Research Paper Effect of Surface Energy on Powder Compactibility Frauke Fichtner, 1 Denny Mahlin, 1,4 Ken Welch, 2 Simon Gaisford, 3 and Göran Alderborn 1 Received March 6, 2008; accepted May 23, 2008; published online June 12, 2008 Purpose. The influence of surface energy on the compactibility of lactose particles has been investigated. Materials and Methods. Three powders were prepared by spray drying lactose solutions without or with low proportions of the surfactant polysorbate 80. Various powder and tablet characterisation procedures were applied. The surface energy of the powders was characterized by Inverse Gas Chromatography and the compressibility of the powders was described by the relationship between tablet porosity and compression pressure. The compactibility of the powders was analyzed by studying the evolution of tablet tensile strength with increasing compaction pressure and porosity. Results. All powders were amorphous and similar in particle size, shape, and surface area. The compressibility of the powders and the microstructure of the formed tablets were equal. However, the compactibility and dispersive surface energy was dependent of the composition of the powders. Conclusion. The decrease in tablet strength correlated to the decrease in powder surface energy at constant tablet porosities. This supports the idea that tablet strength is controlled by formation of intermolecular forces over the areas of contact between the particles and that the strength of these bonding forces is controlled by surface energy which, in turn, can be altered by the presence of surfactants. KEY WORDS: amorphous lactose; powder compactibility; surface energy; surfactant; tablet tensile strength. INTRODUCTION A pharmaceutical tablet has been described in physical terms (1) as a large cluster of particles, held together by bonds active between external particle surfaces, i.e. the particles bind predominantly by particle–particle adsorption. The fracturing of a tablet involves the separation of the external particle surfaces from each other. Thus, the proper- ties of the surface of the particles should have a significant effect on the tensile strength of the tablet. An important example (1) of the role the particle surface for tablet strength is the marked difference in compactibility between a lubri- cated, i.e. a powder for which a lubricant is spread out on the particle surfaces, and a non-lubricated powder. According to continuum fracture mechanics, the tensile strength of a solid is dependent on the microstructure of the solid specimen. The principles of fracture mechanics have been applied to the fracturing of agglomerates and compacts, i.e. porous solid specimens composed of particles surrounded by a network of pores (2–4). In such expressions, the fracture energy of the solid together with the microstructure of the compact (flaw size, agglomerate packing fraction and particle diameter) control agglomerate strength. It is reasonable that the fracture energy will show some proportionality with the surface energy of solids with similar microstructure. Rumpf’s approach (5) to assess tensile strength of agglomerates is based on a bond summation approach, i.e. the strength equates the sum of all inter-particulate forces in the fracture plane (that are separated simultaneously). In case of van der Waals attractions acting between particles, the inter-particulate bonding force is suggested to be proportional to the Hamaker constant, the latter being proportional to the surface energy of the solid (6). Thus, in the case of a bond summation approach, a direct proportionality between tablet strength and surface energy is to be expected. Irrespective of the conception used to describe tablet strength (as described above), the energy of the particle surfaces involved in the inter-particulate bonding is a fundamental factor for the tensile strength of such solid bodies. Numerous papers discussing material factors control- ling the powder compactibility can be found in the literature, covering aspects such as the dimensions and the compression behaviour of the particles (1). However, few reports have specifically discussed the relationship between powder com- pactibility and particle surface energy (7–9). Sakr and Pilpel (10) compacted lactose particles coated with surfactants and they reported that an increasing concentration of surfactant decreased the tablet tensile strength, most profoundly at low concentrations. In a report by El Gindy and Samaha (11), a 0724-8741/08/1200-2750/0 # 2008 Springer Science + Business Media, LLC 2750 Pharmaceutical Research, Vol. 25, No. 12, December 2008 ( # 2008) DOI: 10.1007/s11095-008-9639-7 1 Department of Pharmacy, Uppsala University, Box 580, 751 23 Uppsala Sweden. 2 Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, Box 534, 75121 Uppsala, Sweden. 3 The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK. 4 To whom correspondence should be addressed. (e-mail: denny. mahlin@farmaci.uu.se)