Use of surface energy distributions by inverse gas chromatography to understand mechanofusion processing and functionality of lactose coated with magnesium stearate

https://doi.org/10.1016/j.ejps.2011.05.012Get rights and content

Abstract

The purpose was to employ a new finite dilution approach to determine total surface energy distributions of mechanofused powders by inverse gas chromatography (IGC) to contribute to the understanding of their improved flow properties and to help optimise the magnesium stearate (MgSt) coating. Pharmatose 450M was mechanofused with between 0.1 and 8% (w/w) of MgSt. The non-polar, polar and total surface energies and work of cohesion at infinite dilution and the energy distributions at finite dilution were constructed using IGC. Brunauer–Emmet–Teller (BET) surface area and particle morphology were determined by IGC and scanning electron microscope, respectively. Surface energies determined at finite dilution appeared more consistent with the observed flow behaviour of mechanofused powders than comparative surface energy determination at infinite dilution. Polar and total surface energy distributions together with BET surface area measurements were the lowest when lactose was mechanofused with 1–2% MgSt (w/w). In conclusion, the surface energy distribution profiles measured at finite dilution were argued to be more informative and useful in reporting the surface energy changes during mechanofusion, optimising MgSt concentration in the mechanofusion process, and the flow behaviour of mechanofused powders.

Introduction

Surface energy (γ), a combination of non-polar (γNP) and polar components (γP), is the measure of excess energy that exists on the surface of a material (Van Oss et al., 1988, Grimsey et al., 2002). Inverse gas chromatography (IGC) has been widely used to characterise the surface energy of materials in the pharmaceutical industry (Grimsey et al., 2002). In IGC, different probes are passed through a column filled with the solid material under investigation. Surface energy is calculated from the free energy of adsorption for interaction of probe molecules with the material surfaces. The interaction is physical; however, it is influenced by the chemical environment such as the presence of different atoms or chemical groups that exist on the material surface. For example, if a material contains non-polar groups on the surface, the non-polar surface energy tends to be high. Alternatively, a material surface rich in polar groups or dipoles on the surface tends to have a high polar surface energy. The polar surface energy has both acidic (γ+) and basic (γ) components (van Oss et al., 1988). Any change in the surface chemical environment will lead to a change in surface energy which may influence the interactions within, and hence bulk properties of a powder.

Mechanofusion is a term used for a range of intensive mechanical dry coating processes that are designed to deposit a thin coating of a material onto a solid surface through high compression and shear and hence can be used to alter the surface characteristics of a material without using any solvent (Pfeffer et al., 2001). In recent times, the approach has been of interest to pharmaceutical scientists, especially in engineering suitable flow, fluidisation and aerosolisation characteristics into powders from otherwise cohesive materials. Magnesium stearate (MgSt) has been predominantly used as a coating material although mechanofusion has been also conducted with other materials such as fumed silica and alumina (Ramlakhan et al., 2000, Yang et al., 2005, Briones-Rodriguez et al., 2007). During the mechanofusion process, a very thin coating, proposed to be as thin as 10 nm or less, is left on the surface of the host material (Yang et al., 2005, Green et al., 2009, Zhou et al., 2010a). The flow of a lactose powder has been shown to improve dramatically following mechanofusion with MgSt (Zhou et al., 2010a, Zhou et al., 2010b, Zhou et al., 2010c, Zhou et al., 2010d). These studies also revealed a decrease in cohesive interactions using a shear cell of the Freeman Technology, FT4 powder rheometer. As the adhesive/cohesive forces or inter-particular interactions are directly proportional to surface energy (Johnson et al., 1971, Derjaguin et al., 1978), one would expect the surface energy of lactose powders to decrease after mechanofusion with MgSt.

However, an increase in non-polar surface energy at infinite dilution measured using IGC after coating lactose with MgSt was found (Kumon et al., 2006, Kumon et al., 2008). This observation was not consistent with the studies of Zhou et al. (2010a) who found reduced cohesive/adhesive forces and improved flow properties and dispersibility. As the total surface energy encompasses both non-polar and polar surface energies, the determination of total surface energy (Thielmann et al., 2003, Traini et al., 2008) at infinite dilution might be more appropriate for understanding the behaviour of mechanofused lactose than relating to only non-polar surface energy. Moreover, the surface energy of mechanofused materials may vary regionally on the surface based on the orientation of different surface groups on different parts of the surface. The concentration of coating material may also influence the surface energy as the uniformity and thickness of the film will depend on the amount of coating material used during the mechanofusion process. In addition, any uncoated region may have a different surface energy compared to that of the coated region. Since the surface energy measurement at infinite dilution involves interactions with only the highest energy sites, which may not represent the surface energy status of the whole surface (Yla-Maihaniemi et al., 2008), the determination of total surface energy distribution using a finite dilution approach (Das et al., 2011) may be the preferred approach for understanding the bulk flow behaviour of mechanofused materials. The finite dilution approach involves not only interactions of the probes with the highest energy sites, but also interactions with less energetic sites. The non-polar surface energy distribution method is already established (Thielmann et al., 2007, Yla-Maihaniemi et al., 2008, Ho et al., 2010). However, for complete characterisation, the polar surface energy distributions must also be known to allow the total surface energy distributions to be obtained. A method to determine the polar surface energy distribution profiles has been documented recently and will be utilised here to obtain the total surface energy distribution profiles (Das et al., 2011). Therefore, the purpose of the project was to determine the potential advantages of surface energy distribution measurements in optimising the concentration of MgSt used to coat a model excipient, lactose, and in understanding the functionality of the mechanofused powders. The non-polar, polar and total surface energies were determined at infinite and finite dilution, and the work of cohesion was calculated.

Section snippets

Materials

α-Lactose monohydrate, Pharmatose®450M (Ptos), used in this study was received from DMV International (Veghel, The Netherlands) as a donation. Magnesium stearate (MgSt) was supplied by Mallinckrodt Baker, Inc. (Phillipsburg, NJ, USA). GC grade heptane, octane, nonane, decane (all from Sigma–Aldrich GmbH, Steinheim, Germany); methane, helium and air (all from Core Gas Pty. Ltd., NSW, Australia) were used in the IGC experiments.

Mechanical dry coating

α-Lactose monohydrate (5 g) was dry coated with 0%, 0.1%, 1%, 2%, 5%

Morphological change on the surface

In order to examine the changes in surface morphology of Ptos before and after mechanofusion with different concentrations of magnesium stearate, scanning electron micrographs were taken of all the powders (Fig. 1). Flat and smooth surfaces with sharp edges were clearly seen in SEM of unprocessed Ptos (Fig. 1A). Some small particles were observed to adhere onto the surface of larger particles or to exist as agglomerates. Magnesium stearate particles were small (5–10 μm size) and existed as

Surface energy of mechanofused lactose

The non-polar surface energy of MgSt, determined at infinite dilution, was significantly lower than Ptos or any of the MgSt coated Ptos powders. However, the non-polar surface energy of coated Ptos at infinite dilution significantly increased after mechanofusion achieving a maximum value for Ptos-2%MgSt (Fig. 3A). This trend was difficult to understand unless the deposition of MgSt caused by the compression and shear of the mechanofusion process changed the structure or orientation of the

Conclusion

This research has shown the advantages of the use of surface energy profiles in optimising the concentration of MgSt used in mechanofusion and in interpreting flow and bulk behaviours of coated lactose. The use of infinite dilution surface energy measurements can be problematic because of the limited surface energy information it produces which relate to only a fraction of the surface of the coated material and to its highest energy sites. In particular, in this research, the measurement of

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