Particle Engineering in Pharmaceutical Solids Processing: Surface Energy 
Considerations

During the past 10 years particle engineering in the pharmaceutical industry has become a topic of increasing importance. Engineers and pharmacists need to understand and control a range of key unit manufacturing operations such as milling, granulation, crystallisation, powder mixing and dry powder inhaled drugs which can be very challenging. It has now become very clear that in many of these particle processing operations, the surface energy of the starting, intermediate or final products is a key factor in understanding the processing operation and or the final product performance. This review will consider the surface energy and surface energy heterogeneity of crystalline solids, methods for the measurement of surface energy, effects of milling on powder surface energy, adhesion and cohesion on powder mixtures, crystal habits and surface energy, surface energy and powder granulation processes, performance of DPI systems and finally crystallisation conditions and surface energy. This review will conclude that the importance of surface energy as a significant factor in understanding the performance of many particulate pharmaceutical products and processes has now been clearly established. It is still nevertheless, work in progress both in terms of development of methods and establishing the limits for when surface energy is the key variable of relevance.

[1]  I. Larson,et al.  Characterization of the surface properties of a model pharmaceutical fine powder modified with a pharmaceutical lubricant to improve flow via a mechanical dry coating approach. , 2011, Journal of pharmaceutical sciences.

[2]  R. Davé,et al.  Investigating the applicability of inverse gas chromatography to binary powdered systems: an application of surface heterogeneity profiles to understanding preferential probe-surface interactions. , 2013, International journal of pharmaceutics.

[3]  D. Williams,et al.  The use of inverse phase gas chromatography to study the change of surface energy of amorphous lactose as a function of relative humidity and the processes of collapse and crystallisation. , 2001, International journal of pharmaceutics.

[4]  Jerry Y. Y. Heng,et al.  The Effects of Milling on the Surface Properties of Form I Paracetamol Crystals , 2006, Pharmaceutical Research.

[5]  C. Roberts,et al.  Characterization of Drug Particle Surface Energetics and Young’s Modulus by Atomic Force Microscopy and Inverse Gas Chromatography , 2005, Pharmaceutical Research.

[6]  J. Heng,et al.  Computing the Surface Energy Distributions of Heterogeneous Crystalline Powders , 2011 .

[7]  Arvind K. Bansal,et al.  Effect of Crystal Habit on Intrinsic Dissolution Behavior of Celecoxib Due to Differential Wettability , 2014 .

[8]  J. J. Bikerman,et al.  The Surface Roughness and Contact Angle. , 1950 .

[9]  A. Cassie,et al.  Wettability of porous surfaces , 1944 .

[10]  John N. Staniforth,et al.  The Cohesive-Adhesive Balances in Dry Powder Inhaler Formulations I: Direct Quantification by Atomic Force Microscopy , 2004, Pharmaceutical Research.

[11]  Mohamed A. Mostafa,et al.  Acid-Base Interactions in Polymer Adsorption , 1978 .

[12]  R. Rowe Polar/non-polar interactions in the granulation of organic substrates with polymer binding agents , 1989 .

[13]  C. Prestidge,et al.  Wettability studies of morphine sulfate powders. , 2000, International journal of pharmaceutics.

[14]  Martyn C. Davies,et al.  Characterization of Particle-Interactions by Atomic Force Microscopy: Effect of Contact Area , 2003, Pharmaceutical Research.

[15]  P. Mulvaney,et al.  Characterisation of adhesional properties of lactose carriers using atomic force microscopy. , 2001, Journal of pharmaceutical and biomedical analysis.

[16]  R. Rowe Correlation between predicted binder spreading coefficients and measured granule and tablet properties in the granulation of paracetamol , 1990 .

[17]  J. Watts,et al.  Determination of surface heterogeneity of D-mannitol by sessile drop contact angle and finite concentration inverse gas chromatography. , 2010, International journal of pharmaceutics.

[18]  P. York,et al.  Analysis of the surface energy of pharmaceutical powders by inverse gas chromatography. , 2002, Journal of pharmaceutical sciences.

[19]  John F. Gamble,et al.  Surface energy analysis as a tool to probe the surface energy characteristics of micronized materials--a comparison with inverse gas chromatography. , 2012, International journal of pharmaceutics.

[20]  E. Yonemochi,et al.  Changes in surface properties by granulation and physicochemical stability of granulated amorphous cefditoren pivoxil with additives. , 2004, International journal of pharmaceutics.

[21]  D. A. Wilson,et al.  Crystal Habits and the Variation in Surface Energy Heterogeneity , 2009 .

[22]  K. Wilson,et al.  Anisotropic surface energetics and wettability of macroscopic form I paracetamol crystals. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[23]  S. Hasegawa,et al.  Determination of the structural relaxation at the surface of amorphous solid dispersion using inverse gas chromatography. , 2009, Journal of pharmaceutical sciences.

[24]  A. Narang,et al.  Decoupling the contribution of dispersive and acid-base components of surface energy on the cohesion of pharmaceutical powders. , 2014, International journal of pharmaceutics.

[25]  P. Stewart,et al.  Characterising surface energy of pharmaceutical powders by inverse gas chromatography at finite dilution , 2012, The Journal of pharmacy and pharmacology.

[26]  D. H. Kaelble,et al.  Dispersion-Polar Surface Tension Properties of Organic Solids , 1970 .

[27]  C. Doherty,et al.  A comparison of two contact angle measurement methods and inverse gas chromatography to assess the surface energies of theophylline and caffeine , 1996 .

[28]  A. Narang,et al.  Effect of crystal habits on the surface energy and cohesion of crystalline powders. , 2014, International journal of pharmaceutics.

[29]  J. Heng,et al.  Role of Surface Chemistry and Energetics in High Shear Wet Granulation , 2011 .

[30]  Graham Buckton,et al.  Determination of the changes in surface energetics of cefditoren pivoxil as a consequence of processing induced disorder and equilibration to different relative humidities. , 2004, International journal of pharmaceutics.

[31]  Martyn C. Davies,et al.  An Atomic Force Microscopy Study of the Effect of Nanoscale Contact Geometry and Surface Chemistry on the Adhesion of Pharmaceutical Particles , 2004, Pharmaceutical Research.

[32]  E. Lesniewska,et al.  Affinity scale between a carrier and a drug in DPI studied by atomic force microscopy. , 2002, International journal of pharmaceutics.

[33]  R. Davé,et al.  Passivation of high-surface-energy sites of milled ibuprofen crystals via dry coating for reduced cohesion and improved flowability. , 2013, Journal of pharmaceutical sciences.

[34]  Mojtaba Ghadiri,et al.  Triboelectric charging of powders: A review , 2010 .

[35]  D. F. Steele,et al.  Surface Energy of Microcrystalline Cellulose Determined by Capillary Intrusion and Inverse Gas Chromatography , 2008, The AAPS Journal.

[36]  C. L. Young,et al.  Physicochemical measurement by gas chromatography , 1979 .

[37]  M. Murphy,et al.  The crystal engineering of salbutamol sulphate via simulated pulmonary surfactant monolayers. , 2013, International journal of pharmaceutics.

[38]  L. Lavielle,et al.  The Role of the Interface in Carbon Fibre-Epoxy Composites , 1987 .

[39]  F. Fowkes,et al.  Spectral shifts in acid-base chemistry. 1. van der Waals contributions to acceptor numbers , 1990 .

[40]  D. Gray,et al.  Adsorption of n-alkanes at zero surface coverage on cellulose paper and wood fibers , 1980 .

[41]  A. V. Kiselev,et al.  Gas-adsorption chromatography , 1969 .

[42]  P. York,et al.  Determination of the surface properties of two batches of salbutamol sulphate by inverse gas chromatography , 1994 .

[43]  C. V. Oss,et al.  Interfacial Forces in Aqueous Media , 1994 .

[44]  R. Nisman,et al.  Investigation of the surface free energy of pharmaceutical materials from contact angle, sedimentation, and adhesion measurements , 1993 .

[45]  Jerry Y Y Heng,et al.  Wettability of paracetamol polymorphic forms I and II. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[46]  S. Yariv,et al.  Physical Chemistry of Surfaces , 1979 .

[47]  A. Nokhodchi,et al.  Theophylline Cocrystals Prepared by Spray Drying: Physicochemical Properties and Aerosolization Performance , 2013, AAPS PharmSciTech.

[48]  M. Kaufman,et al.  Wettability of pharmaceutical solids: its measurement and influence on wet granulation , 2002 .

[49]  D. K. Owens,et al.  Estimation of the surface free energy of polymers , 1969 .

[50]  I. Larson,et al.  Use of surface energy distributions by inverse gas chromatography to understand mechanofusion processing and functionality of lactose coated with magnesium stearate. , 2011, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[51]  K. Waters,et al.  Inverse gas chromatography applications: a review. , 2014, Advances in colloid and interface science.

[52]  Glenn C. Vogel,et al.  Four-parameter equation for predicting enthalpies of adduct formation , 1971 .

[53]  P. York,et al.  Characterisation of the surface properties of α-lactose monohydrate with inverse gas chromatography, used to detect batch variation , 1996 .

[54]  Nikin Patel,et al.  Determination of the Surface Free Energy of Crystalline and Amorphous Lactose by Atomic Force Microscopy Adhesion Measurement , 2006, Pharmaceutical Research.

[55]  Daryl R. Williams,et al.  The Use of Inverse Phase Gas Chromatography to Measure the Surface Energy of Crystalline, Amorphous, and Recently Milled Lactose , 2001, Pharmaceutical Research.

[56]  E. Kauppinen,et al.  Investigations on particle surface characteristics vs. dispersion behaviour of L-leucine coated carrier-free inhalable powders. , 2010, International journal of pharmaceutics.

[57]  Dongsheng Bu,et al.  A control strategy for bioavailability enhancement by size reduction: Effect of micronization conditions on the bulk, surface and blending characteristics of an active pharmaceutical ingredient , 2014 .

[58]  G. Buckton,et al.  A study of the differences between two amorphous spray-dried samples of cefditoren pivoxil which exhibited different physical stabilities. , 2005, International journal of pharmaceutics.

[59]  Changquan Calvin Sun,et al.  Impact of Crystal Habit on Biopharmaceutical Performance of Celecoxib , 2013 .

[60]  P. Young,et al.  Surface Energy and Interparticle Force Correlation in Model pMDI Formulations , 2005, Pharmaceutical Research.

[61]  K. Wilson,et al.  Anisotropic surface chemistry of aspirin crystals. , 2007, Journal of pharmaceutical sciences.

[62]  Alexander Bismarck,et al.  Anisotropic surface chemistry of crystalline pharmaceutical solids , 2006, AAPS PharmSciTech.

[63]  L. Jia,et al.  Comparison of Dorris-Gray and Schultz methods for the calculation of surface dispersive free energy by inverse gas chromatography. , 2011, Journal of chromatography. A.

[64]  J. Heng,et al.  Inverse gas chromatographic method for measuring the dispersive surface energy distribution for particulates. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[65]  J. Raper,et al.  Characterisation and aerosolisation of mannitol particles produced via confined liquid impinging jets. , 2009, International journal of pharmaceutics.

[66]  K. Amighi,et al.  Lactose characteristics and the generation of the aerosol. , 2012, Advanced drug delivery reviews.

[67]  C. Volpe,et al.  Some Reflections on Acid-Base Solid Surface Free Energy Theories , 1997, Journal of colloid and interface science.

[68]  F. Fowkes ATTRACTIVE FORCES AT INTERFACES , 1964 .

[69]  R. Good,et al.  Contact angle, wetting, and adhesion: a critical review , 1992 .

[70]  C. Roberts What can we learn from atomic force microscopy adhesion measurements with single drug particles? , 2005, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[71]  M. Ticehurst,et al.  An exploration of inter-relationships between contact angle, inverse phase gas chromatography and triboelectric charging data. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[72]  H. Steckel,et al.  Physico-chemical characterisation of surface modified particles for inhalation. , 2013, International journal of pharmaceutics.

[73]  R. C. Rowe,et al.  Surface free energy and polarity effects in the granulation of a model system , 1989 .

[74]  S. Itai,et al.  Evaluation of Crystallization Behavior on the Surface of Nifedipine Solid Dispersion Powder Using Inverse Gas Chromatography , 2013, Pharmaceutical Research.

[75]  M. Chaudhury,et al.  Additive and nonadditive surface tension components and the interpretation of contact angles , 1988 .

[76]  I. Saracovan,et al.  Measurement of the surface energy of lubricated pharmaceutical powders by inverse gas chromatography. , 2006, International journal of pharmaceutics.

[77]  E. Yonemochi,et al.  Factors affecting the apparent solubility of ursodeoxycholic acid in the grinding process. , 2003, International journal of pharmaceutics.

[78]  P. York,et al.  Characterisation of the surface energetics of milled dl-propranolol hydrochloride using inverse gas chromatography and molecular modelling , 1998 .

[79]  S. Srčič,et al.  The role of the surface free energy in the selection of a suitable excipient in the course of a wet-granulation method , 2005 .

[80]  W. Zisman,et al.  Contact angle, wettability, and adhesion , 1964 .

[81]  Daniel J. Burnett,et al.  Effect of Milling on Particle Shape and Surface Energy Heterogeneity of Needle-Shaped Crystals , 2012, Pharmaceutical Research.

[82]  J. Heng,et al.  Determination of the Surface Energy Distributions of Different Processed Lactose , 2007, Drug development and industrial pharmacy.

[83]  Yan Zhang,et al.  Evaluation of Milling Method on the Surface Energetics of Molecular Crystals Using Inverse Gas Chromatography , 2012 .

[84]  C. Prestidge,et al.  Face specific surface properties of pharmaceutical crystals. , 2002, Journal of pharmaceutical sciences.