116 results found
Shah UV, Karde V, Ghoroi C, et al., 2017, Influence of particle properties on powder bulk behaviour and processability, International Journal of Pharmaceutics, Vol: 518, Pages: 138-154, ISSN: 1873-3476
Understanding interparticle interactions in powder systems is crucial to pharmaceutical powder processing. Nevertheless, there remains a great challenge in identifying the key factors affecting interparticle interactions. Factors affecting interparticle interactions can be classified in three different broad categories: powder properties, environmental conditions, and powder processing methods and parameters. Although, each of these three categories listed is known to affect interparticle interactions, the challenge remains in developing a mechanistic understanding on how combination of these three categories affect interparticle interactions. This review focuses on the recent advances on understanding the effect of powder properties, particularly particle properties, its effect on interparticle interactions and ultimately on powder bulk behaviour. Furthermore, this review also highlights how particle properties are affected by the particle processing route and parameters. Recent advances in developing a particle processing route to prepare particles with desired properties allowing desired interparticle interaction to deliver favoured powder bulk behaviour are also discussed. Perspectives for the development of potential particle processing approaches to control interparticle interaction are presented.
Hadjittofis E, Zhang GGZ, Heng JYY, 2017, Influence of sample preparation on IGC measurements: the cases of silanised glass wool and packing structure, RSC Advances, Vol: 7, Pages: 12194-12200, ISSN: 2046-2069
Inverse Gas Chromatography (IGC) is an established technique for the determination of the surface energy heterogeneity of various types of materials, including particulate and fibrous materials. However, variability in sample and column preparation may lead to low reproducibility of data. In this work, the influence of two aspects of chromatographic column preparation; the amount of silanised glass wool and the packing structure of mixtures of particulate materials, on IGC measurements were investigated using a combined experimental and modelling approach. In silico experiments were used to examine these factors for a range of materials with different surface energy. We report here, that the packing structure of particulate materials in the column does not significantly affect the measurements and the results. However, the contribution of the silanised glass wool needs to be corrected, particularly for materials of low surface area or low surface energy. This work demonstrates the importance of column preparation and the need for standardisation of packing protocols for robust experimental determination of surface energy heterogeneity.
Heng JYY, 2017, Determining surface energetics of solid surfaces, NATO Science for Peace and Security Series A: Chemistry and Biology, Pages: 133-144
© Springer Science+Business Media B.V. 2017. The most fundamental description of an interface is the thermodynamic free energy per unit area, γij governs a range of solid-solid, solid-liquid and solidvapour interactions. The determination of the solid-vapour free energy is not straight-forward. In this chapter, conventional experimental techniques such as; sessile drop contact angle measurements, capillary rise and Wilhelmy plate is presented. Models for the determination of surface energy from contact angles are discussed. Furthermore, recent developments in inverse gas chromatography and dynamic vapour sorption approaches for the evaluation of the solid surface free energy are also described.
Parambil JV, Heng JYY, 2017, Seeding in crystallisation, Engineering Crystallography: From Molecule to Crystal to Functional Form, Editors: Roberts, Docherty, Tamura, Publisher: Springer Netherlands, Pages: 235-245, ISBN: 9789402411157
Crystal seeding is the process of adding homogeneous or heterogeneous crystals to a crystallising solution to nucleate and/or grow more crystals. Seeding has emerged as one of the most critical steps in optimising the crystallisation process (O’Sullivan B, Smith B, Baramidze G, Recent advances for seeding a crystallization process. Mettler Toledo Auto-Chem, Columbia, 2012). An aptly designed seeding technique would ensure product reproducibility between batches or over time. This is achieved primarily by controlling the crystal size distribution and polymorphism of the crystals that are formed. In this chapter, aspects of crystal nucleation, the importance of seeding and crystallisation methods employed will be discussed.
Hadjittofis E, Das SC, Zhang GGZ, et al., 2016, Interfacial Phenomena, Developing Solid Oral Dosage Forms Pharmaceutical Theory and Practice, Editors: Qiu, Chen, Zhang, Yu, Mantri, Publisher: Academic Press, ISBN: 9780128024478
This book covers the essential principles of physical pharmacy, biopharmaceutics, and industrial pharmacy, and their application to the research and development process of oral dosage forms.
Soh WM, Tan J, Heng JYY, et al., 2016, Production of cenospheres from coal fly ash through vertical thermal flame (VTF) process, 4th Asia Conference on Mechanical and Materials Engineering, Publisher: Trans Tech Publications, Pages: 7-10, ISSN: 0255-5476
Coal fly ash is a complex mixture of anthropogenic materials produced during the combustion of pulverised coal in coal fired power plants. They pose environmental concerns that lead to air and water pollution. Effort has been done to reduce the production of coal fly ash or to extract potentially valuable products from coal fly ash, such as cenospheres. Cenospheres are light, low density, thin-walled hollow ceramic microsphere with unique properties. Conventional cenosphere production methods involve the separation of cenospheres from coal fly ash. Due to its small quantities in fly ash (1 % wt.), separation process results in low production of cenospheres. In this work, an attempt by applying a vertical thermal flame (VTF) process is done to produce cenospheres from coal fly ash. Particle size of coal fly ash 63 to 90 μm and 90 to 126 μm are selected to undergo the VTF process. Effect of size of precursor, number of passes through the thermal process, density, morphology and particles size of generated spheres are evaluated. The results show that different sizes of coal fly ash and number of passes through the VTF process affect the morphology of obtained spheres and the overall real density. Further optimization of the VTF process design in terms of heat source and the feeding mechanism are required to increase the transformation of coal fly ash to cenospheres.
Lapidot T, Heng JYY, 2016, Functionalized mesoporous silica for the control of crystallization fouling, Industrial & Engineering Chemistry Research, Vol: 55, Pages: 11475-11479, ISSN: 1520-5045
A seeding study to test the effectiveness of nanoparticles in mitigating crystallization fouling is reported. The effect of functionalized mesoporous silica particles on calcium sulfate crystallization was studied through a series of batch crystallization experiments. Tested surface chemistries include nonfunctionalized silica (hydrophilic), methyl (hydrophobic) propyl amine (basic), propyl sulfonic acid (acidic), and triaminetetraacitic acid (TAAcOH, chelating). Crystallization was tracked online using electrical conductivity to determine concentration as a function of time, which was used to calculate induction time and growth rate. At a loading of 0.1 mg/gsol, amine functionalized particles were found to be the most effective at reducing induction time, while TAAcOH particles were found to significantly increase induction time. The efficacy of TAAcOH particles was further tested at various loadings and was found to increase induction time 6-fold at a loading of 0.5 mg/gsol. Despite having a profound effect on induction time, growth rates remained relatively constant for all surface chemistries and loadings. Here, we show that the seed surface chemistry can play a major role in the control of calcium sulfate crystallization.
Parambil JV, Poornachary SK, Tan RBH, et al., 2016, Influence of solvent polarity and supersaturation on template-induced nucleation of carbamazepine crystal polymorphs, Journal of Crystal Growth, Vol: 469, Pages: 84-90, ISSN: 1873-5002
Studies on the use of template surfaces to induce heterogeneous crystal nucleation have gained momentum in recent years-with potential applications in selective crystallisation of polymorphs and in the generation of seed crystals in a continuous crystallisation process. In developing a template-assisted solution crystallisation process, the kinetics of homogeneous versus heterogeneous crystal nucleation could be influenced by solute-solvent, solute-template, and solvent-template interactions. In this study, we report the effect of solvents of varying polarity on the nucleation of carbamazepine (CBZ) crystal polymorphs, a model active pharmaceutical ingredient. The experimental results demonstrate that functionalised template surfaces are effective in promoting crystallisation of either the metastable (form II) or stable (form III) polymorphs of CBZ only in moderately (methanol, ethanol, isopropanol) and low polar (toluene) solvents. A solvent with high polarity (acetonitrile) is thought to mask the template effect on heterogeneous nucleation due to strong solute-solvent and solvent-template interactions. The current study highlights that a quality-by-design (QbD) approach-considering the synergistic effects of solute concentration, solvent type, solution temperature, and template surface chemistry on crystal nucleation-is critical to the development of a template-induced crystallisation process.
Shah UV, Jahn NH, Huang S, et al., 2016, Crystallisation via novel 3D nanotemplates as a tool for protein purification and bio-separation, Journal of Crystal Growth, Vol: 469, Pages: 42-47, ISSN: 1873-5002
This study reports an experimental validation of the surface preferential nucleation of proteins on the basis of a relationship between nucleant pore diameter and protein hydrodynamic diameter. The validated correlation was employed for the selection of nucleant pore diameter to crystallise a target protein from binary, equivolume protein mixture. We report proof-of-concept preliminary experimental evidence for the rational approach for crystallisation of a target protein from a binary protein mixture on the surface of 3D nanotemplates with controlled surface porosity and narrow pore-size distribution selected on the basis of a relationship between the nucleant pore diameter and protein hydrodynamic diameter. The outcome of this study opens up an exciting opportunity for exploring protein crystallisation as a potential route for protein purification and bio-separation in both technical and pharmaceutical applications.
Smith RR, Shah UV, Parambil JV, et al., 2016, The effect of polymorphism on surface energetics of D-mannitol polymorphs, AAPS Journal, Vol: 19, Pages: 103-109, ISSN: 1550-7416
The aim of this work was to assess the effect of different crystalline polymorphism on surface energetics of D-mannitol using finite dilution inverse gas chromatography (FD-IGC). Pure α, β and δ polymorphs were prepared via solution crystallisation and characterised by powder X-ray diffraction (P-XRD). The dispersive surface energies were found to range from 43 to 34 mJ/m(2), 50 to 41 mJ/m(2), and 48 to 38 mJ/m(2) , for α, β, and δ, respectively, for surface coverage ranging from 0.006 to 0.095. A deconvolution modelling approach was employed to establish their energy sites. The primary sites corresponded to maxima in the dispersive surface energy of 37.1 and 33.5; 43.3 and 39.5; and 38.6, 38.4 and 33.0; for α, β, and δ, respectively. This methodology was also extended to an α-β polymorph mixture to estimate the amount of the constituent α and β components present in the sample. The dispersive surface energies of the α-β mixture were found to be in the range of 48 to 37 mJ/m(2) with 40.0, 42.4, 38.4 and 33.1 mJ/m(2) sites. The deconvolution modelling method extracted the energy contribution of each of the polymorphs from data for the polymorphic mixture. The mixture was found to have a β-polymorph surface content of ∼19%. This work shows the influence of polymorphism on surface energetics and demonstrates that FD-IGC coupled with a simple modelling approach to be a powerful tool for assessing the specific nature of this energetic distribution including the quantification of polymorphic content on the surface.
Biegaj K, Kwek JW, Lukas T, et al., 2016, Novel coupling of a capacitive probe with a dynamic vapor sorption (DVS) instrument for the electrostatic measurements of powders, Industrial & Engineering Chemistry Research, Vol: 55, Pages: 5585-5589, ISSN: 1520-5045
Powders may become electrostatically charged due to friction. This phenomenon may lead to unusual outcomes such as increased cohesion, adhesion, and poor flow. It is still a challenge to investigate the electrostatic properties of powders due to restrictions associated with existing methods. The objective is to present a novel coupling method with the dynamic vapor sorption (DVS) instrument using a capacitive probe to measure the electrostatic potential of powders. The critical factors affecting measurements are defined to aid experimental design. The method was tested with glass beads tribocharged after contact with stainless steel to assess the feasibility of the setup via analysis of the repeatability and reproducibility of the data generated. The results obtained show that electrostatic measurements can be performed with minimum noise interference, short equilibration time of 15 min, and high reproducibility based on 19 measurements. Stability of experimental conditions of ±0.1 °C and ±0.2% RH is achieved.
Yao Z, Wu D, Tang J, et al., 2016, A novel colored talc filler: preparation and surface property determination using two distinct methods, Chemometrics and Intelligent Laboratory Systems, Vol: 155, Pages: 54-61, ISSN: 1873-3239
Lapidot T, Sedransk Campbell KL, Heng JY, 2016, Model for interpreting surface crystallization using quartz crystal microbalance: theory and experiments, Analytical Chemistry, Vol: 88, Pages: 4886-4893, ISSN: 1086-4377
Surface crystallization of calcium sulfate was investigated using a dissipation crystal quartz microbalance (QCM-D) together with microscopy to understand the mechanical property changes occurring during the growth process. The use of optical microscopy and SEM revealed that needle-shaped crystals grow as clusters on the QCM sensor’s surface, not in uniform layers. As crystallization growth progressed, QCM-D revealed inversions between negative and positive frequency shifts. This behavior, a function of the growth of crystals in clusters, is not adequately predicted by existing models. As such, a new mass-to-frequency conversion model is proposed herein to explain the observed frequency inversions. This model is derived from a lumped element approach with point-contact loading and Mason equivalent circuit theory. Critically, the physical phenomena occurring form the basis of the model, particularly addressing the three sources of impedance. When a crystal nucleates and grows, its inertial impedance is considered along with a Kelvin–Voigt link with a hydration layer. A comparison between the proposed model and experimental data, of both frequency and dissipation data for the first four harmonics, shows good agreement for the supersaturations (S = C/C*) of S = 3.75, S = 3.48, and S = 3.22. Additionally, significant improvements over existing models for the case of surface crystallization are observed. The proposed model was therefore able to explain that frequency inversions are caused by a shift from inertia-dominated to elastic-dominated impedance, occurring as a result of crystal growth. Using the nucleation induction time and nucleation rates, determined with imaging, an additional understanding of the crystals’ mechanical properties (stiffness and dampening) was obtained.
Yao Z, Heng JYY, Lanceros-Méndez S, et al., 2016, Study on the surface properties of colored talc filler (CTF) and mechanical performance of CTF/acrylonitrile-butadiene-styrene composite, Journal of Alloys and Compounds, Vol: 676, Pages: 513-520, ISSN: 1873-4669
Hadjittofis E, Zhang GGZ, Heng J, 2016, Growing macroscopic hydrates using a bioinspired approach and investigating dehydration induced polymorphism, Pages: 960-962
Growing of macroscopic single crystals of organic materials is not necessarily a straight forward procedure. Carbamazepine dihydrate is one of these cases. Traditional approaches of crystallization of this, particular, compound using mixtures of alcohols with water lead to crystals with high aspect ratios (needle shaped or high aspect ratio plates)1. These crystals are not suitable for wettability or XPS measurements on individual facets2. In this work, a bioinspired crystallization method is employed for the growth of macroscopic carbamazepine dihydrate crystals.
Wang Z, Shah UV, Olusanmi D, et al., 2015, Measuring the sticking of mefenamic acid powders on stainless steel surface, International Journal of Pharmaceutics, Vol: 496, Pages: 407-413, ISSN: 0378-5173
Al Nasser WN, Shah UV, Nikiforou K, et al., 2015, Effect of silica nanoparticles to prevent calcium carbonate scaling using an in situ turbidimetre, Chemical Engineering Research and Design, Vol: 110, Pages: 98-107, ISSN: 0263-8762
Scale minerals in the oil and gas industries are a major concern to reservoir and operations engineering. The main types of oilfield scales found are carbonate and sulfate scales. Calcium carbonate (CaCO3) is a major component of fouling in heat transfer surfaces across different sectors of industry, resulting in additional capital, maintenance and operating costs. Various techniques, including the use of chemical inhibitors, have been used to prevent the formation of scale. In the last decade, there have been considerable advances in the development of chemicals, effective in small concentrations for the control of scale deposits.The purpose of this study was to investigate the possibilities of utilizing nanoparticles as sacrificial surface for enhancement and control of the nucleation and crystallization of CaCO3, as a method for fouling mitigation. Here, the turbidity profile of the solution, using a light reflection technique, is used to monitor the process. The outcomes of this study will improve revenues by preventing the unscheduled shutdown of facilities and avoidance of using an excess of scale inhibitors. Silica nanoparticles of different size and surface functional groups were added to the solution. The results showed a reduction in the induction period, consequently indicating improved control over crystallization. Modified silica nanotemplates exhibited the highest reduction in induction time at room temperature. This resulted in preventing scale formation on the wall of the crystallizer. This conclusion is very significant, and further studies are proposed, which will attempt to understand the mechanisms of reactions between the nanoparticles and scaling ions.
Hedberg SHM, Heng JYY, Williams DR, et al., 2015, Micro scale self-interaction chromatography of proteins: a mAb case-study, Journal of Chromatography A, Vol: 1434, Pages: 57-63, ISSN: 0412-3425
Self-interaction chromatography is known to be a fast, automated and promising experimental technique for determination of B22, but with the primary disadvantage of needing a significant amount of protein (>50 mg). This requirement compromises its usage as a technique for the early screening of new biotherapeutic candidates. A new scaled down SIC method has been evaluated here using a number of micro LC columns of different diameters and lengths, using typically 10 times less stationary phase than traditional SIC. Scale-down was successfully accomplished using these micro-columns, where the SIC results for a range of differing columns sizes were in agreement, as reflected by k′, B22 and column volumes data. The results reported here demonstrate that a scaled down version of SIC can be easily implemented using conventional liquid chromatography system where the final amount of mAbs used was 10 times less than required by conventional SIC methodologies.
Shah UV, Wang Z, Olusanmi D, et al., 2015, Effect of milling temperatures on surface area, surface energy and cohesion of pharmaceutical powders, International Journal of Pharmaceutics, Vol: 495, Pages: 234-240, ISSN: 0378-5173
Cai X, Yang H, Heng JYY, 2015, Preface, POWDER TECHNOLOGY, Vol: 282, Pages: 1-1, ISSN: 0032-5910
Hedberg SHM, Heng JYY, Williams DR, et al., 2015, Self-interaction chromatography of mAbs: accurate measurement of dead volumes, Pharmaceutical Research, Vol: 32, Pages: 3975-3985, ISSN: 1573-904X
Purpose: Measurement of the second virial coefficient B22 for proteins using self-interaction chromatography (SIC) is becoming an increasingly important technique for studying their solution behaviour. In common with all physicochemical chromatographic methods, measuring the dead volume of the SIC packed column is crucial for accurate retention data; this paper examines best practise for dead volume determination.Method: SIC type experiments using catalase, BSA, lysozyme and a mAb as model systems are reported, as well as a number of dead column measurements. Results: It was observed that lysozyme and mAb interacted specifically with Toyopearl AF-Formyl dead columns depending upon pH and [NaCl], invalidating their dead volume usage. Toyopearl AF-Amino packed dead columns showed no such problems and acted as suitable dead columns without any solution condition dependency. Dead volume determinations using dextran MW standards with protein immobilised SIC columns provided dead volume estimates close to those obtained using Toyopearl AF-Amino dead columns. Conclusion: It is concluded that specific interactions between proteins, including mAbs, and select SIC support phases can compromise the use of some standard approaches for estimating the dead volume of SIC columns. Two other methods were shown to provide good estimates for the dead volume.
Shah UV, Amberg C, Diao Y, et al., 2015, Heterogeneous nucleants for crystallogenesis and bioseparation, CURRENT OPINION IN CHEMICAL ENGINEERING, Vol: 8, Pages: 69-75, ISSN: 2211-3398
Lee K-Y, Blaker J, Murakami R, et al., 2015, Phase behavior of water-in-oil emulsions stabilised solely by hydrophobised bacterial cellulose nanofibrils, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
Shah UV, Parambil JV, Williams DRM, et al., 2015, Preparation and characterisation of 3D nanotemplates for protein crystallisation, Powder Technology, Vol: 282, Pages: 10-18, ISSN: 0032-5910
Heterogeneous template nucleants are gaining pace as a favoured tool for crystallisation of proteins that may be otherwise difficult to crystallise. A systematic understanding on protein-nucleant interactions has to be developed to enable the development of nucleants for a wide spectrum of biological macromolecules. Thorough characterisation of the nucleants is the key starting point to achieve this aim. This report focuses on the method to produce and characterise functionalised 3D nanotemplates with controlled porosity in the range of 3-22. nm and surface chemistry that can vary from highly hydrophilic to highly hydrophobic in nature. BET and TEM are used to study porosity and pore size distribution while contact angle, XPS and zeta potential are used to investigate surface chemistry of the nucleants. These functionalised 3D nanotemplates are hereby reported to produce protein crystals (concanavalin A and catalase) of different habits without changing any other crystallisation parameters other than the surface chemistry of the templates. This emphasises the potential of 3D nanotemplates with well-ordered porosity and chemistry for further development in protein crystallisation experiments.
Parambil JV, Poornachary SK, Hinder SJ, et al., 2015, Establishing template-induced polymorphic domains for API crystallisation: the case of carbamazepine, CRYSTENGCOMM, Vol: 17, Pages: 6384-6392, ISSN: 1466-8033
Heng J, 2015, Preface, ISBN: 9783319202051
Hedberg S, Heng JYY, Williams DR, et al., 2015, Chromatographic tools to predict the stability of mAbs for faster identification of therapeutic candidates, Pages: 1150-1151
© Copyright American Institute of Chemical Engineers. All rights reserved. Protein-protein molecular interactions are known to be involved in protein solution aggregation behaviour and are a common issue for the manufacturing of therapeutic proteins such as mAbs. Much effort has been employed to gain a better understanding of aggregation, however the mechanisms leading to protein aggregation are still not fully understood. The osmotic second virial coefficient (B22) is a fundamental physiochemical property that describes protein-protein interactions solution, which can be a useful tool to predict aggregation propensity of proteins. One way of predicting aggregation propensity is self-interaction chromatography (SIC), which recently have shown to be a promising tool for better understanding of phase behaviour of proteins. Another technique, cross-interaction chromatography (CIC), has shown to be an even more high-throughput technique than its predecessor with possibly the same capabilities. This work consists of two experimental studies with therapeutic mAbs to improve SIC and CIC as a tool to predict protein aggregation. The first part includes a 10 times scale-down study of therapeutic mAbs from laboratory scale macro-columns to micro-scale columns, which will enable the determination of B22 for the individual protein as well as the cross-virial coefficient, B23, between two proteins. Micro SIC and CIC uses only a few milligrams of mAb in order to obtain a complete formulation study. The results from the first part of the study proved to give good comparable results between the micro and macro scales enabling the use of micro SIC for B22 determinations. The second part of this work presents an extensive formulation study of mAbs, varying pH and salt, as well as the presence of different stabilisers as well as different external factors known to induce aggregation. The B22 and B23 values determined from the formulation study are then correlated with aggregation
Wang D, Da Z, Zhang B, et al., 2015, Stability study of tubular DNA origami in the presence of protein crystallisation buffer, RSC ADVANCES, Vol: 5, Pages: 58734-58737, ISSN: 2046-2069
Shah UV, Olusanmi D, Narang AS, et al., 2015, Decoupling the Contribution of Surface Energy and Surface Area on the Cohesion of Pharmaceutical Powders, Pharmaceutical Research, Vol: 32, Pages: 248-259, ISSN: 1573-904X
PurposeSurface area and surface energy of pharmaceutical powders are affected by milling and may influence formulation, performance and handling. This study aims to decouple the contribution of surface area and surface energy, and to quantify each of these factors, on cohesion.MethodsMefenamic acid was processed by cryogenic milling. Surface energy heterogeneity was determined using a Surface Energy Analyser (SEA) and cohesion measured using a uniaxial compression test. To decouple the surface area and surface energy contributions, milled mefenamic acid was “normalised” by silanisation with methyl groups, confirmed using X-ray Photoelectron Spectroscopy.ResultsBoth dispersive and acid–base surface energies were found to increase with increasing milling time. Cohesion was also found to increase with increasing milling time. Silanised mefenamic acid possessed a homogenous surface with a surface energy of 33.1 ± 1.4 mJ/m2 , for all milled samples. The cohesion for silanised mefenamic acid was greatly reduced, and the difference in the cohesion can be attributed solely to the increase in surface area. For mefenamic acid, the contribution from surface energy and surface area on cohesion was quantified to be 57% and 43%, respectively.ConclusionsHere, we report an approach for decoupling and quantifying the contribution from surface area and surface energy on powder cohesion.
Lee K-Y, Blaker JJ, Heng JYY, et al., 2014, pH-triggered phase inversion and separation of hydrophobised bacterial cellulose stabilised Pickering emulsions, REACTIVE & FUNCTIONAL POLYMERS, Vol: 85, Pages: 208-213, ISSN: 1381-5148
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