effects of interactions between powder particle size and binder viscosity on agglomerate growth...
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European Journal of Pharmaceutical Sciences 12 (2001) 297309www.elsevier.nl / locate /ejps
Effects of interactions between powder particle size and binder viscosityon agglomerate growth mechanisms in a high shear mixer
*Anita Johansen, Torben SchferThe Royal Danish School of Pharmacy, Department of Pharmaceutics, 2 Universitetsparken, DK-2100 Copenhagen, Denmark
Received 3 July 2000; received in revised form 5 September 2000; accepted 12 September 2000
A study was performed in order to elucidate the effects of the interactions between powder particle size and binder viscosity on themechanisms involved in agglomerate formation and growth. Calcium carbonates having mean particle sizes in the range of 5214 mm andpolyethylene glycols having viscosities in the range of approximately 50100 000 mPas were melt agglomerated in a high shear mixer.Agglomerate growth by nucleation and coalescence was found to dominate when agglomerating small powder particles and binders with alow viscosity. Increasing the binder viscosity increased the formation of agglomerates by immersion of powder particles in the surface ofthe binder droplets. With a larger powder particle size, an increasing binder viscosity was necessary in order to obtain an agglomeratestrength being sufficient to avoid breakage. Due to a low agglomerate strength, a satisfying agglomeration of very large particles (214mm) could not be obtained, even with very viscous binders. The study demonstrated that the optimum agglomerate growth occurred whenthe agglomerates were of an intermediate strength causing an intermediate deformability of the agglomerates. In order to producespherical agglomerates (pellets), a low viscosity binder has to be chosen when agglomerating a powder with a small particle size, and ahigh viscosity binder must be applied in agglomeration of powders with large particles. 2001 Elsevier Science B.V. All rightsreserved.
Keywords: Melt agglomeration; High shear mixer; Binder viscosity; Powder particle size; Polyethylene glycols; Agglomerate growth mechanisms
1. Introduction is distributed on the surface of the powder particles, andformation of nuclei occurs by coalescence between the
Agglomeration is an important and established technolo- wetted particles. By the immersion mechanism, nuclei aregy in many industrial processes. However, the knowledge formed when the powder particles are captured on theof the mechanisms and kinetics involved in agglomeration surface of the binder droplets and immersed. When theis still sparse, and the need of additional research in the binder droplet size is larger than the size of the powdermatter is evident. particles, the dominating agglomerate formation mecha-
Some of the important early contributions to theory on nism will tend to be the immersion mechanism. In a highagglomeration were made by Newitt and Conway-Jones shear mixer, the binder droplet size will normally become(1958), Rumpf (1962), Capes and Danckwerts (1965), and reduced by comminution in the initial stage of the processKapur (1978). More recently, Ennis et al. (1991) de- because of the shearing forces. A low binder viscosity willveloped a new agglomeration model, and this work has enhance this size reduction of the binder droplets, as will abeen followed by several other investigations into ag- higher impeller speed. Therefore, a small initial binderglomeration mechanisms and kinetics (Knight, 1993; Kris- particle size, a low binder viscosity, and/or a high impellertensen, 1996; Iveson et al., 1996; Tardos et al., 1997; speed promote the distribution mechanism. On the otherHoornaert et al., 1998; Iveson and Litster, 1998). hand, a large initial binder particle size, a high binder
In melt agglomeration, the formation of agglomerates viscosity, and/or a low impeller speed promote the immer-can proceed by two different mechanisms (Schfer and sion mechanism (Schfer and Mathiesen, 1996a).Mathiesen, 1996a). By the distribution mechanism, binder The nuclei formed initially in the process might grow in
size by coalescence between nuclei. This agglomerategrowth is determined by a balance between coalescence*Corresponding author. Tel.: 145-35-306-000; fax: 145-35-306-031.
E-mail address: firstname.lastname@example.org (T. Schfer). and breakage. Coalescence will be the dominant growth
0928-0987/01/$ see front matter 2001 Elsevier Science B.V. All rights reserved.PI I : S0928-0987( 00 )00182-2
298 A. Johansen, T. Schfer / European Journal of Pharmaceutical Sciences 12 (2001) 297 309
mechanism if the agglomerates possess a high agglomerate Powder particles that are too large will result in a wide sizestrength (Tardos et al., 1997). If the agglomerates are too distribution and agglomerates with a non-uniform shapeweak to resist the impact and shearing forces in the mixer, due to breakage. The optimum particle size of a rawa marked agglomerate breakage will occur simultaneously material to be melt pelletized has been indicated to be inwith growth by coalescence (Knight et al., 1998; Eliasen et the size range of 2025 mm (Schfer et al., 1992b).al., 1998, 1999). As a result, particles and small fragments Keningley et al. (1997) have shown that to formformed by breakage might participate in the growth by a granules with calcium carbonate and silicone oils, alayering mechanism by which small particles or fragments minimum binder viscosity was required, which increasedare layered on the surface of surviving agglomerates with the size of the powder particles from 1 mPas with(Linkson et al., 1973; Eliasen et al., 1999). 8-mm particles to 1 Pas with 230-mm particles. This
The agglomerate strength becomes increased by a indicates that an interaction between powder particle sizesmaller powder particle size, a higher binder viscosity, and and binder viscosity might be important in order to controlby a densification of the agglomerates (Kristensen et al., the agglomerate growth. The present work is based on the1985a; Keningley et al., 1997). In a high shear mixer, the hypothesis that a controllable agglomerate growth isshearing forces become increased by a higher impeller attainable with powders having a small as well as a largerotation speed. Further, the shearing forces depend on the particle size by combining the powder particle size and thesize and shape of the impeller blades (Schfer et al., binder viscosity in a way that gives rise to a suitable1993b). agglomerate strength. The purpose of this work is to test
According to Ennis et al. (1991), growth by coalescence this hypothesis by carrying out melt agglomeration experi-occurs until a critical agglomerate size has been reached. ments in a high shear mixer.This critical size becomes increased by, e.g., a smaller sizeof the powder particles /agglomerates, a higher binderviscosity, and a lower impeller speed (Ennis et al., 1991; 2. Materials and methodsTardos et al., 1997). However, at the same time a higherviscosity will reduce the growth potential by decreasing 2.1. Materialsthe deformability and the rate of densification of theagglomerates. The effect of viscosity on agglomerate Six different grades of calcium carbonate powders withgrowth will therefore depend on the balance of these two different mean particle size, manufactured from a whitecounteracting effects (Schfer and Mathiesen, 1996c). marble, and produced by comminution and classificationAgglomerates can only resist deformation and breakage (Omya, France), were used as starting material. Poly-when below a critical agglomerate size, which depends on ethylene glycol (PEG) 1500 S, 3000 S, 6000 S, 10000 S,the externally applied energy and on the agglomerate 20000 S, or 35000 S (Hoechst, Germany) was used asstrength (Tardos et al., 1997). meltable binder. S indicates that the PEGs are used as
Agglomeration of powders with a mean particle size flakes. Butylated hydroxyanisole (BHA) (Merck-Schuch-below approximately 10 mm has traditionally been trouble- ardt, Germany) was used as an antioxidant in order tosome and has often led to an uncontrollable agglomerate prevent thermal decomposition of the binder during thegrowth. This is because of the high liquid saturation agglomeration process (Schfer and Mathiesen, 1996b).needed in order to obtain a sufficient deformability to The size distribution by volume of the calcium carbon-counteract for the high agglomerate strength caused by the ates was determined by a Malvern 2601Lc laser diffractioncohesiveness of the small particles (Schfer et al., 1992b; particle sizer (Malvern Instruments, UK). The span isSchfer, 1996a; Schfer and Mathiesen, 1996b; Knight et calculated as the difference between the diameters at 90al., 1998). Also, the agglomeration of large powder and 10 percentage points relative to the median diameter,particles is problematic. Breakage will often dominate, and D(v;0.5).no agglomeration can occur because of a low agglomerate A Gemini 2375 Surface Area Analyzer (Micromeritics,strength (Newitt and Conway-Jones, 1958; Capes and USA) was used for the determination of the BET multi-Danckwerts, 1965). In melt agglomeration experiments, it point surface area of the calcium carbonates.has previously been shown that a powder with a mean The true density of the calcium carbonates and of theparticle size of 100 mm was unable to agglomerate solid PEGs was determined by an Accupyc 1330 gas(Thomsen, 1994). In agglomeration experiments with a displacement pycnometer (Micromeritics, USA) usingcoarse lactose monohydrate (127 mm) agglomerated with helium purge. The poured and tapped densities of thewater, weak granules were produced (Mackaplow et al., calcium carbonates were determined according to the test2000). for apparent volume (European Pharmacopoeia, 1999), and
The powder particle size is especially critical if pellets the interparticular porosities were calculated from thehave to be prod