CLA无线性粘弹性区; 当PVR=8时, 表现出一定程度的粘弹性; 温度对体系的流变行为和粘弹性的影响不显著. 通过与高内相乳状液(HIPRE)体系比较, 发现CLA与HIPRE具有相似的流变特性, 这也说明两者在微观结构上具有一定的相似性.     

Development and validation of a spectrophotometric method for the determination of macrolide antibiotics by using 2,4-dinitrophenylhydrazine

A simple, novel, sensitive, and specific spectrophotometric method was developed and validated for the determination of azithromycin (AZ), clarithromycin (CLA), and roxithromycin (ROX) in bulk powders and their dosage forms. The proposed method was based on the interaction of any of the cited drugs with 2,4-dinitrophenylhydrazine in the presence of an acid catalyst, followed by treatment with a methanolic solution of potassium hydroxide; an intensely colored chromogen was formed that was measured in dimethylformamide, as the diluting solvent, at 542-545, 523-526, and 539-542 nm for AZ, CLA, and ROX, respectively. All variables affecting the development of the measured chromogens were studied and optimized. Beer's law was obeyed in the concentration ranges of 5-40, 5-35, and 5-35 microg/mL for AZ, CLA, and ROX, respectively, with good correlation coefficients (0.9991-0.9999). The limits of detection for this method ranged from 0.77 to 1.47 microg/mL, and the relative standard deviations were 1.24-1.8%. The proposed method was applied successfully to the determination of the 3 drugs in pure bulk form, tablets, and suspensions without interference from commonly encountered additives. The results compared favorably with those of a previously reported method. The mechanism of the reaction was also studied.     

Tabletting of solid dispersion particles consisting of indomethacin and porous silica particles

We attempted to make the rapidly dissolving tablet (Tab) containing solid dispersion particles (SD) with indomethacin (IMC) and porous silica (Sylysia350) as carrier prepared by using spray-drying technique. Rapidly dissolving tablet was formulated with mannitol as a diluent and low substituted hydroxypropylcellulose (L-HPC) or partly pre-gelatinized starch (PCS) as a disintegrant. The percent dissolved from Tab (SD) was higher than that of tablet containing physical mixture (PM) at 20 min. Nearly 100% of drug in Tab (SD) was dissolved within 60 min, while the drug dissolution of Tab (PM) was not completed at the same time period. In addition, the tensile strength of Tab (SD) was much higher than that of Tab (PM). Adding L-HPC in Tab (SD) (Tab (SD-L-HPC)), the percent dissolved from Tab (SD-L-HPC) at 5 min became much higher than that from Tab (SD). The dissolution profile of IMC from Tab (SD-L-HPC) was almost the same irrespective of the compression pressure, while the tensile strength of tablet increased with increasing the compression pressure. In comparing the compaction property of these tablets by observing the ratio of residual die wall pressure (RDP) to maximum die wall pressure (MDP) (RDP/MDP), it was found that addition of L-HPC in the tablet formulation improved compactibility. In case that PCS was formulated as disintegrant, Tab (SD-PCS), similar improvement in the dissolution profile and tensile strength was observed, though the dissolution rate of IMC from Tab (SD-PCS) was slightly lower than that from Tab (SD-L-HPC) irrespective of the compression pressure.