Effect of mechanical dry particle coating on the improvement of powder flowability for lactose monohydrate: A model cohesive pharmaceutical powder
Graphical Abstract
A series of eight lactose powders ranging in VMD from 4 to 120 μm were dry coated with magnesium stearate using a mechanofusion approach. Both traditional flow indices and shear measurements demonstrated substantial improvements in flowability after mechanofusion, such that initially cohesive powders at sizes as small as 20 μm became free-flowing.
Research Highlights
►Mechanofusion with magnesium stearate improved flow of cohesive lactose powders. ►The improvement in powder flow was dependent on coating parameters. ►Optimal coating can be achieved after processing for 5 min. ►Mechanofusion is an efficient and effective approach for improving powder flow.
Introduction
Particulate handling plays a fundamental part in industrial manufacturing operations [1]. In pharmaceutical and related industries, product performance is often based on powder flow or de-agglomeration behaviours, where fine cohesive powder is common: for example, to fill a tablet die, to fluidise in a coater, to empty a sachet, or to re-suspend a powder from an inhaler [2]. Notably, powder flowability is highly influential and often the major issue with particulate handling and processing. Handling cohesive powder containing fine particles is a generic industrial problem since such powders exhibit poor flowability due to the strong inter-particle attractive forces associated with small particle sizes [3].
Besides aeration and vibration, addition of glidants is a common approach used to improve the flow of solid formulations. Fumed silica is probably the most widely used glidant in pharmaceutical formulations. It is believed to act as guest particles on the surface of host particles which then reduces cohesive and frictional forces between host particles [4]. This approach can improve powder flow for some cohesive powders. However, such glidant particles with very small particle sizes (typically < 1 μm) tend to have poor flow themselves and can be difficult to readily disperse onto host particle surfaces uniformly [5], especially, for fine host particles smaller than 50 μm which commonly form strongly agglomerated structures. In such cases, conventional mixing may not provide enough energy to break the host particle agglomerates and expose host particle surfaces to glidant guest particles. Hence, glidant is difficult to deposit and disperse onto individual host particle surfaces [6]. Recently, selected dry coating techniques have been used to improve the flowability of cohesive powders by modifying their inter-particulate interactions. In general, dry coating is an attractive approach, as it is simpler, cheaper, safer and more environment-friendly than solvent-based alternatives [7]. “Mechanofusion” is a term used for intensive dry coating approaches that have gained interest for particle and powder modification [8].
A number of different mechanofusion systems are available, but in general they consist of a cylindrical chamber and a process head which rotate relative to each other at high speed to create intense shear and compression of the core (host) and coating (guest) particles both via impaction with the face of the process head and via compression as the particles are pushed between the edge of the head and the inner chamber wall. The process head should consequently break up agglomerates of the cohesive particles to expose their surfaces. The process head rotates at high speed so that a considerable amount of thermo-mechanical energy is generated which coats the guest material onto the exposed surfaces of the host particles [9]. Although the particle interactions and kinetic energy exchanges in the mechanofusion process have been studied using simulation and modelling tools, the mechanism of mechanofusion for different materials and process geometries appears complex and is not well understood [8], [9], [10]. However, unlike conventional milling and co-milling processes, the energy input in a mechanofusion process is more tightly controlled because the process head geometry, speed and gap from the wall are fixed. Consequently the energy of collision and compression is more specifically tailored. The process can thus be tuned to encourage coating but not size reduction [11].
Flow of some poor-flowing powders has been reported to be improved dramatically after mechanofusion. For example, 5 μm polymethylmethacrylate (PMMA) particles coated with 10% (w/w) of 0.015 μm TiO2 particles using a mechanofusion process was reported to flow so freely that it appeared to possess a near-zero angle of repose (AOR). In contrast, both the original PMMA and TiO2 particles had poor flow properties [12]. Similar findings are also reported when micron-sized PMMA was mechanofused with nano-sized TiO2, Al2O3, or SiO2 particles [13]. Processing of ground polystyrene resin of 10 μm size with carbon black via mechanofusion was also demonstrated to produce easily flowing toner material of rounded shape [12]. Dry coating of corn starch with different silica particles also showed a dramatic improvement in powder flow reflected by lower angle of repose values, and achieved better dispersion of silica particles on the corn starch particle surfaces [5]. In our earlier investigations, powder flow characteristics have been improved significantly after a mechanofusion treatment of a cohesive lactose monohydrate powder (median particle size of approximately 20 μm). It also showed that the lactose powders coated with magnesium strearate achieved much greater improvements in flow than those coated with fumed silica [6].
In this study, the effect of host particle size, processor rotation speed and processing time on the improvement of flow on lactose powders was investigated in detail to provide a unique view on benefits of optimization of such intensive dry surface coating process. Lactose was selected as a model material as it is known to exist as cohesive fine powders which are commonly used in pharmaceutical applications. Flow behaviours were characterized using traditional Carr index and a shear testing approach.
Section snippets
Materials
Commercially available lactose monohydrate samples were used in this study. Pharmatose® 450 M (P450) and Pharmatose® 350 M (P350), Pharmatose® 200 M (P200), Respitose® SV003 (R003), Respitose® SV010 (R010) were donated by DMV International, Veghel, The Netherlands. Sorbalac® 400 (S400) was obtained from Meggle GmbH, Wasserburg, Germany and Lactohale® LH 300 (L300) from Friesland Foods Domo, Zwolle, The Netherlands. Magnesium stearate NF (MgSt) was supplied by Mallinckrodt Chemicals, Phillipsburg,
SEM
Representative SEM micrographs of the untreated and mechanofused S400, P450 and R003 are shown in Fig. 2. Images of S400, P450 and R003 were chosen to demonstrate the morphological properties of relative small, medium and large groups in this series of lactose powders respectively. All untreated lactose particles exhibited similar irregularly angular or elongated shapes. After mechanofusion, no substantial changes in gross particle shape can be observed for all lactose samples. However, what
Discussion
These results systematically demonstrated how powder flow indicators and hence powder structures strongly depend on particle size distribution as well as surface coating quality. It is not surprising that an increase in median particle size can result in better flow because gravitational forces become dominant over cohesive or friction forces in particle interactions in a powder bed for large particles [3]. However, for fine and cohesive powders with particle sizes around 10–20 μm, the
Conclusions
In this study, powder flowability for a series of cohesive lactose powders was substantially improved after mechanofusion with low levels of MgSt. The non-flowing (Geldart group C) cohesive lactose monohydrate powder with a median particle size approximately 20 μm achieved the same free-flowing characteristics as the lactose monohydrate powder with a median particle size approximately 120 μm (Geldart group A) after mechanofusion. Such improvement in powder flow is attributed to the reduction in
Acknowledgements
Thanks to DMV International, Meggle GmbH and Friesland Foods Domo for the kind donation of lactose samples. Thanks to Kerry Cheng and Geoffrey Tan for their assistance in the mechanofusion operation. Qi Tony Zhou would like to acknowledge the scholarship support from Faculty of Pharmacy and Pharmaceutical Sciences, Monash University.
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