Göran Alderborn

Bonding Surface area and Bonding Mechanism-Two Important Factors fir the Understanding of Powder Comparability

AbstractTwo factors could be regarded as primary factors for the compactability of powders: the dominating bond mechanism and the surface area over which these bonds are active. Owing to considerable experimental difficulties, these factors have not been evaluated in any detail for pharmaceutical materials. Instead, more indirect, secondary factors are normally studied and used for correlations with tablet strength. Such secondary factors are particle size, shape and surface texture. Also the importance of volume reduction mechanisms, i.e. elastic deformation, plastic deformation and particle fragmentation have been studied in detail.For the investigation of dominating bond mechanisms and estimation of the magnitude of the surface area of the solids involved in interparticulate attraction in compacts several pharmaceutical excipients representing both plastically deforming materials (sodium chloride, Avicel® PH 101, Sta-Rx 1500®, and sodium bicarbonate) and fragmenting materials (lactose, sucrose, paracet...

Compression behaviour and compactability of microcrystalline cellulose pellets in relationship to their pore structure and mechanical properties

Abstract Two series of microcrystalline cellulose pellets were produced by extrusion-spheronization and the size fraction 710–1000 μm was prepared by sieving. The preparation procedure gave nearly spherical pellets with similar shape and surface characteristics but markedly different porosity and mechanical properties. The pellets compressed by permanent deformation rather than by fragmentation. The degree of pellet deformation increased with an increased original pellet porosity while the mechanical strength of the pellets was not a primary factor in the compression behaviour of the pellets. The compactability of the pellets related directly to the original pellet porosity. The results indicate thus that the pellet porosity determined the degree of their deformation during compression which in turn controlled the pore structure and the tensile strength of the compact formed. A high degree of pellet deformation gave a low intergranular separation distance in the compact and promoted the formation of intergranular bonds of a high bonding force.

Increased metastable solubility of milled griseofulvin, depending on the formation of a disordered surface structure

Abstract The effect of mechanical processing on the solubility of griseofulvin was studied. Milling of griseofulvin produced an increased metastable solubility. The milling operation did not change the materials bulk thermal properties identifiable by DSC, nor did it alter the surface area of the individual primary particle size, to fully explain the apparent increase in solubility. However, the thermodynamic evaluation of milled griseofulvin showed an increase in free energy and a reduction in the heat of solution. This suggests that the increase in solubility was due to disordering of the solid structure, estimated to be about 5.8% w/w of the total mass and limited only to an external assumed surface layer 40–50 nm in thickness. The initial solubility levels obtained were found to be directly related to the solid solute particle surface structure. The slow decrease from the initially high metastable solubility level to the stable, low equilibrium solubility seemed to be controlled by a surface reaction mechanism, probably a solid-state rearrangement process and not by a solute molecular diffusion in the bulk solution.

Studies on direct compression of tablets X. Measurement of tablet surface area by permeametry

Abstract A method for measuring the permeability of tablets was developed. The specific surface areas of the tablets were then deduced using the permeability equation corrected for slip flow. The method was tested on some experimental parameters which had only a minor effect on the tablet surface area. The effect of compaction pressure on tablet surface area, obtained using both a gas adsorption method and a permeametry technique, were then studied for sodium chloride and saccharose (fraction 212–250 μm). The two methods gave similar surface area-pressure curves up to 150 MPa, both substances showing increasing surface area with pressure but a faster increase for saccharose. The permeametry surface area curves continued to increase within the whole pressure range, while the gas adsorption surface area levelled out for saccharose and decreased at the highest pressures for sodium chloride.

Relationships between the effective interparticulate contact area and the tensile strength of tablets of amorphous and crystalline lactose of varying particle size

The aim of this study was to experimentally evaluate an equation for describing tablet tensile strength by studying relationships between the measured tensile strength and the calculated effective interparticulate contact area in tablets prepared from varying size fractions of amorphous and crystalline lactose at varying pressures. Amorphous lactose produced tablets of higher tensile strength than crystalline lactose and there was a tendency for reduced particle size to increase tablet strength. The tablet tensile strength correlated reasonably well with the effective area of contact for each material after compensation for a particle size-related intercept. It was thus concluded that the tensile strength equation under investigation reflects a structural property of the tablet which correlates with the tensile strength of the tablet. The slope of the tensile strength-contact area relationship differed between the materials and original particle size also had a small effect on this parameter. The results indicate thus also that the differences in compactability between amorphous and crystalline lactose are mainly the result of differences in bonding capacity, although differences in particle deformability also play a limited part.

The effect of moisture content on the compression and bond-formation properties of amorphous lactose particles

Abstract A lactose solution was spray-dried and the particles obtained were stored at relative humidities of 0, 11, 22 and 33%. The moisture content (gravimetric analysis), crystallinity (microcalorimetry), particle density (air pycnometry) and glass transition temperature (differential scanning calorimetry) of the particles were determined and compacts were prepared (50–200 MPa). From porosity-applied pressure profiles, the yield pressure for the materials was calculated and the tensile strength and porosity of the compacts were determined. Compacts were also examined in an electron microscope. The moisture content of the amorphous material varied between 0 and 6.2 wt% and an increased moisture content related rectilinearly to a reduced particle density, a reduced glass transition temperature and a reduced yield pressure. An increased moisture content gave an increased tablet tensile strength and a reduced tablet porosity. Different relationships between tablet strength and porosity were obtained dependent on the moisture content of the particles, while a single relationship seemed to exist between tablet strength and a contact area coefficient. To conclude, amorphous lactose powders reduced in volume due to particle deformation, and powder compression was facilitated by an increased moisture content due to an increased deformability of the particles in their glassy state. The particle deformability controlled the area of contact formed between the particles during compression, which controlled the tablet tensile strength. Particles seemed to bind by adsorption bonding and, at high compaction pressures, by solid bridges.

Degree of pellet deformation during compaction and its relationship to the tensile strength of tablets formed of microcrystalline cellulose pellets

The degree of deformation and densification of pellets during compression have been quantified. The relationship between the degree of deformation of the pellets and their compactability were also studied. Two sets of pellets of microcrystalline cellulose, showing a marked difference in intragranular porosity, were prepared by extrusion-spheronization. The pellets were mixed with a lubricant and compacted at a series of applied pressures. The individual pellets were retrieved after compression by tablet deaggregation and the porosity (densification behaviour) and dimensions (deformation behaviour) of the retrieved pellets were determined. Tensile strength of compacts prepared of unlubricated pellets was also determined. The incidence of pellet fragmentation was almost non-existent during the compression for both sets of pellets. The low porosity pellets showed only limited local permanent deformation during compression and the pellet porosity was unaffected by the compression. The high porosity pellets showed both a high compression-induced change in shape and a marked decrease in pellet porosity. Tensile strength values of tablets of unlubricated pellets indicated that a marked bulk structure deformation of the pellets was necessary for the formation of intergranular contacts of a high bonding force in the compact.

Studies on direct compression of tablets. XL Characterization of particle fragmentation during compaction by permeametry measurements of tablets

Abstract The usefulness of measuring tablet surface areas by a permeametry technique for the characterization of particle fragmentation during compaction was evaluated. Eight materials (sieve fraction 212–250 μm) with varying and documented consolidation behavior were compacted at a series of pressures in the range 20–200 MPa. The permeability of the tablets was measured and the specific surface area of the tablets was calculated. For all materials the tablet surface area increased with increased compaction pressure within the pressure range studied. However the slope of the curves differed between the materials and they could be rank ordered in agreement with earlier experiences of their fragmentation propensity. The permeametry procedure therefore seems acceptable for estimating particle fragmentation during compaction.

The effect of particle fragmentation and deformation on the interparticulate bond formation process during powder compaction.

AbstractPurpose. The compression behaviour and the compactability of particles have been studied. In addition, an expression describing the bond strength over a tablet cross section was derived and these calculated values were compared with the experimentally determined tablet tensile strength values. Methods. The compression behaviour of particles of a series of size fractions of four materials were assessed by tablet surface areas (particle fragmentation propensity) and by yield pressures (particle deformability), derived from in die Heckel profiles. The porosity and the tensile strength of the tablets were also determined. Results. Sodium chloride and sodium bicarbonate possessed limited fragmentation while the converse applied for sucrose and lactose. Sodium chloride and sodium bicarbonate were the extreme materials with respect to particle deformability and compactability. Except for sodium chloride, a limited effect of original particle size on the compactability of the particles was observed. Conclusions. The observations on the compactability of the powders was explained by postulating that fragmentation affects mainly the number of bonds in a compact cross section, while deformation affects mainly the bonding force of these bonds, through a relationship with the contact area between a pair of particles. The deviations between the predicted strength of particle-particle bonds and the determined tensile strength values was explained by a high bonding capacity of some particles, e.g. due to an unpredicted high surface deformability, or by a fracture mechanic effect during tablet strength determination.

The effect of shape and porosity on the compression behaviour and tablet forming ability of granular materials formed from microcrystalline cellulose

The compression behaviour of two types of granules prepared from microcrystalline cellulose was evaluated. Three sets (low, intermediate and high intragranular porosity) of irregular granules and three sets of nearly spherical granules (called pellets) were prepared from microcrystalline cellulose by wet agglomeration or wet agglomeration followed by extrusion/spheronisation. The granules and pellets were similar in size. The range of intragranular porosity, although wide, was also similar for both types. The compression behaviour was evaluated in terms of the degree of compression, the appearance of the tablets and the size distribution of retrieved aggregates (after deaggregation). The compactability of the granules and pellets was also studied. Both types of granules kept their integrity during compression. The dominant mechanism during compression appeared to be permanent deformation. However, during compression of high porosity granules, fragmentation or attrition seemed to occur alongside deformation. Tablets formed from granules had a closer pore structure than those formed from pellets of equal intragranular porosity and the granules seemed to deform to a higher degree during compression. The total tablet porosity was almost independent of the intragranular porosity and the shape of the granules before compression. It is suggested that the degree of granule deformation was controlled by the intragranular porosity and voidage of each bed of granules before compression. The tensile strength of the tablets was also dependent on the porosity and the shape of the granules; tablets formed from irregular granules were stronger than those formed from pellets of an equal intragranular porosity.