M. B. James

The influence of constant and changing relative humidity of the air on the autoadhesion force between pharmaceutical powder particles

The influence of the press-on force applied and the relative humidity of the air during the storage of autoadhesion samples made from lactose monohydrate or salmeterol xinafoate has been studied using the centrifuge technique. Capillary forces can be obtained for lactose monohydrate if subjected to a relative humidity of 75% or more. The resulting strong autoadhesion forces are reversible by subsequently storing the autoadhesion samples at a low humidity environment. The strength of the capillary forces depends on the storage time, and to reach an equilibrium level requires more than 72 h. For the less polar salmeterol xinafoate the performance of capillary forces could not be proved with certainty. It appears that a very small increase in autoadhesion force at higher relative humidity levels is more likely caused by adsorbed water acting as a plasticizer. Model calculations of capillary forces did not prove successful in predicting the autoadhesion force of the materials if stored at a high relative humidity of the air. The knowledge of the surface free energy and its polar component gave a better basis for a prediction.

Assessment of adhesion and autoadhesion forces between particles and surfaces

A centrifuge technique has been used to investigate the autoadhesion force between particles and a plane surface of the same material compacted into a disk, which is resistant to the centrifugal force. When measured by profilemetry, these compact surfaces are rougher than metal or plastic surfaces used in previous studies. This results in a change of the detachment force distribution from a log-normal to a right-shifted distribution. The relationship between press-on force and median autoadhesion force depends on particle size, shape and particle surface morphology of the powder particles autoadhered. The lower the autoadhesion force, the greater the possibility that the substance can be used in a single-component powder application. The bulk properties of the powders such as cohesiveness or free powder flow were found to be related to the autoadhesion force. Estimation of the distance between the particles and surfaces has been made based on the Lifshitz-van der Waals constant derived from low frequency ...

The adhesion force of micronized Salmeterol Xinafoate particles to pharmaceutically relevant surface materials

The adhesion of micronized Salmeterol Xinafoate to various surface materials has been investigated by the centrifuge technique. The adhesion of the drug to these materials used for manufacture and storage of interactive mixtures of the drug and milled lactose monohydrate depends on different properties of the surfaces. A longer contact with polyvinylchloride, polyethylene or aluminium surfaces, or a contact with these surfaces under mechanical pressure should be avoided because the adhesion force between the drug and these surfaces is much higher than between the drug and excipient particles. Hence detachment and a consequent loss of drug in the formulation could occur. Such a problem does not appear to exist for the contact with polyhydroxymethylene surfaces. Characteristics of the surface materials such as the surface free energy (acid - base concept), surface roughness and Youngs modulus were determined and related to the experimental results. The work of adhesion appeared to have a very important influence on the adhesion forces measured. About 20% of the work of adhesion was due to acid - base interactions. The larger the work of adhesion, the stronger was the adhesion between the particles and the surfaces in contact. Surface roughness reduced the adhesion force, and stiffer materials (having a high Youngs modulus) were found to have a lower adhesion force to the drug particles.

Assessment of adhesion and autoadhesion forces between particles and surfaces. Part II. The investigation of adhesion phenomena of Salmeterol Xinafoate and lactose monohydrate particles in particle-on-particle and particle-on-surface contact

The centrifuge technique has been used to compare particle-on-particle and particle-on-surface adhesion with Salmeterol Xinafoate particles on single lactose particles or compacted lactose surfaces. The results from particle-on-particle and particle-on-surface adhesion measurements are not equivalent in terms of median adhesion force. The assessment of adhesion using either particle-on-particle or particle-on-surface systems depends on the process on which information is required: e.g. mixing problems are better investigated by applying the particle-on-particle technique, whereas surface transport problems such as powder compaction or flow can be more appropriately studied using particle-on-surface measurements. Taking autoadhesion measurements from the previous study into account, adhesion and autoadhesion forces were found to allow the prediction and choice of mixture components for powder blends. The results suggest that the homogeneity of such a powder blend depends both on thermodynamic properties an...

Adhesion and friction between powders and polymer or aluminium surfaces determined by a centrifuge technique

Abstract Adhesion and friction phenomena between single particles of calcium carbonate and pre-gelatinized starch and solid surfaces made from polyoxymethylene polymer or aluminium were investigated using a centrifuge technique. In the case of pure adhesion between the contiguous bodies, the experiments indicate that surface roughness, hydrophilic/energetic surface properties and plastic/elastic properties are involved, but the dominant factor varies from system to system. The results indicate that frictional force depends primarily on the particle properties rather than on the substrate surface properties. The softer pregelatinized starch appears to have greater surface contact showing higher friction properties than the harder calcium carbonate. A direct determination of the frictional force for both powdered materials was not possible, but the force necessary to push the particles along the substrate surface could be estimated.

The influence of physical properties of the materials in contact on the adhesion strength of particles of salmeterol base and salmeterol salts to various substrate materials

The adhesion force between salmeterol base and a series of chemically related salmeterol salts to various macroscopically flat substrate materials has been investigated. The substrates varied in their surface roughness, surface free energy, and Youngs modulus. The results suggest that the adhesion force of a particulate material to a macroscopically flat substrate depends on the physical properties of the substrate such as surface roughness, surface free energy and Youngs modulus, but there is no universal relationship. The properties of both the particles and the substrates have to be considered for possible interactions. A knowledge of the Hansen-solubility parameters of the particulate materials allows a prediction of rank order of the adhesion strength of particulate materials to a given substrate, but requires a knowledge of similar parameters for the substrate material also. The general rule is that materials which have, for example, similar hydrogen bonding terms or similar dispersion terms adher...

The determination of the coefficient of dynamic friction of organic powder compacts on steel

Abstract A practical experimental model system has been successfully used to study the frictional response of organic powder compacts sliding across a polished steel plate, representative of the die bore of a production compaction system. This system offers a controlled approach to the study of frictional phenomena occurring during compaction and facilitates a more detailed investigation into the fundamental mechanisms of friction than a simple resolution of forces within a punch and die apparatus. For acetylsalicyclic acid sliding on steel, the dynamic friction coefficient was found to be dependent on the displacement and, to a lesser extent, the initial normal load, whereas for PTFE on steel, the dynamic friction coefficient was independent of displacement and load and estimated at 0.09. Thus, soft organic materials exhibit very different frictional characteristics to those of brittle materials. These differences reflect the differing importance and magnitude of the three frictional components, adhesion, shear and ploughing.

The assessment of particle friction of a drug substance and a drug carrier substance

The centrifuge technique, which has been previously used in adhesion experiments, has been modified for use in single particle friction studies. Both flat compacted surfaces and large single particles were used as substrate surfaces to allow assessment of drug-drug, drug-drug carrier and drug carrier-drug carrier friction forces. Particle size, particle shape and surface roughness were identified as main factors influencing the change from a static into a dynamic friction process and the division between friction due to adhesion and ploughing. The forces of adhesion and friction were found to be proportional to the reversible energy of adhesion. The ratio between the force of adhesion and the press-on force applied and the ratio between the force of friction and the press-on force can be related to the yield stress and the reduced Youngs modulus of the materials in contact.

The influence of chemical structure on the friction properties between particles and compacted powder surfaces

Friction measurements on particles adhered to compacted powder surfaces have been undertaken by the centrifuge technique to investigate the influence of the variations in the chemical structure of a series of salts of salmeterol. Two mathematical models have been used to evaluate the experiments, and the coefficient of static friction, the friction force and the theoretical shear force on compacted powder surfaces of lactose monohydrate and salmeterol xinafoate have been derived. The results show differences in the mechanism of friction and also divide the five compounds into comparatively hard (salmeterol base and sulfate) and soft (salmeterol 4-chlorobenzoate, salicylate and xinafoate) materials. The hydrophilic nature of the particulate material was found to be indicative of its friction properties on a hydrophobic surface, and vice versa. The ability of a material to adsorb water is reflected in the relative hydrogen bonding coefficient (Hansen-solubility parameter), and a linear relationship was found between this coefficient and the friction force obtained. Water can act as a lubricant reducing the friction between two surfaces. The friction between like materials in contact was found to be minimal. The results also imply that no general descriptor of the chemical structure of related compounds, which would allow the prediction of friction properties, exists. Instead, the descriptor needs to be chosen according to the properties of the surfaces in contact, or friction experiments have to be performed.

The adhesion strength of particles of salmeterol base and a series of salmeterol salts to compacted lactose monohydrate surfaces

The effect of a systematic change in the chemical structure of salmeterol base, using different salts, on the adhesion force to compacted lactose monohydrate surfaces, a possible carrier excipient in dry powder aerosols, has been investigated. The chemical structures and the resulting polarity of the materials have been described using the Hansen-solubility parameter approach. From the results it is concluded that a prediction of the ranking of the adhesion strength of a series of chemically related compounds to a defined surface is only partially possible from a knowledge of the primary chemical structures using the Hansen-solubility parameter approach. Differences in the molecular configuration and differences in the surface roughness of the powder particles adhered are also important considerations. These factors may dominate over the influence of the primary chemical structure. The appropriate deformation characteristics such as ductility or brittleness cannot be predicted from the chemical structure ...