Effect of mechanical dry particle coating on the improvement of powder flowability for lactose monohydrate: A model cohesive pharmaceutical powder Qi (Tony) Zhou, Li Qu, Ian Larson, Peter J. Stewart, David A.V. Morton ⁎ Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia abstract article info Article history: Received 27 June 2010 Received in revised form 12 October 2010 Accepted 20 November 2010 Available online 27 November 2010 Keywords: Mechanical dry coating Mechanofusion Lactose Cohesive powder Powder flowability The aim of this study was to evaluate the effect of an intensive dry coating process on the improvement in flow behaviours for fine cohesive lactose powders as a function of size distribution and coating process parameters. Various commercial fine lactose powders with particle size range from approximately 4 to 120 μm were dry coated with magnesium stearate using a recently optimised mechanofusion approach. The bulk densities for all cohesive powders increased and flow behaviours were improved substantially except for the already free- flowing powder of R010 (with VMD approximately 120 μm). Of particular note, the originally non-flowing cohesive powder P450 with VMD approximately 20 μm achieved free-flowing characteristics and was as flowable as R010 after mechanofusion. The improvement in powder flow behaviours was shown to be dependent on coating parameters such as coating speed and coating time duration. At an appropriate coating speed, optimal coating can be achieved after processing for 5 min for P450. This study demonstrated that an optimised mechanofusion process is an efficient and effective approach for substantially improving flow of fine cohesive powders to achieve equivalent flow behaviours of much larger sized powders. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Particulate handling plays a fundamental part in industrial manufacturing operations [1]. In pharmaceutical and related indus- tries, 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 formula- tions. 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 b 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 mechanofu- sion for different materials and process geometries appears complex and is not well understood [8–10]. However, unlike conventional milling and co-milling processes, the energy input in a mechanofusion Powder Technology 207 (2011) 414–421 ⁎ Corresponding author. Tel.: + 61 3 9903 9523; fax: + 61 3 9903 9583. E-mail address: david.morton@pharm.monash.edu.au (D.A.V. Morton). 0032-5910/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.powtec.2010.11.028 Contents lists available at ScienceDirect Powder Technology journal homepage: www.elsevier.com/locate/powtec