Predicting the Performance of Granulation Binders Through Micro‐Mechanistic Observations

The selection of an appropriate polymeric binder to be used to agglomerate drug with excipients is a critical issue for the development of high shear wet granulation processes for pharmaceutical tablet systems. The aim of the study reported here is to determine the potential for successful granulation through measurement of the interactions of two polymer binder solutions, hydroxypropyl methylcellulose (HPMC) and polyvinyl‐pyrrolidone (PVP), with individual paracetamol drug crystals. A novel micro‐force balance (MFB) has been used to measure different parameters of the crystal‐to‐binder interaction, including the forces exerted by axially strained liquid bridges formed between either two paracetamol crystals or between a reservoir of binder solution and a single paracetamol crystal, the paracetamol‐to‐binder wettability, the post rupture volume distribution and the residue deposited on each crystal. Video images of the separation sequences were obtained simultaneously for analysis of bridge geometry, contact angles, volume distribution and binder residues. It was found that the formation of liquid bridges and their ability to bond particles together depends on the amount of binder left on a crystal after contacting a reservoir of binder (for example, large binder drop). Crystals in contact with HPMC were able to retain more liquid from a binder reservoir than those contacted with PVP solutions. This behaviour is seen to be more important to the final granule strength than the liquid binding force holding particles together in the wet agglomerate.     

The basic growth parameters of ZnS single crystals grown by sublimation

The application of the crystal growth dislocation theory [11] to ZnS single-crystal growth is discussed. The experimental material, above all for determining the actual supersaturation in the growth region and the mechanism of ZnS transport (diffusion, transport gas, chemical transport) was found to be insufficient. An expression for the growth rate of the ZnS crystal plane (the dependence on the supersaturation is not linear) is derived and two different stages in growing ZnS crystals are described.     

人工水晶的结晶习性与缺陷

本文从晶体结构入手研究了水晶的结晶习性与生长时物理、化学条件之间的关系,提出三方偏方面体单形在水晶生长过程中具有重要作用的论点。通过对水晶结晶习性的剖析,使表面结构与内部结构得到由表及里的联系。从籽晶取向(z切,y棒,x棒与z轴相交55°切型等)研究了三方偏方面体结晶习性与晶体缺陷之间的关系。结果表明:人工水晶中的缺陷主要是三方偏方面体晶面的生长痕迹,称之为“子面缺陷”;在y棒和x棒晶体中还有各族晶面之间形成的“生长锥界面缺陷”。 关键词：     

Experimental investigation of the adhesive contact of an elastomer

The present work is an experimental study of adhesion between an elastomer and a rigid cylindrical indented The experimental characterization was carried out using a specially developed apparatus. Adhesive force was measured as function of contact geometry, pull-off velocity, normal force, temperature, waiting time, and material properties. Experimental results are compared with existing theoretical models for adhesion of elastic and viscoelastic bodies. Our study shows that the adhesive force between the studied elastomer and a steel cylinder is determined by completely different mechanisms than assumed in the Kendall’s theory. In particular, it does not depend on the surface energy and is almost entirely dominated by the viscosity of the elastomer.     

Effect of mechanical deformations on the growth of crystals (according to atomic force microscopy data)

Nanosized morphological transformations occurring on the surface of a crystal in the area drawn by a probe needle during the growth of a scratch and the growth kinetics of crystals subjected to mechanical impact have been studied by atomic force microscopy (AFM). A series of experiments with mechanical impact on topographically different areas of a growing face (100) of a dioxidine crystal has been performed. It has been shown that even slight local contact between the probe needle and the surface on a nanoscale leads to essential crystallogenetic (morphological and kinetic) consequences, and its effect is perceptible for a long time. Among these consequences are the coarsening of stages, the appearance of great fluctuations in the growth rate of stages, the loss of morphological stability by the surface even at a distance of several tens of micrometers from the contact area, and also the phenomenon of simultaneous growth and dissolution in neighboring areas of stages.     

The formation of a dislocation spiral on the (101) face of a monoclinic lysozyme crystal: High-resolution experiments

The elementary processes of crystal growth in the case of a low kink density on step edges have been studied by in situ atomic force microscopy. High-resolution images of the first turn of the polygonal dislocation spiral on the (101) face of monoclinic lysozyme crystals, which allow one to discern separate crystal cells, have been obtained. It has been shown that the dependence of the spiral segment velocity on its length is inconsistent with the Gibbs-Thomson law and is represented by several rectilinear sections. The results were explained by taking into account the features of the growth of crystals with a low kink density at low supersaturation.     

Ib型金刚石大单晶的限形生长

金刚石的限形生长有利于其后续加工.对于磨料级金刚石限形生长的研究已经比较透彻,但金刚石大单晶的限形生长尚缺乏全面系统的研究.本文以Fe Ni(64wt%:36wt%)合金为触媒,利用高温高压下的温度梯度法在5.6 GPa时对不同温度下分别沿(100)面和(111)面生长的Ib型金刚石大单晶的晶形进行了研究.研究表明:随着温度的升高,沿(100)晶面生长的金刚石大单晶的晶形分别为板状、塔状直至尖塔状,而沿(111)面生长的金刚石大单晶的晶形则分别为塔状和板状;分析了不同温度下分别沿(100)面和(111)面生长金刚石大单晶不同晶形高径比的变化情况.利用不同压力和温度下的金刚石大单晶合成实验绘制了沿(100)和(111)面生长金刚石大单晶的晶形在V形生长区域内的分布示意图,表明沿(111)面生长的金刚石大单晶V形区温度下限明显比以(100)面生长的高,而沿这两面生长金刚石大单晶的V形区温度上限差别并不明显.对不同生长面V形区温度上下限的差别进行了解释,据此实现了Ib型金刚石大单晶的限形生长.     

Effect of ultrasound on sodium arsenate induction time and crystallization property during solution crystallization processes

The effect of ultrasound vibrations on the cooling crystallization of sodium arsenate in supersaturated solutions was investigated. In particular, the effects of ultrasound vibrations on induction time and crystal size distribution were studied using a laser-based apparatus with relative supersaturation ranging from 1.3 to 1.8. The results show that ultrasound vibrations have a significant effect on reducing induction time and crystal size distribution. The application of ultrasound vibrations to the system resulted in a small change in surface tension; however, the induction time and crystal size significantly decreased. The mean size of sodium arsenate crystals decreased from 398.87 ± 3.27 to 168.68 ± 2.07 μm, as the ultrasound power increases from 26 to 130 W. Ultrasound vibrations significantly reduced the induction time in a highly supersaturated solution compared to that in a low supersaturated solution.     

VUV light induced surface interaction and accelerated diffusion of carbon, silicon, oxygen and other contaminants in LiF crystals

One hundred and fifty-seven nanometers irradiation of LiF crystals accelerates the penetration of C, O, N, Si and other contaminants within the crystal bulk. New bonding between the contaminant elements in both the irradiated and the non-irradiated areas of the crystal was identified. The chemical changes eventually form inhomogeneous nano/micro-islands, which further agglomerate to larger structures in the form of an interfacial layer. The concentration and diffusion (∼100 nm) of contaminants in the irradiated part of the crystal is higher than for the non-irradiated one. The accelerated diffusion is due to a force perpendicular to the crystal surface. This force is generated by the laser's electric field gradient in the direction of beam propagation due to the inhomogeneous absorption at the interfacial layer. A theoretical diffusion model in the presence of the laser field allows rationalizing and interpreting the experimental results.     

A phase-field/Monte-Carlo model describing organic crystal growth from solution

In this paper work we present a phase-field/Monte-Carlo hybrid algorithm for the simulation of solutal growth of organic crystals. The algorithm is subsequently used for an investigation of diffusion effects on the growth mechanisms. This method combines a two-scale phase-field model of the liquid phase epitaxial growth and a Monte-Carlo algorithm of the 2D nucleation and thus is faster than previous purely Monte Carlo simulations of crystal growth. The inclusion of supersaturation and diffusion in the method allows the study of crystal growth under various growth conditions. Parameters used in the hybrid algorithm are bound to the energetic parameters of crystal faces, which can be estimated from a detailed study of the actual crystal structure based on a connected nets analysis, which allows the prediction of the shape and morphology of real crystals. The study of the diffusion effect is carried out based on an example of a hydroquinone crystal, which grows from the water solution at various supersaturations. The dependencies of the growth rate and the nucleation rate on the supersaturation indicate the change of the growth mechanism from spiral growth to 2D nucleation. The difference in the growth rate for various faces is in agreement with the crystal morphologies derived from the attachment energy method and observed experimentally. The main result of the simulation is the evaluation of engineering limits for choosing appropriate external process conditions.     

Microtopographical studies of prism faces of potassium dihydrogen phosphate crystals

Surface structures on prism faces of potassium dihydrogen phosphate crystals grown from aqueous solutions and also by gel method are described and illustrated. Density of growth centres increases as the supersaturation of the mother liquor is increased. Gel grown crystals predominantly show rectangular growth hillocks on their prism faces. In the needle shaped crystals further nucleation extends predominantly along theC axis than at right angles to it. Influence of misoriented guest microcrystals on the growth of the prism faces is described.     

A microscopic time scale approximation to the behavior of the local slope on the faceted surface under a nonuniformity in supersaturation

The morphological stability of a growing faceted crystal is discussed. We argue that the interplay between nonuniformity in supersaturation on a growing facet and anisotropy of surface kinetics derived from the lateral motion of steps leads to a faceted instability. Qualitatively speaking, as long as the nonuniformity in supersaturation on the facet is not too large, it can be compensated for by a variation of step density along the facet, and the faceted crystal can grow in a stable manner. The problem can be modeled as a Hamilton-Jacobi equation for height of the crystal surface. The notion of a maximal stable region of a growing facet is introduced for microscopic time scale approximation of the original Hamilton-Jacobi equation. It is shown that the maximal stable region keeps its shape, determined by profile of the surface supersaturation, with constant growth rate by studying large time behavior of solution of macroscopic time scale approximation. A quantitative criterion for the facet stability is given.     

Correlation between growth of high-index faces, relative growth rates and crystallographic structure of crystal

According to contemporary crystal growth theories, crystals are bound by low-index faces which are the most slowly growing. However, high-index faces are observed in crystal habits more and more often. In this paper the growth of high-index faces is analysed from a crystallographic perspective. It is shown that the crystallographic structure of a given crystal, expressed by the trigonometric function of appropriate interfacial angles, influences to great degree the crystallisation process and the morphology of crystals, in particular the behaviour of high-index faces. Additionally, it is concluded that at particular crystallographic structure of a crystal, a given high-index face may exist in the habit and develop its size, although it grows much faster than the neighbouring faces. Received 31 July 2001     

Preparation and growth mechanism of micro spherical ammonium dinitramide crystal based on ultrasound-assisted solvent-antisolvent method

Micro-sized spherical ammonium dinitramide (ADN) crystals are successfully prepared by a facile ultrasound-assisted solvent-antisolvent recrystallization method without introducing any additives. The influences of the volume ratio of solvent to antisolvent, the antisolvent temperature and the ultrasound power on the micro-morphologies and properties of ADN crystals are studied systematically. The changes of morphology, particle size, crystal structure and melting point of the ADN crystals are characterized through scanning electron microscopy (SEM), laser particle size analyzer (LPSA), X-ray diffraction (XRD) and differential scanning calorimetry (DSC), respectively. The results show that the optimal experimental parameters for the ADN crystal of spherical morphology are as follows: the volume ratio of solvent to antisolvent is 1:50, the antisolvent temperature is 20 ℃, and the ultrasound power is 70 W. The predicted hexagonal-flake and spherical morphologies for the ADN are close to the experimental morphologies. The growth mechanism of the spherical ADN crystal changes with supersaturation of the ADN solution. As the degree of supersaturation increases, the growth models of the spherical ADN change from the spiral growth to the rough growth, and the morphologies of ADN change from the large-sized ADN ball to the small-sized ADN ball.     

Mutual solution of components during contact melting

Cadmium and zinc have been used to show that solid solutions occur in contact melting, the second component being deposited and undergoing segregation at dislocations and other defects. It is concluded that supersaturation zones are formed, whose configuration is due to the defects; any increase in these causes increased segregation of the second component in the contact zone. The rate of contact melting is higher in more imperfect crystals. Recovery in imperfect crystals exposed to ionizing radiation minimizes segregation of the second component; and the rate of contact melting becomes lower than that for unirradiated crystals.     

Surface morphology and growth kinetics of zinc single crystals as influenced by vapour diffusion

The effect of diffusion in the vapour phase on both the surface morphology and growth kinetics of zinc single crystals growing in the presence of argon has been investigated. The shift of the basal face in the normal direction and the growth of the edge of that face as a function of time have been determined at constant temperature and supersaturation and at argon pressures within the range 5–250 Torr as well as in high vacuum of 1 × 10⁻⁶ Torr. It has been found that the crystal size R and the edge length a change with time t following a linear law in the kinetic and a parabolic law in the diffusion regime respectively. The results obtained by kinetic investigations and morphological observations of the basal face are compared.     

Determination of solid material elastic modulus and surface energy based on JKR contact model

The JKR contact theory is employed to study the adhesion phenomena between two solid materials in intimate contact. The elastic contact modulus and the work of adhesion of solid materials are obtained during adhesion tests by utilizing a micro force-deflection measuring apparatus. Six of the plastic materials, including polyethylene polyoxymethlene (POM), polyamide (PA), terephthalate (PET), polyvinyl chloride (PVC), polypropylene (PP), and ultra-high molecular weight polyethylene (UHMWPE) are used to evaluate the adhesion effect implied by the JKR theory. Comparison is made between surface energy obtained from the adhesion tests with that by a dynamic contact angle analyser.Results show that the load/deflection data in the loading phase are in good agreement with the predictions of JKR equation, and the experimental data of unloading phase deviate significantly from the JKR theory. The phenomena of adhesion hysteresis in loading tests are responsible for these results due to the effects of molecular reconstruction on solid surfaces in contact. The work of adhesions, and hence surface energies of plastic materials, calculated by the best fitting of JKR equation with the experimental data in the loading phase, agree satisfactorily in a comparable manner with that obtained using the contact angle analyser.     

Modelling of Binder-Induced Agglomeration

From the analysis of pendular liquid bridge forces between spherical particles, a model has been developed to predict bridge rupture energies. Whilst this model has been shown to predict the correct trends in certain stages of agglomeration, it is limited by the assumptions of zero contact angle, toroidal bridge geometry, spherical particles and quasi-static rupture. The work described here is aimed at extending the model to more generally applicable conditions using direct measurement of bridge rupture energies between particles down to 3 μm in diameter under different physiochemical conditions. Initial results show that the spreading coefficient of the binder to the particle has a marked effect on the dynamic behaviour of the bridge itself and its subsequent geometry at equilibrium, i.e. for non-zero contact angles theoretical equations tend to over-predict the force of adhesion, whilst for zero contact angles the force of adhesion agrees with that predicted using the Laplace equations for constant curvature. On the other hand, the corrected expression for maximum separation distance shows good agreement with experimental results.     

Rolling resistance moment of microspheres on surfaces

In the current work, for the first time, the existence of a rolling moment of resistance of an adhesion bond between a microsphere and flat surface subjected to external dynamic force has been experimentally demonstrated. The rotational motion of spherical particles deposited on a wafer is excited in the 0–3.5?MHz range using a piezoelectric transducer. The approach is based on (i) the observation that the contribution of the rotational (rocking) motion to the axial displacement of the particle are few orders of magnitude higher than those of the purely axial motion and (ii) the existence of a relationship between the rotational natural frequency of the adhesion bond and the work of adhesion. The natural frequency of the rotational (rocking) motion is extracted from the low frequency components of the transient response of the particle in the axial direction, which is measured by a laser interferometer. The existing theoretical adhesion models for rolling resistance moment are evaluated using the experimental results. Good agreement between the theoretical predictions and experimental values is found.     

Crystallization of potash alum: effect of power ultrasound.

The influence of power ultrasound on the crystallization of potash alum was investigated. Experiments have been carried out in a batch stirred vessel. It was found that ultrasonic waves decrease the supersaturation limits and modify the morphology of the crystals produced. The average crystal size decreases with an increase of ultrasonic power. To investigate also the action of ultrasound on already existing crystals, crystals produced in silent conditions were suspended in saturated potash alum solution at various ultrasonic powers. The results show that ultrasound has also an abrasive effect on potash alum crystals for high power inputs.