Tribo-electric Charging and Adhesion of Cellulose Ethers and their Mixtures with Flurbiprofen

The pervasiveness of tribo-electric charge during pharmaceutical processing can lead to the exacerbation of a range of problems including segregation, content heterogeneity and particle surface adhesion. The excipients, hydroxypropyl methylcellulose and methylcellulose, are often used in drug delivery systems and so it is important to understand the impact of associated factors on their charging and adhesion mechanisms, however, little work has been done. Such phenomena become more prominent when excipients are introduced to a powder mixture alongside the active pharmaceutical ingredient(s) (APIs) with inter- and intra-particulate interactions giving rise to electrification and surface adhesion of powder particles. The aim of this study was to understand the impact of material attributes (particle size, hydroxypropyl (Hpo) to methoxyl (Meo) ratio and molecular size) on the charging and adhesion characteristics of cellulose ethers. Furthermore, poorly compactible and highly electrostatically charged drug, flurbiprofen, was used to develop binary powder mixtures having different polymer to drug levels. Subsequently, a relationship between tribo-electric charging and surface adhesion was studied. Charge was induced on powder particles and measured using a custom built device based on a shaking concept consisting of a Faraday cup connected to electrometer. The diversity in physicochemical properties has shown a significant impact on the tribo-electric charging and adhesion behaviour of MC and HPMC. Moreover, the adhesion and electrostatic charge of the API was significantly reduced when MC and HPMC were incorporated. Moreover, tribo-electric charging shows a linear relationship (R2= 0.81-0.98) with particle surface adhesion, however, other factors were also involved. It is anticipated that such reduction in charge and particle surface adhesion would improve flow and compaction properties during processing

Tribo-electrification and Powder Adhesion Studies in the Development of Polymeric Hydrophilic Drug Matrices

The generation of tribo-electric charge during pharmaceutical powder processing can cause a range of complications, including segregation of components leading to content uniformity and particle surface adhesion. This phenomenon becomes problematical when excipients are introduced to a powder mixture alongside the highly charging active pharmaceutical ingredient(s) (APIs). The aim of this study was to investigate the tribo-electric charging and adhesion properties of a model drug, theophylline. Moreover, binary powder mixtures of theophylline with methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC), having different polymer to drug ratios, were formed in order to study the impact of polymer concentration, particle size, substitution ratio and molecular size on the tribo-electric charging and surface adhesion properties of the drug. Furthermore, the relationship between tribo-electric charging and surface adhesion was also studied. The diversity in physicochemical properties of MC/HPMC has shown a significant impact on the tribo-electric charging and adhesion behaviour of theophylline. It was found that the magnitude of electrostatic charge and the level of surface adhesion of the API were significantly reduced with an increase in MC and HPMC concentration, substitution ratios and molecular size. In addition, the tribo-electric charge showed a linear relationship with particle surface adhesion, but the involvement of other forces cannot be neglected

Using small-angle X-ray scattering to investigate the compaction behaviour of a granulated clay

The compaction behaviour of a commercial granulated clay (magnesium aluminium smectite, gMgSm) was investigated using macroscopic pressure-density measurements, X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray microtomography (XμT) and small-angle X-ray scattering (SAXS). This material was studied as a potential compaction excipient for pharmaceutical tabletting, but also as a model system demonstrating the capabilities of SAXS for investigating compaction in other situations. Bulk compaction measurements showed that the gMgSm was more difficult to compact than polymeric pharmaceutical excipients such as spheronised microcrystalline cellulose (sMCC), corresponding to harder granules. Moreover, in spite of using lubrication (magnesium stearate) on the tooling surfaces, rather high ejection forces were observed, which may cause problems during commercial tabletting, requiring further amelioration. Although the compacted gMgSm specimens were more porous, however, they still exhibited acceptable cohesive strengths, comparable to sMCC. Hence, there may be scope for using granular clay as one component of a tabletting formulation. Following principles established in previous work, SAXS revealed information concerning the intragranular structure of the gMgSm and its response to compaction. The results showed that little compression of the intragranular morphology occurred below a relative density of 0 · 6, suggesting that granule rearrangements or fragmentation were the dominant mechanisms during this stage. By contrast, granule deformation became considerably more important at higher relative density, which also coincided with a significant increase in the cohesive strength of compacted specimens. Spatially-resolved SAXS data was also used to investigate local variations in compaction behaviour within specimens of different shape. The results revealed the expected patterns of density variations within flat-faced cylindrical specimens. Significant variations in density, the magnitude of compressive strain and principal strain direction were also revealed in the vicinity of a debossed feature (a diametral notch) and within bi-convex specimens. The variations in compaction around the debossed notch, with a small region of high density below and low density along the flanks, appeared to be responsible for extensive cracking, which could also cause problems in commercial tabletting

Segregation of Formulated Bulk Powders due to Electrostatic Effects

Particle electrification is a common phenomenon that occurs in many powder handling industries such as pharmaceuticals and detergents etc. The unit operations involved in the manufacture of pharmaceutical formulations frequently subject particles to frictional sliding and impact against processing surfaces, giving rise to tribo-electric charging. Pharmaceutical materials, in particular, are susceptible to electrostatic charging due to their low bulk density, small particle size and often irregular shape and electrically insulating nature. The electrostatic charge may cause particles to adhere to container surfaces leading to a loss of powder through deposition; however the problem often extends further and affects the end products’ quality. Segregation can also occur when powders have been subjected to tribo-electrification. In this paper we investigate whether such adhesion resulting from the electrostatic charging could give rise to the segregation of components within a binary mixture. Binary mixtures comprising of α-lactose monohydrate (α-LM) and hydroxypropyl cellulose (HPC) were firstly tribo-charged and then the wall adhered particles were separated by a selective dissolution of one component and the filtration of the non-dissolving component, followed by a gravimetric analysis. The findings reveal that a considerable level of segregation can take place on the wall-adhered particles

Tribo-Electrification and Associated Segregation of Formulated Bulk Powders

Powder handling operations can give rise to the electrification of particles therein, causing particles to adhere to the walls of processing equipment. This can lead to a loss of powder through deposition; however the problem often extends further and affects the end products’ quality. Segregation can also occur when powders have been subjected to tribo-electrification. The existing literature reveals that the few methods that are available to predict the dynamic charging of bulk powders are unsuitable for testing/handling small quantities of powders, some of which are highly active. Furthermore, very little work has been reported on the effect of triboelectrification on the segregation of components of mixtures. The objective of this work is to develop a methodology for investigating the triboelectrification of small quantities of bulk powders through the adaptation of a Retsch® shaking device, with the aim of characterising two common pharmaceutical excipients; namely alpha-lactose monohydrate (a-LM) and hydroxypropyl cellulose (HPC). The electric charge transferred to the particles has been quantified as a function of shaking time, frequency and container material. The temporal trend follows a first order rate process. Using numerical simulation based on Distinct Element Modelling, the transient charge accumulation of an assemblage of alumina beads inside the shaking device was predicted based on the single particle contact charge obtained from the experiments. It is shown that the inclusion of electrostatic parameters into the DEM model leads to an acceptable prediction of the charge build-up. Binary mixtures comprising of a-LM and HPC were firstly tribo-charged and then the wall adhered particles were separated by a selective dissolution of one component and the filtration of the non-dissolving component, followed by a gravimetric analysis. The findings reveal that a considerable level of segregation can take place on the wall-adhered particles. The methodology developed in this work has the potential to be used to characterise small quantities of pharmaceutical powders including active pharmaceutical ingredients (API), which are sparse in the early development stages

An analysis of a simple test device for tribo-charging of bulk powders

A simple device for characterisation of the tribo-charging propensity of powders has been developed at the University of Leeds, where a small amount of powder is placed inside a 10 ml container, which is shaken by reciprocal strokes in a horizontal direction. Several containers with different materials have been made: stainless steel, polytetrafluoroethylene (PTFE) and glass. The charge on the powder is measured using a Faraday cup connected to an electrometer. The charge is measured before and after the shaking process. The main objective of this work is to analyse the operation of this simple test device by investigating the behaviour of α-lactose monohydrate, hydroxy propyl cellulose (HPC) and a 50:50 binary mixture (by mass) of these two powders with various surfaces that are most commonly used in the pharmaceutical industry. The experiments are carried out in controlled environmental conditions and using different shaking times together with different shaking frequencies of 10, 20 and 30 Hz. The experimental results show that -lactose monohydrate and HPC particles have the highest magnitude of charge at 20 Hz frequency against all surfaces tested. This is surprising, as it is intuitively expected that higher charges should be produced at 30 Hz, given other conditions. The dynamic movement of particles within a shaking container vary with frequency. This results in a varied amount of particle-wall contacts which affects particle charging

Electrostatic Charge Generation due to Shear Deformation of Pharmaceutical Powders

In powder handling operations, such as mixing, conveying, sieving and milling, particles frequently make contact with each other and the walls of the processing equipment. During these interactions, the electrification of particles takes place, commonly known as tribocharging. This paper focuses on investigating the tribocharging characteristics of bulk powders under shear deformation. In particular, the effect of shear strain and shear rate on the charge generation is analysed. An annular shear cell, modified for electrostatic charging, is used for applying a shear strain to a bed of pharmaceutical powders. α-lactose monohydrate particles, widely used as an excipient for pharmaceutical formulations, is used as a model system. It is shown that the charge on the particles increases with the applied shear strain

The influence of salt formation on electrostatic and compression properties of flurbiprofen salts

Salt formation is an effective method of improving physicochemical properties of acidic and basic drugs. The selection of a salt form most suitable for drug development requires a well-designed screening strategy to ensure various issues are addressed in the early development stages. Triboelectrification of pharmaceutical powders may cause problems during processing such as segregation of components due to the effects of particle adhesion. However, very little work has been done on the effect of salt formation on triboelectrification properties. In this paper, salts of flurbiprofen were prepared by combining the drug with a selection of closely related amine counter ions. The aim of the work was to investigate the impact of the counter ion on electrostatic charge of the resultant salts to inform the salt selection process. The experimental results show the magnitude of charge and polarity of the flurbiprofen salts to be highly dependent on the type of counter ion selected for the salt formation. Furthermore, particle adhesion to the stainless steel surface of the shaking container and the salts’ compression properties were measured. The formed salts had lower electrostatic charges, improved tabletability, and resulted in reduced adhesion of these powders compared with the parent drug

Tribo-Electrification and Associated Segregation of Pharmaceutical Bulk Powders

Powder handling operations can give rise to the tribo-electrification of particles, causing a number of problems such as risk of fire and explosion, particle adhesion to the walls of processing equipment and segregation. Current methods available for measuring the dynamic charging of bulk powders are unsuitable for testing/handling small quantities of powders, some of which are highly active. Furthermore, very little work has been reported on the effect of tribo-electrification on the segregation of components of mixtures. A methodology has recently been developed for investigating the tribo-electrification of small quantities of bulk powders using a shaking device. Two common pharmaceutical excipients, namely α -lactose monohydrate (α -LM) and hydroxypropyl cellulose (HPC) were used as model materials. The electric charge transferred to the particles was quantified as a function of shaking time,frequency and container material. The temporal trend follows a first-order rate process. Using numerical simulations based on the Distinct Element Method (DEM), the charge accumulation of an assemblage of alumina beads inside the shaking device was analysed based on the single particle contact charge obtained from the experiments. It was shown that the inclusion of electrostatic mechanisms into the DEM model leads to an improved prediction of the charge buildup, but the difference with experimental data is still notable. Using the above method, segregation induced by tribo-electric charging was characterised for binary mixtures comprising α -LM and HPC. The bulk and wall-adhered particles were analysed for the mass fraction of each component using selective dissolution of one component and filtration of the non-dissolving component, followed by a gravimetric analysis. The findings reveal that a considerable level of segregation can take place on the wall-adhered particles. The method described here has the potential to be used to characterise small quantities of pharmaceutical powders including active pharmaceutical ingredients (API), which are sparse in the early development stages