Assessment of adhesion and autoadhesion forces between particles and surfaces. Part II. The investigation of adhesion phenomena of Salmeterol Xinafoate and lactose monohydrate particles in particle-on-particle and particle-on-surface contact

The centrifuge technique has been used to compare particle-on-particle and particle-on-surface adhesion with Salmeterol Xinafoate particles on single lactose particles or compacted lactose surfaces. The results from particle-on-particle and particle-on-surface adhesion measurements are not equivalent in terms of median adhesion force. The assessment of adhesion using either particle-on-particle or particle-on-surface systems depends on the process on which information is required: e.g. mixing problems are better investigated by applying the particle-on-particle technique, whereas surface transport problems such as powder compaction or flow can be more appropriately studied using particle-on-surface measurements. Taking autoadhesion measurements from the previous study into account, adhesion and autoadhesion forces were found to allow the prediction and choice of mixture components for powder blends. The results suggest that the homogeneity of such a powder blend depends both on thermodynamic properties and on the adhesion and autoadhesion properties of the single components.     

The relationship between particulate properties of carrier materials and the adhesion force of drug particles in interactive powder mixtures

The influence of particle size, shape, and particle surface roughness of lactose monohydrate carrier particles on the adhesion properties of drug particles in interactive powder mixtures similar in quality of a commercial product (Serevent Diskhaler^®) has been investigated. None of the ten lactose monohydrate batches tested was found to be similar in terms of particle size. To obtain more information about particle shape and surface roughness, mathematical analysis was undertaken to structure the data. The lactose monohydrate batches could be split into four different types of particle shape. In terms of particle surface roughness, as measured by a laser profilometer, three different roughness categories were identified. Two sets of mixtures were prepared to relate the physical properties of the lactose monohydrate particles to the adhesion properties of the drug formulations: (a) constant mixing time and speed (25 min, 42 rpm), and (b) optimal mixing time (speed 42 rpm) to match the adhesion properties of the Serevent Diskhaler^®. All ten lactose monohydrate batches provided different adhesion properties under test condition (a) and the optimum mixing time [test condition (b)] was also different for each batch. Multivariate data analysis showed that the adhesion force between drug and lactose monohydrate increases with a decrease in particle size and for more irregularly shaped, elongated carrier particles. The effect of surface roughness could only be qualitatively assessed and thus no definitive conclusions can be drawn to judge whether adhesion will increase or decrease as surface roughness changes.     

Adhesion force measurement of a DPI size pharmaceutical particle by colloid probe atomic force microscopy

The method to determine the adhesion characteristics of fine drug particles for dry powder inhalation (DPI) was established using a colloid probe which mounted a 1-3 μm drug particle on a commercial atomic force microscope (AFM) cantilever. A new preparation system of colloid probes for fine particles smaller than 2.5 μm in diameter was developed with the aid of a micromanipulator and a video microscope. Using this colloid probe, adhesion force distribution between a spherical polycrystalline drug particle and a plate of lactose monohydrate representing for DPI carrier materials or stainless steel for device wall materials was measured. Atmospheric humidity as well as the material and surface roughness of a target plate affected the determined adhesion force. With increasing surface roughness of a lactose plate, the adhesion force between a drug particle and the plate distributed more widely and their mean value decreased. Adhesion force increased meaningfully with atmospheric humidity. Adhesion force for stainless steel was higher than that for lactose.     

Direct adhesion measurements of pharmaceutical particles to gelatin capsule surfaces

Scanning probe microscopy (SPM) was used to measure directly the adhesion of individual lactose particles to the surface of gelatin capsules employed in dry powder inhalant drug delivery systems. In this study, SPM shows that gelatin capsule surfaces with high surface heterogeneity and high-contrast friction exhibit high adhesion and that gelatin capsule surfaces with low surface heterogeneity and low-contrast friction exhibit low adhesion. The adhesion of lactose particles to gelatin capsules was also determined by measuring the retention of lactose particles in the capsules. The adhesion trend obtained with individual lactose particles using the colloidal probe technique agrees with the macroscopic retention results. The adhesion appears to be proportional to the particle size for homogeneous capsule surfaces. In dry powder inhalation products, the Lifshitz-van der Waals forces and acid-base interactions appear to be the principal forces contributing to particle-surface adhesion. The physicochemical nature of the capsule surface seems to dictate the spatial variation of adhesion across the surface. The SPM results clearly show that the surface physicochemical properties depend on the gelatin and mold release agent utilized in the manufacture of gelatin capsules. One of the practical implications of this study is that extraneous surface contamination of gelatin capsules by chemical processing aids such as mold release agents appears to be a key factor affecting the respirable fraction in dry powder inhalation products.     

Correlation between powder-packing properties and roll press compact heterogeneity

Experimental work was carried out in order to measure the distribution of the effective applied stress in the roll gap during roll press compaction of lactose monohydrate, alumina and sodium chloride. The purpose of the study was to determine the influence of both powder properties and roll press feeding on the compaction. Therefore, a laboratory roll press was specially instrumented. The stress applied on the compact in the roll gap was measured locally by two piezoelectric transducers. The measured stress fluctuated a lot and was not homogeneous along the roll width. This heterogeneity was characterized by measuring the transmission of light through a sodium chloride compact. In fact, the heterogeneity of the compact properties was caused by the heterogeneity of the feeding pressure. The feeding pressure heterogeneity was principally due to the powder packing that took place in the last flight of the screw feeder. The roll press compaction could be very affected by the powder packing especially when small roll presses (pharmaceutical) were used.     

Detachment of polystyrene particles from collector surfaces by surface tension forces induced by air-bubble passage through a parallel plate flow chamber

By allowing an air-bubble to pass through a parallel plate flow chamber with negatively charged, colloidal polystyrene particles adhering to the bottom collector plate of the chamber, the detachment of adhering particles stimulated by surface tension forces induced by the passage of a liquid-air interface was quantified. The detachment forces originating from the passing interface were calculated to range from 10^-9 to 10^-7 N and stimulated detachment of a major proportion of the adhering polystyrene particles, regardless of whether a negatively charged, hydrophilic glass or a hydrophobic, dimethyldichlorosilane-coated glass, or a positively charged, 3-(2-aminoethylamino)propyldimethoxysilane-coated glass collector surface was used. Also, aging of the adhesional bonds between the collector surfaces and the adhering particles up to 72 h or variation of the ionic strength of the particle suspension medium, which was a potassium nitrate solution (10-100 mM), did not prevent detachment of adhering polystyrene particles from the collector surfaces. Assuming that in the case of repulsive electrostatic conditions the polystyrene particles adhered through secondary minimum DLVO interactions, it was calculated that the adhesion force per particle ranged between 10^-14 and 10^-12 N, which is several orders of magnitude insufficient to withstand the detachment force exerted by the passing liquid-air interface. In the case of attractive electrostatic conditions, the DLVO theory does not yield a secondary interaction minimum and an adhesion force was calculated by assuming that the polymer surface structures on the polystyrene particles kept the adhering particles at a distance of 5 nm from the collector surfaces, corresponding to an adhesion force of 10^-11-10^-10 N. Even when the assumption is made that the polystyrene particles can approach the collector surfaces up to the minimal separation distance between two interacting surfaces of 1.57 Å, an adhesion force of 10^-8 N results, which is still of the same order of magnitude as the detachment force originating from the passing liquid-air interface. In summary, this study demonstrates the huge potential of surface tension forces for particle removal and, at the same time, is intended to be a warning for erroneous enumeration of colloidal particles adhering to collector surfaces after 'slight rinsing', 'dipping', or other manipulations said to remove loosely adhering particles.     

Effect of glidants in binary powder mixtures

The intention of this study is to investigate on a particulate level the flow properties of dry powder mixtures consisting of cornstarch and a second nanoscaled material. Special attention is paid to the question on the working mechanism of glidants. In 1974, Rumpf showed that a roughness on the surface of a smooth particle leads to a reduction of its forces of interaction with another particle. The interaction forces are reduced as the surface roughness increases the distance between the centers of gravity of the two interacting particles. Agglomerates as well as the primary particles of materials used as glidants are characterized by diameters in the lower nanometer range. In consequence they are strongly adsorbed at the surface of larger particles and act as a surface roughness. If the effect of a glidant would be due to its ability to act as a surface roughness then all nanoparticles being small enough to reduce the net interaction forces could be used as glidants almost irrespective of their chemical nature. Indeed we have been able to demonstrate that nanoparticles of titanium dioxide, aluminum oxide, silicon dioxide or of carbon black act as glidants. Mixing time directly influences the efficiency of a nanomaterial to act as a glidant. Due to increasing ratio of adhesive force to particle weight with decreasing particle radius, nanomaterials tend to aggregate and agglomerate. With increasing mixing time the size of agglomerates decreases. At the same time the number of primary particles available for adsorption on the surfaces of the cornstarch particles increases. An optimum in flow properties is achieved at a characteristic mixing time. At a further increase in mixing time, the size of agglomerates decreases and the coverage of the cornstarch particles by nanoparticles increases. Eventually cornstarch particles are obtained being completely coated with nanoparticles. The surfaces of these coated particles are smooth. Accordingly they show a poor flow behavior. The property of the nanomaterial to act as a glidant is lost.     

Capillary and van der Waals force between microparticles with different sizes in humid air

It is well known that surface effect forces, such as van der Waals force and capillary force, are the major contributions to adhesion when microsized particles are in contact in humid environment. But it is very complex to calculate the adhesion force between two smooth unequal particles. In conventional approaches, the effective particle radius approximation and the constant half-filling angle assumptions are often used for computing the van der Waals forces between two microparticles. However, the approximation and the assumption are actually difficult to accurately model the forces between unequal particle sizes when the surfaces are with different properties. In this paper, we present a theoretical study of the van der Waals force and capillary force between two microparticles with different radii and the surface properties linked by a liquid bridge. The proposed model provides the adhesion force predictions in good agreement with the previous formula and existing experiment data. Considering the solid particles are partially wetted by the liquid bridge, the van der Waals force is calculated by divided the particle surface into a wetted part and a dry portion in our stimulation. Since the wetted surface portion of the particle is determined by the half-filling angle, the relationship between two half-filling angles of the unequal size particles is developed from the geometrical consideration, which is relate to the size ratio of the particles, the contact angle, and the separation distance. Then, the van der Waals force is determined using the surface element integration. Moreover, the influences of humidity, particles size, contact angle, and separation distance toward the adhesion forces are discussed using the proposed method. Simulations indicate that a higher relative humidity leads to bigger liquid bridges, suggesting a higher capillary force, but at the same time, the van der Waals force decreases due to the decrease in surfaces energy. As for the influence of contact angle, results show that a higher contact angle, that is, a more hydrophobic surface, reduces the capillary force but increases the van der Waals force (absolute value). The simulations also show that the both the capillary force and the van der Waals force (absolute value) increase as the particle size increases. When the particles are separated from each other, the capillary force and van der Waals force decreases gradually. These results are helpful to understand and utilize the adhesion interaction between particles with unequal sizes at the ambient condition.     

A Model for Removal of Compact,Rough, Irregularly Shaped Particles from Surfaces in Turbulent Flows

A model for removal of compact, rough, irregularly shaped particles from surfaces in turbulent flow was developed. Following the approach of our previous bumpy particle model, irregularly shaped particles were modeled as spherical particles with a number of bumps on them. To improve the model, the effect of surface roughness was added to the bumps. Each bump was modeled with large number of asperities and the Johnson-Kendall-Roberts (JKR) adhesion theory was used to model the adhesion and detachment of each bump and asperity in contact with the surface. The total adhesion force for each bump was obtained as the summation of each asperity force in contact with the substrate. To account for the variability observed in the removal of particles, the number of bumps and roughness values of particles are assumed to be random, respectively, with Poisson and log-normal distributions. For particle separation from the surface, the theory of critical moment was used, and the orientation of bumps on the surface was considered when determining the range of shear velocity needed for removal of the irregularly, shaped particles. The effects of particle size, turbulent flow, particle irregularity, and particle surface roughness on detachment and resuspension were studied for different particles and surfaces. Model prediction for removal of rough, irregularly shaped graphite particles from steel substrate was compared with the available experimental data and earlier numerical models, and good agreement was obtained. This study may find application in adhesion and detachment of irregular particles from flooring in indoor and outdoor environments.     

Modeling of continuous self‐classifying spiral jet mills part 1: Model structure and validation using mill experiments

The objective of this work is to develop a milling model for a continuous self‐classifying spiral air jet mill. Its foundation is a population balance model with selection and breakage distribution functions that have been related to a minimal number of mill‐dependent and powder‐dependent parameters. Initially, experimentation is required to determine the mill‐dependent parameters for a specific mill, by milling a “base” powder at multiple operating conditions. Powder‐dependent parameters can be determined from either mill experiments or from material characterization measurements that require small amounts of powder (presented in Part 2). Ultimately, the milling model presented successfully predicts the product particle size using as inputs the feed particle‐size distribution and mill operating conditions. Three crystalline powders, sodium bicarbonate, lactose monohydrate, and sucrose, have been used to test the proposed milling model. © 2014 American Institute of Chemical Engineers AIChE J 60: 4086–4095, 2014     

进料位置与风速对旋风分级器颗粒分级效果的影响

根据旋风分级器内气流速度分布特点进行了进料区域划分,运用非稳态离散相模型和分级实验对比了3个代表性进料位置对颗粒运动轨迹及分级精度的影响,分析了1 μm和10 μm颗粒在不同区域内的受力情况。结果表明,边壁区域进料造成粗组分中细粉夹带现象严重,分级精度差;中部进料区域内流场强度大,粗颗粒受离心力强,细颗粒受轴向气流曳力大,有利于减少颗粒在分级区的停留时间,实现粗、细颗粒的快速分级,对改善分级精度有利;中心位置进料延长了粗颗粒的分级运动路程,增加了粗组分跑损的概率,模拟计算15 μm的粗颗粒进入细组分的质量分数达到11.7%。经实验验证,入口气速在10～22 m·s^-1,中部区域进料时分级后粗、细组分粒度分布曲线重合区面积最小,分级粒径比率值平均提高了25.3%,研究结果为离心气流分级设备的进料位置设计提供了一定的指导。     

Interaction force measurements using atomic force microscopy for characterization and control of adhesion,dispersion and lubrication in particulate systems

Atomic force microscopy is used as a vital tool in understanding the fundamental mechanisms of particulate processes in dry, humid and aqueous systems. Adhesion forces in both dry and humid systems were studied between surfaces of varying roughness, taking into account the capillary forces at high humidity conditions. Colloidal stability in aqueous systems due to non-DLVO forces and steric effects of surfactant aggregates formed on particle surfaces at varying pH and ionic strength conditions were investigated. The force–distance curves obtained by atomic force microscopy were used to determine the mechanical and thermodynamic properties of the self-assembled surfactant structures formed on the surface. Besides determining the repulsive force barrier provided by the surfactant aggregates in dispersion of slurries, the frictional interactions between surfactant adsorbed surfaces were measured using lateral force microscopy, providing valuable insights into the role of dispersants acting as lubricants. The range of interaction forces that can be explored using the Atomic Force Microscopy (AFM) can be utilized to predict, optimize and design a variety of industrially relevant processes such as chemical mechanical polishing (CMP), powder flow and handling and nano-dispersions, just to name a few.     

Direct Evidence of Temperature Variation Within Ceramic Powder Compact During Pulse Electric Current Sintering

Pulse electric current sintering (PECS) is a powerful technique for the preparation of nanoceramics. However, the temperature distribution within the ceramic powder compact during PECS is not uniform. In the present study, aluminum hydroxide powder is used as an in situ temperature indicator to determine the temperature uniformity. The phase evolution within the powder compact is taken to estimate its temperature distribution. The temperature is highest near the top surface of the compact; it then reduces with increasing distance away from the top surface of the compact. The temperature variation can be significantly reduced by inserting a carbon paper in between graphite punches and graphite mold and also by reducing the heating rate.     

Effect of Press-on Forces on Drug Adhesion in Dry Powder Inhaler Formulations

Press-on forces play a major role in dry powder inhaler (DPI) formulations. In this work, we have quantified the press-on forces on different substrates and drugs under controlled conditions. Externally applied forces significantly affect drug adhesion to surfaces and were found to be independent of the type of substrate and drug. A conservative estimate of press-on forces was made and was found to depend inherently on the size and shape of the drug particle and also on the contact area of the drug and substrate. These press-on forces were positively correlated to the mixing energy. It was found to increase quadratically with an increase in mixing speed. This work is of relevance to the pharmaceutical process of mixing DPI formulations, as it relates dispersion performance to the mixing time, batch size and carrier and drug properties.     

Cohesive strength of alumina powder compacts

In order to characterize the nature of the interparticle forces that causes particle agglomeration in submicron size alumina particles, eight commercial alumina powders were investigated. Since the strength of the agglomerates depends upon the interparticle forces and the packing density of the particles the Hartley model which relates the tensile strength, packing density of a powder compact, to the interparticle force has been applied. The present experimental results suggest that in the absence of any electrostatic forces (either force of attraction or repulsion between particles) van der Waals force is responsible for the agglomeration of alumina particles.     

Glass transition and the flowability and caking of powders containing amorphous lactose

Many powders contain amorphous components, such as amorphous lactose in milk powders, which when given sufficient conditions of temperature and water content, will mobilise as a high viscosity flow making the particles sticky. This can lead to increased cohesiveness, powder caking and increased adhesion to surfaces. The transition from the glassy state is established by increasing the powder temperature to above its glass transition temperature which can be measured using differential scanning calorimetry. Exposing milk powder to over 10-20 °C above the lactose glass transition makes the powder more sticky, rendering it a lot more cohesive and also increases its adhesion to a stainless steel surface. This glass transition induced stickiness is time-dependent. Over time, crystallisation can take place converting the amorphous lactose into crystalline lactose. Furthermore, the caking behaviour of powders depends on the amount of component present in the amorphous state. Finally, this work presents an approach for applying the measured relationship between the glass transition and water content for predicting caking problems with powders containing amorphous components.     

Determination of the adhesion force between particles and a flat surface, using the centrifuge technique

By using a centrifuge technique, the influence of powdery material particle size on the adhesion force particle-surface was determined. In order to achieve this, the adhesion of phosphatic rock (ρ_p = 3.090 kg m^− 3) and of manioc starch particles (ρ_p = 1.480 kg m^− 3) on a steel surface were studied. A microcentrifuge that reached a maximum speed rotation of 14000 rpm and which contained specially designed centrifuge tubes was used. There tubes contained the flat surface where the test particles were deposited. The powder particles were dispersed on these disks and the particles detachment were performed using diverse centrifugal speeds. The graphics of particle percentages still adhering on the surface of the disks as a function of the applied detachment force showed that the profile of adhesion force followed a log-normal distribution. The adhesion force increased with particle size. The manioc starch particles presented adhesion forces greater than those for the phosphatic rock particles for all particle sizes studied. The results obtained were compared with the theory proposed by Derjaguin, Muller and Toporov whose theoretical adhesion presented values close to the experimental data for the phosphatic rock particles adhesion on the stainless steel surface. On the contrary, the theoretical values were lower than the experimental ones for the manioc starch particles maybe due to the small roughness of these particles, their physical properties (softer and deformable material) and/or specific chemical interactions since the organic composition of the manioc starch particles that can dominate the adhesion force. Finally, the separation distance among the surfaces in contact (Z₀) was estimated in approximately 1.0 × 10^− 9 m for the phosphatic rock and 5.0 × 10^− 10 m for the manioc starch. These results were weakly dependent on the particle size range.     

反应沉淀法制备超细硫酸沙丁胺醇颗粒及其粉雾剂的表征

The preparation of ultra-fine particles of salbutamol sulphate （SS） was accomplished with a reactive precipitation pathway, in which salbutamol and sulphuric acid were Used as reactants with the solvents of ethanol.The effects of sulphuric acid concentration, reaction temperature, stirring rate, and reaction time onthesize of the particle were investigated. A binary mixture composed of lactose and SS was prepared to evaluate SS. The results showed that ultra-fine SS particles with controlled diameters ranging between 3 μm and 0.8 μm and with a narrow distribution could be achieved. The morphology consisting of clubbed particles wassuccess.fully obtained. The purity of the particles reached above 98% with-UV detection. The dose- of dry powder inhalation was obtained by blending the particles with recrystallized lactose, which acted as a carrier. The deposition quantity of the drug in breathing tract was estimated using a twin imPinger apparatus. Compared with the Shapuer powder （purchased in the market）, the results showed that SS_particles had more quantifies.subsided in simulative lung.. _