The effect of ambient humidity and adsorbed water can be of critical importance in the processing of fine powders in air. Adsorbed water layers can influence the adhesive properties of the powder and may lead to difficulties in processing and handling. It has been shown, in the current work, that in ambient conditions the interaction between two solid surfaces is dominated by the force arising from the presence of adsorbed water layers. In the current work an atomic force microscopy technique has been developed to determine the separation distance at which two solid surfaces, i.e. the AFM cantilever tip and the sample surface, 'jump' into contact. From the separation distance the thickness of the adsorbed water layers on the cantilever tip and sample surface can be determined based on an analytical method originally developed by Forcada (1993), which considers the interacting forces which cause the 'jump' to contact. The adsorbed layer thickness, as a function of relative humidity, has been determined for silicon wafer, using the AFM technique. This localized adsorption isotherm has been compared with those published by other investigators, who have used different measurement techniques on large sample areas. The adsorption isotherm determined using the AFM technique reports adsorbed layer thicknesses that are significantly larger than those measured by other investigators. Adsorption isotherms have been determined, using the AFM technique, for three forms of a-lactose monohydrate, which is widely used throughout the pharmaceutical industry. It was observed that each form of lactose gave a different level of water adsorption. Laboratory grown crystals exhibited the greatest levels of moisture adsorption, while commercially produced milled a-lactose displayed lower levels of water adsorption. Differences in surface roughness may possibly explain the variation. For rough samples the probe tip makes contact with surface asperities and therefore does not detect the presence of condensed water in the surface valleys. It is also possible that surface contamination and process history may have influenced the levels of water adsorption but these are complex effects to quantify. Water adsorption isotherms were measured on bulk samples of classified lactose, to attempt to validate the AFM technique, developed in the current study. It can be observed that the adsorbed layer thicknesses determined using AFM are significantly larger than those inferred from bulk measurements. The AEM method provides layer thickness values which are approximately four times larger than what are believed to be the true values. This is seen for tests on silicon, aluminium and lactose surfaces. This discrepancy is thought to arise from the presence of the probe tip on the surface causing a local spatial inhomogeneity. The associated increase in surface potential will promote nucleation of water molecules, leading ultimately to capillary condensation.

Approximately 80% of pharmaceutical products and the ingredients required for their manufacture are in powder form. The solid dosage form (tablets and capsules) is manufactured by either dry-blending of fine powder ingredients or combining the ingredients in a wet granulation step, followed by drying. Arching, ratholing, caking, segregation and flooding are some of the commonly encountered flow problems in the handling of fine powders. These problems lead to losses worth thousands of dollars at production scale. Poor powder flowability is a consequence of the combined effects of many variables, including improper equipment design, particle size, size distribution, shape, moisture content and surface texture. In the present work, a systematic study has been performed to determine the relationship between the flowability of fine powders and their physical properties of mean size and size distribution, density and shape.<p> Flowability studies were done on six different powders: the NutraSweet® Brand sweetener (aspartame), Respitose ML001, Alpha-D-Lactose monohydrate, the pharmaceutical binder Methocel (R) F50 Premium Hydroxypropyl methylcellulose- HPMC, a placebo pharmaceutical granulate, and common pastry flour. Scanning electron microscopy (SEM) and stereomicroscopy were used for particle shape and size analysis. Particle size distribution was determined using the laser light scattering technique. Powder flowability was measured using shear strength, angle of repose, and tapped-to-bulk density measurements. A novel method of measuring the dynamic angle of repose using electrical capacitance tomography (ECT) was developed. <p> Analysis of the images from microscopy revealed that the particles of aspartame and HPMC powders were elongated, the particles of ML001, pastry flour and lactose monohydrate powders were irregular, and the particles of placebo granulate were nearly spherical. Particle size was found to be the most reliable indicator of powder flowability, with decreasing particle size corresponding to lower flowability; however other parameters such as particle elongation and irregularity, were also found to have an influence on powder flowability. Although HPMC and pastry flour had similar particle sizes, they exhibited differences in flowability. This can be explained by the greater irregularity of the flour particles. Particle irregularity may cause mechanical interlocking between the particles, thus reducing powder flowability. ECT was found to be a promising non-intrusive tool for the measurement of the dynamic angle of repose. Unlike other methods for the measurement of dynamic angle of repose, the results obtained from ECT were not influenced by the effect of end caps. The present technique could be used by pharmaceutical industries in process analytical technology (PAT) for the detection and elimination of potential flow problems early in the manufacturing process.

Approximately 80% of pharmaceutical products and the ingredients required for their manufacture are in powder form. The solid dosage form (tablets and capsules) is manufactured by either dry-blending of fine powder ingredients or combining the ingredients in a wet granulation step, followed by drying. Arching, ratholing, caking, segregation and flooding are some of the commonly encountered flow problems in the handling of fine powders. These problems lead to losses worth thousands of dollars at production scale. Poor powder flowability is a consequence of the combined effects of many variables, including improper equipment design, particle size, size distribution, shape, moisture content and surface texture. In the present work, a systematic study has been performed to determine the relationship between the flowability of fine powders and their physical properties of mean size and size distribution, density and shape.<p> Flowability studies were done on six different powders: the NutraSweet® Brand sweetener (aspartame), Respitose ML001, Alpha-D-Lactose monohydrate, the pharmaceutical binder Methocel (R) F50 Premium Hydroxypropyl methylcellulose- HPMC, a placebo pharmaceutical granulate, and common pastry flour. Scanning electron microscopy (SEM) and stereomicroscopy were used for particle shape and size analysis. Particle size distribution was determined using the laser light scattering technique. Powder flowability was measured using shear strength, angle of repose, and tapped-to-bulk density measurements. A novel method of measuring the dynamic angle of repose using electrical capacitance tomography (ECT) was developed. <p> Analysis of the images from microscopy revealed that the particles of aspartame and HPMC powders were elongated, the particles of ML001, pastry flour and lactose monohydrate powders were irregular, and the particles of placebo granulate were nearly spherical. Particle size was found to be the most reliable indicator of powder flowability, with decreasing particle size corresponding to lower flowability; however other parameters such as particle elongation and irregularity, were also found to have an influence on powder flowability. Although HPMC and pastry flour had similar particle sizes, they exhibited differences in flowability. This can be explained by the greater irregularity of the flour particles. Particle irregularity may cause mechanical interlocking between the particles, thus reducing powder flowability. ECT was found to be a promising non-intrusive tool for the measurement of the dynamic angle of repose. Unlike other methods for the measurement of dynamic angle of repose, the results obtained from ECT were not influenced by the effect of end caps. The present technique could be used by pharmaceutical industries in process analytical technology (PAT) for the detection and elimination of potential flow problems early in the manufacturing process.