ATR-FTIR spectroscopy and spectroscopic imaging of solvent and permeant diffusion across model membranes

The uptake and diffusion of solvents across polymer membranes is important in controlled drug delivery, effects on drug uptake into, for example, infusion bags and containers, as well as transport across protective clothing. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy has been used to monitor the effects of different solvents on the diffusion of a model compound, 4-cyanophenol (CNP) across silicone membrane and on the equilibrium concentration of CNP obtained in the membrane following diffusion. ATR-FTIR spectroscopic imaging of membrane diffusion was used to gain an understanding of when the boundary conditions applied to Fick's second law, used to model the diffusion of permeants across the silicone membrane do not hold. The imaging experiments indicated that when the solvent was not taken up appreciably into the membrane, the presence of discrete solvent pools between the ATR crystal and the silicone membrane can affect the diffusion profile of the permeant. This effect is more significant if the permeant has a high solubility in the solvent. In contrast, solvents that are taken up into the membrane to a greater extent, or those where the solubility of the permeant in the vehicle is relatively low, were found to show a good fit to the diffusion model. As such these systems allow the ATR-FTIR spectroscopic approach to give mechanistic insight into how the particular solvents enhance permeation. The solubility of CNP in the solvent and the uptake of the solvent into the membrane were found to be important influences on the equilibrium concentration of the permeant obtained in the membrane following diffusion. In general, solvents which were taken up to a significant extent into the membrane and which caused the membrane to swell increased the diffusion coefficient of the permeant in the membrane though other factors such as solvent viscosity may also be important.

In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads

In recent years, the use of swelling polymeric matrices for the encapsulation and controlled release of protein drugs has received significant attention. The purpose of the present study was to investigate the release of albumin, a model protein from alginate/hydroxypropyl-methylcellulose (HPMC) gel beads. A hydrogel system comprised of two natural, hydrophilic polymers; sodium alginate and HPMC was studied as a carrier of bovine serum albumin (BSA) which was used as a model protein. The morphology, bead size and the swelling ratio were studied in different physical states; fully swollen, dried and reswollen using scanning electron microscopy and image analysis. Finally the effect of different alginate/HPMC ratios on the BSA release profile in physiological saline solution was investigated. Swelling experiments revealed that the bead diameter increases with the viscosity of the alginate solution while the addition of HPMC resulted in a significant increase of the swelling ratio. The BSA release patterns showed that the addition of HPMC increased the protein-release rate while the release mechanism fitted the Peppas model. Alginate/HPMC beads prepared using the ionic gelation exhibited high BSA loading efficiency for all formulations. The presence of HPMC increased the swelling ability of the alginate beads while the particle size remained unaffected. Incorporation of HPMC in the alginate gels also resulted in improved BSA release in physiological saline solution. All formulations presented a non-Fickian release mechanism described by the Peppas model. In addition, the implementation of non-parametric tests showed significant differences in the release patterns between the alginate/HPMC and the pure alginate beads, respectively.

Investigation of wall-slip effect on paste release characteristic in flip-chip stencil printing process

As the trend toward further miniaturisation of pocket and handheld consumer electronic products continues apace, the requirements for even smaller solder joints will continue. With further reductions in the size of solder joints, the reliability of solder joints will become more and more critical to the long-term performance of electronic products. Solder joints play an important role in electronics packaging, serving both as electrical interconnections between the components and the board, and as mechanical support for components. With world-wide legislation for the removal/reduction of lead and other hazardous materials from electrical and electronic products, the electronics manufacturing industry has been faced with an urgent search for new lead-free solder alloy systems and other solder alternatives. In order to achieve high volume, low cost production, the stencil printing process and subsequent wafer bumping of solder paste has become indispensable. There is wide agreement in industry that the paste printing process accounts for the majority of assembly defects, and most defects originate from poor understanding of the effect of printing process parameters on printing performance. The printing of ICAs and lead-free solder pastes through the very small stencil apertures required for flip chip applications was expected to result in increased stencil clogging and incomplete transfer of paste to the printed circuit pads. Paste release from the stencil apertures is dependent on the interaction between the solder paste, surface pad and aperture wall; including its shape. At these very narrow aperture sizes the paste rheology becomes crucial for consistent paste withdrawal because for smaller paste volumes surface tension effects become dominant over viscous flow. Successful aperture filling and release will greatly depend on the rheology of the paste material. Wall-slip plays an important role in characterising the flow behaviour of solder paste materials. The wall- slip arises due to the various attractive and repulsive forces acting between the solder particles and the walls of the measuring geometry. These interactions could lead to the presence of a thin solvent layer adjacent to the wall, which gives rise to slippage. The wall slip effect can play an important role in ensuring successful paste release after the printing process. The aim of this study was to investigate the influence of the paste microstructure on slip formation for the paste materials (lead-free solder paste and isotropic conductive adhesives). The effect of surface roughness on the paste viscosity was investigated. It was also found that altering the surface roughness of the parallel plate measuring geometry did not significantly eliminate wall slip as was expected. But results indicate that the use of a relatively rough surface helps to increase paste adhesion to the plates, inducing structural breakdown of the paste. Most importantly, the study also demonstrated on how the wall slip formation in the paste material could be utilised for understanding of the paste microstructure and its flow behaviour

Solder paste characterisation: towards the development of quality control (QC) tool

Purpose – The purpose of this paper is to develop a quality control tool based on rheological test methods for solder paste and flux media. Design/methodology/approach – The rheological characterisation of solder pastes and flux media was carried out through the creep-recovery, thixotropy and viscosity test methods. A rheometer with a parallel plate measuring geometry of 40mm diameter and a gap height of 1mm was used to characterise the paste and associated flux media. Findings – The results from the study showed that the creep-recovery test can be used to study the deformation and recovery of the pastes, which can be used to understand the slump behaviour in solder pastes. In addition, the results from the thixotropic and viscosity test were unsuccessful in determining the differences in the rheological flow behaviour in the solder pastes and the flux medium samples. Research limitations/implications – More extensive rheological and printing testing is needed in order to correlate the findings from this study with the printing performance of the pastes. Practical implications – The rheological test method presented in the paper will provide important information for research and development, quality control and production staff to facilitate the manufacture of solder pastes and flux media. Originality/value – The paper explains how the rheological test can be used as a quality control tool to identify the suitability of a developmental solder paste and flux media used for the printing process.

An investigation into the rheological properties of different lead-free solder pastes for surface mount applications

Purpose – The purpose of this paper is to investigate the rheological behaviour of three different lead-free solder pastes used for surface mount applications in the electronic industry.Design/methodology/approach – This study concerns the rheological measurements of solder paste samples and is made up of three parts. The first part deals with the measurement of rhelogical properties with three different measuring geometries, the second part looks into the effect of frequencies on oscillatory stress sweep measurements and the final part reports on the characterisation and comparison of three different types of Pb-free solder pastes. Findings – Among the three geometries, the serrated parallel plate was found effective in minimising the wall-slip effect. From the oscillatory stresssweep data with different frequencies; it was observed that the linear visco-elastic region is independent of frequency for all the solder paste samples. To understand the shear thinning behaviour of solder paste, the well known Cross and Carreau models were fitted to the viscosity data. Moreover,creep-recovery and dynamic frequency-sweep tests were also carried out without destroying the sample’s structure and have yielded useful information on the pastes behaviour.Research limitations/implications – More extensive research is needed to fully characterise the wall-slip behaviour during the rheological measurements of solder pastes. Practical implications – The rheological test results presented in this paper will be of important value for research and development, quality control and facilitation of the manufacturing of solder pastes and flux mediums. Originality/value – This paper shows how wall-slip effects can be effectively avoided during rheological measurements of solder pastes. The paper also outlines how different rheological test methods can be used to characterise solder paste behaviours

Modelling of the time-dependent flow behaviour of lead-free solder pastes used for flip-chip assembly applications

The market for solder paste materials in the electronic manufacturing and assembly sector is very large and consists of material and equipment suppliers and end users. These materials are used to bond electronic components (such as flip-chip, CSP and BGA) to printed circuit boards (PCB's) across a range of dimensions where the solder interconnects can be in the order of 0.05mm to 5mm in size. The non-Newtonian flow properties exhibited by solder pastes during its manufacture and printing/deposition phases have been of practical concern to surface mount engineers and researchers for many years. The printing of paste materials through very small-sized stencil apertures is known to lead to increased stencil clogging and incomplete transfer of paste to the substrate pads. At these very narrow aperture sizes the paste rheology and particle-wall interactions become crucial for consistent paste withdrawal. These non-Newtonian effects must be understood so that the new paste formulations can be optimised for consistent printing. The focus of the study reported in this paper is the characterisation of the rheological properties of solder pastes and flux mediums, and the evaluation of the effect of these properties on the pastes' printing performance at the flip-chip assembly application level. Solder pastes are known to exhibit a thixotropic behaviour, which is recognised by the decrease in apparent viscosity of paste material with time when subjected to a constant shear rate. The proper characterisation of this time-dependent theological behaviour of solder pastes is crucial for establishing the relationships between the pastes' structure and flow behaviour; and for correlating the physical parameters with paste printing performance. In this paper, we present a number of methods which have been developed for characterising the time-dependent and non-Newtonian rheological behaviour of solder pastes and flux mediums as a function of shear rates. We also present results of the study of the rheology of the solder pastes and flux mediums using the structural kinetic modelling approach, which postulates that the network structure of solder pastes breaks down irreversibly under shear, leading to time and shear dependent changes in the flow properties. Our results show that for the solder pastes used in the study, the rate and extent of thixotropy was generally found to increase with increasing shear rate. The technique demonstrated in this study has wide utility for R&D personnel involved in new paste formulation, for implementing quality control procedures used in solder paste manufacture and packaging; and for qualifying new flip-chip assembly lines

Influence of solder paste components on rheological behaviour

Rheological properties of solder pastes are very important for a high quality surface mount technology process. The stencil/screen printing process of solder pastes is one of the most critical steps in the SMT assembly process, as most of the assembly defects can often be shown to originate from paste rheology and associated poor printing performance. This paper concerns an investigation of the effect of solder paste composition on the rheological properties and behaviour of four different solder pastes. We report on the evaluation of three different paste formulations based on the no-clean flux composition, with different alloy composition, metal content and particle size using a range of rheological characterisation techniques - including viscosity measurements, yield stress, oscillatory and creep-recovery tests. Our results show that in the viscosity test, all solder pastes exhibited a shear thinning behaviour in nature with different highest maximum viscosity. In the region of shear thinning behaviour the paste 3 delivered the best results. Viscosity test helps to understand the solid and cohesive behaviour of solder pastes. Good solid and cohesive behaviour indicates a good paste roll and helps to avoid paste bleeding. The yield stress test has been used to study the effect of temperature on the flow behaviour of solder pastes. Yield stress was measured for a range of temperature from 15deg C to 35deg C with an increment of 5degC. The result indicated a decreasing of the yield stress point if the temperature was increased. Paste 4 has shown the minimum dependence on temperature. The oscillatory test has been used to find out the linear visco-elastic range and to study the solid and liquid like behaviours of solder pastes. Paste 1 indicated the biggest linear visco-elastic region (LVR) and the highest value of G' and G" which means solder paste 1 will be needed a higher squeegee pressure in the printing process. In the creep recovery test paste 4 showed the best- - recovery and the lowest values of creep and recovery compliance which indicated a good printing behaviour. The test also has showed the solder paste with smaller particle size exhibit less recovery

Preparation of o/w emulsions stabilized by solid particles and their characterization by oscillatory rheology

The purpose of this investigation was to examine the preparation and characterisation of hexane-in-water emulsions stabilised by clay particles. These emulsions, called Pickering emulsions, are characterised by the adsorption of solid particles at the oil/water (o/w) interface. The development of an elastic film at the o/w interface following the adsorption of colloidal particles helps to promote emulsion stability. Three different solid materials were used: silica sand, kaolin, and bentonite. Particles were added to the liquid mixtures in the range of 0.5–10 g dm−3. Emulsions were prepared using o/w ratios of 0.1, 0.2, 0.3, and 0.4. The effect of sodium chloride, on the stability of the prepared emulsions, was assessed in the range of 0–0.5 mol dm−3. In addition the use of a cationic surfactant hexadecyl-trimethylammonium bromide (CTAB) as an aid to improving emulsion stability was assessed in the concentration range of 0–0.05% (w/v). Characterisation of emulsion stability was realised through measurements of rheological properties including non-Newtonian viscosity, the elastic modulus, G', the loss modulus, G", and complex modulus, G*. The stability of the emulsions was evaluated immediately after preparation and 4 weeks later. Using the stability criteria, that for highly stable emulsions: G' > G" and both G' and G" are independent of frequency (varpi) it was concluded that highly stable emulsions could be prepared using a bentonite concentration of 2% (or more); an o/w ratio greater than 0.2; a CTAB concentration of 0.01%; and a salt concentration of 0.05 M or less—though salt was required.

Microcirculatory hemodynamics and endothelial dysfunction in systemic lupus erythematosus.

OBJECTIVE: Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE. The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. METHODS AND RESULTS: DSS was calculated using (mean diastolic velocity x 8 x blood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, -2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; P

Fate of inflammatory neutrophils within the joint

OBJECTIVE: Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE. The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. METHODS AND RESULTS: DSS was calculated using (mean diastolic velocity x 8 x blood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, -2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; P

Formulation and characterisation of tetracycline-containing bioadhesive polymer networks designed for the treatment of periodontal disease.

This study described the drug release, rheological (dynamic and flow) and textural/mechanical properties of a series of formulations composed of 15% w/w polymethylvinylether-co-maleic anhydride (PMVE-MA), 0-9% w/w polyvinylpyrrolidone (PVP) and containing 1-5% w/w tetracycline hydrochloride, designed for the treatment of periodontal disease. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of PVP sequentially increased the zero-rate viscosity (derived from the Cross model) and the hardness and compressibility of the formulations (derived from texture profile analysis). These affects may be accredited to increased polymer entanglement and, in light of the observed synergy between the two polymers with respect to their textural and rheological properties, interaction between PVP and PMVE-MA. Increasing the concentration of PVP increased the storage and loss moduli yet decreased the loss tangent of all formulations, indicative of increased elastic behaviour. Synergy between the two polymers with respect to their viscoelastic properties was observed. Increased adhesiveness, associated with increased concentrations of PVP was ascribed to the increasing bioadhesion and tack of the formulations. The effect of increasing drug concentration on the rheological and textural properties was dependent on PVP concentration. At lower concentrations (0, 3% w/w) no effect was observed whereas, in the presence of 9% w/w PVP, increasing drug concentration increased formulation elasticity, zero rate viscosity, hardness and compressibility. These observations were ascribed to the greater mass of suspended drug in formulations containing the highest concentration of PVP. Drug release from formulations containing 6 and 9% PVP (and 5% w/w drug) was prolonged and swelling/diffusion controlled. Based on the drug release, rheological and textural properties, it is suggested that the formulation containing 15% w/w PMVE-MA, 6% w/w PVP and tetracycline hydrochloride (5% w/w) may be useful for the treatment of periodontal disease.

Predicting physical properties of ionic liquids

A simple method to predict the densities of a range of ionic liquids from their surface tensions, and vice versa, using a surface-tension-weighted molar volume, the parachor, is reported. The parachors of ionic liquids containing 1-alkyl-3-methylimidazolium cations were determined experimentally, but were also calculated directly from their structural compositions using existing parachor contribution data for neutral compounds. The calculated and experimentally determined parachors were remarkably similar, and the latter data were subsequently employed to predict the densities and surface tensions of the investigated ionic liquids. Using a similar approach, the molar refractions of ionic liquids were determined experimentally, as well as calculated using existing molar refraction contribution data for uncharged compounds. The calculated molar refraction data were employed to predict the refractive indices of the ionic liquids from their surface tensions. The errors involved in the refractive index predictions were much higher than the analogous predictions employing the parachor, but nevertheless demonstrated the potential for developing parachor and molar refraction contribution data for ions as tools to predict ionic liquid physical properties.

Co-melt fluidised bed granulation of pharmaceutical powders: Improvements in drug bioavailability

This study investigates the use of co-melt fluidised bed granulation for the agglomeration of model pharmaceutical powders, namely, lactose mono-hydrate, PEG 10000, poly-vinyl pyrolidone and ibuprofen as a model drug. Granulation within the co-melt system was found to follow a nucleationâ??steady growthâ??coating regime profile. Using high molecular weight PEG binder, the granulation mechanism and thus the extent of granulation was found to be significantly influenced by binder viscosity. The compression properties of the granulate within the hot fluidised bed were correlated using a novel high temperature experimental procedure. It was found that the fracture stress and fractural modulus of the materials under hot processing conditions were orders of magnitude lower than those measured under ambient conditions. A range of particle velocities within the granulator were considered based on theoretical models. After an initial period of nucleation, the Stokes deformation number analysis indicated that only velocities within the high shear region of the fluidised bed were sufficient to promote significant granule deformation and therefore, coalescence. The data also indicated that larger granules de-fluidised preventing agglomeration by coalescence. Furthermore, experimental data indicated that dissipation of the viscous molten binder to the surface was the most important factor in the latter stages of the granulation process. From a pharmaceutical perspective the inclusion of the model drug, ibuprofen, combined with PVP in the co-melt process proved to be highly significant. It was found that using DSC analysis on the formulations that the decrease in the heat of fusion associated with the melting of ibuprofen within the FHMG systems may be attributed to interaction between PVP and ibuprofen through inter-molecular hydrogen bonding. This interaction decreases the crystallinity of ibuprofen and facilitates solubilisation and bioavailability within the solid matrix.

Polymer conditioning of alum sludge and discrepancies between estimates of the optimum dosage

The paper outlines the effects of polymer conditioning on alum sludge properties, such as floc size, density, fractal dimension (DF) and rheological properties. Experimental results demonstrate that polymer conditioning of alum sludge leads to: larger floc size with a plateau reached in higher doses; higher densities associated with higher doses; increased degree of compactness; and an initial decrease followed by an increase of supernatant viscosity with continued increase in polymer dose. The secondary focus of this paper dwells on a comparison of the estimates of optimum dose using different criteria that emanate from established dewatering tests such as CST, SRF, liquid phase viscosity and modified SRF as well as a simple settlement test in terms of CML30. Alum sludge was derived from a water works treating coloured, low-turbidity raw waters.

Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease

This study describes the formulation, characterisation and preliminary clinical evaluation of mucoadhesive, semi-solid formulations containing hydroxyethylcellulose (HEC, 1-5%, w/w), polyvinylpyrrolidine (PVP, 2 or 3%, w/w), poly carbophil (PC, 1 or 3%, w/w) and tetracycline (5%, w/w, as the hydrochloride). Each formulation was characterised in terms of drug release, hardness, compressibility, adhesiveness (using a texture analyser in texture profile analysis mode), syringeability (using a texture analyser in compression mode) and adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode). The release exponent for the formulations ranged from 0.78+/-0.02 to 1.27+/-0.07, indicating that drug release was non-diffusion controlled. Increasing the concentrations of each polymeric component significantly increased the time required for 10 and 30% release of the original mass of tetracycline, due to both increased viscosity and, additionally, the unique swelling properties of the formulations. Increasing concentrations of each polymeric component also increased the hardness, compressibility, adhesiveness, syringeability and mucoadhesion of the formulations. The effects on product hardness, compressibility and syringeability may be due to increased product viscosity and, hence, increased resistance to compression. Similarly, the effects of these polymers on adhesiveness/mucoadhesion highlight their mucoadhesive nature and, importantly, the effects of polymer state (particularly PC) on these properties. Thus, in formulations where the neutralisation of PC was maximally suppressed, adhesiveness and mucoadhesion were also maximal. Interestingly, statistical interactions were primarily observed between the effects of HEC and PC on drug release, mechanical and mucoadhesive properties. These were explained by the effects of HEC on the physical state of PC, namely swollen or unswollen. In the preliminary clinical evaluation, a formulation was selected that offered an appropriate balance of the above physical properties and contained 3% HEC, 3% PVP and 1% PC, in addition to tetracycline 5% (as the hydrochloride). The clinical efficacy of this (test) formulation was compared to an identical tetracycline-devoid (control) formulation in nine periodontal pockets (greater than or equal to 5 mm depth). One week following administration of the test formulation, there was a significant improvement in periodontal health as identified by reduced numbers of sub-gingival microbial pathogens. Therefore, it can be concluded that, when used in combination with mechanical plaque removal, the tetracycline-containing semi-solid systems described in this study would augment such therapy by enhancing the removal of pathogens, thus improving periodontal health. (C) 2000 Elsevier Science B.V. All rights reserved.