Jonas Berggren

Effect of drying rate on porosity and tabletting behaviour of cellulose pellets

The purpose of this study was to investigate the effect of drying rate during static drying on certain physical properties of pellets. Pellets were prepared from microcrystalline cellulose by granulation with different agglomeration liquids (various ethanol/water ratios) and thereafter dried without agitation at different drying rates. The dry pellets were characterised with respect to their shape, porosity, and compression shear strength and the tensile strength of tablets formed from pellets with low and high drying rates was determined. Drying of the pellets occurred at a falling rate and the reduction in liquid content with time obeyed a first order type of relationship. An increased drying rate did not affect the shape and surface texture of the dried pellets and did not cause them to fracture. However, the drying conditions did affect pellet porosity, with an increased drying rate resulting in more porous pellets. Through a relationship with pellet porosity, the drying rate also affected the deformability of the pellets (as assessed from Kawakita 1/b values) and their ability to form tablets. Owing to a strong effect of porosity on pellet compactability, marked changes in tablet tensile strength with variations in drying rate may be obtained.

Drying behaviour of two sets of microcrystalline cellulose pellets

The objective was to study contraction and densification of two sets of microcrystalline cellulose pellets, prepared using water (W) or a 25/75% w/w water/ethanol (W/E) mixture, during drying. The pellets were dried on microscope slides, photographed and weighed at set times. The porosity of the dry pellets was determined by mercury pycnometry. From pellet size, weight and porosity data, contraction and densification of the pellets and the relationship of these to the liquid content of the pellets during drying were calculated. Both types of pellets contracted and densified during drying. The initial porosity was similar for both types, but the final porosity of the dry pellets was higher for the W/E pellets. Thus, the difference in final pellet porosity between the two types was caused by a difference in densification during drying rather than a different degree of densification during the pelletisation procedure. The contraction rate and the relationships between contraction and the volume of removed liquid, and contraction and the degree of liquid saturation differed between the two types of pellet. The difference in drying behaviour between the two types of pellets can be explained by a liquid related change in both contraction driving force and contraction counteracting force or by a different contraction mechanism.

Effect of Polymer Content and Molecular Weight on the Morphology and Heat- and Moisture-Induced Transformations of Spray-Dried Composite Particles of Amorphous Lactose and Poly(vinylpyrrolidone)

AbstractPurpose. The aim was to investigate the influence of polymer content and molecular weight on the morphology and heat- and moisture-induced transformations, as indicators of stability, of spray-dried composite particles of amorphous lactose and poly(vinylpyrrolidone) (PVP). Methods. Amorphous lactose and composite particles of amorphous lactose with different contents and molecular weights of PVP were prepared by spray drying. The nanostructure of the particles was analyzed by x-ray powder diffractometry, the morphology by light microscopy and SEM, the glass transition temperatures (Tg), crystallization temperatures (Tc), heats of crystallization and melting temperatures by differential scanning calorimetry, and moisture-induced crystallizations gravimetrically and by microcalorimetry. Results. All the types of particles prepared were amorphous. The Tg was unchanged or only marginally increased as a result of the inclusion of PVP. However, crystallization temperature, time to moisture-induced crystallization, and particle morphology were affected by both content and molecular weight of PVP. Conclusions. Increased content and molecular weight of PVP may have the potential to increase the physical stability of amorphous lactose. However, Tg seems not to be a relevant indicator for the stability of this type of amorphous composite materials.

Considerations on the quantitative analysis of apparent amorphicity of milled lactose by Raman spectroscopy.

The main purpose of the study was to evaluate various pre-processing and quantification approaches of Raman spectrum to quantify low level of amorphous content in milled lactose powder. To improve the quantification analysis, several spectral pre-processing methods were used to adjust background effects. The effects of spectral noise on the variation of determined amorphous content were also investigated theoretically by propagation of error analysis and were compared to the experimentally obtained values. Additionally, the applicability of calibration method with crystalline or amorphous domains in the estimation of amorphous content in milled lactose powder was discussed. Two straight baseline pre-processing methods gave the best and almost equal performance. By the succeeding quantification methods, PCA performed best, although the classical least square analysis (CLS) gave comparable results, while peak parameter analysis displayed to be inferior. The standard deviations of experimental determined percentage amorphous content were 0.94% and 0.25% for pure crystalline and pure amorphous samples respectively, which was very close to the standard deviation values from propagated spectral noise. The reasonable conformity between the milled samples spectra and synthesized spectra indicated representativeness of physical mixtures with crystalline or amorphous domains in the estimation of apparent amorphous content in milled lactose.

Comminution-amorphisation relationships during ball milling of lactose at different milling conditions

The purpose of the study was to investigate the relationship between comminution and amorphisation of α-lactose monohydrate particles during ball milling under different milling conditions, including ball-to-powder mass ratio, milling time and ball diameter. The results revealed that at a constant ball filling ratio, ball-to-powder mass ratio of 25:1 resulted in the lowest minimum particle diameter of ∼5μm and the highest degree of apparent amorphous content of 82%. The rate of comminution was high during early stage of milling whereas the degree of apparent amorphous content increased gradually at a slow rate. An increased ball-to-powder mass ratio during milling increased both the rate of comminution and the rate of amorphisation. Using a given ball-to-powder mass ratio, the ball diameter affected the degree of apparent amorphous content of the particles while the particle diameter remained unchanged. The relationship between comminution and amorphisation could be described as consisting of two stages, i.e. comminution dominated and amorphisation dominated stage. It was proposed that the rate constant of comminution and amorphisation are controlled by stress energy distribution in the milling jar and the stress energy distribution is regulated by the ball motion pattern that can be affected by the process parameter used.

Mechanism of Amorphisation of Micro-Particles of Griseofulvin During Powder Flow in a Mixer

The purpose of the research was to investigate the degree of solid-state amorphisation during powder flow and to propose a mechanism for this transformation. Micro-particles of griseofulvin (about 2 μm in diameter) were mixed in a shear mixer under different conditions to influence the inter-particulate collisions during flow, and the degree of amorphisation was determined by micro-calorimeter. The amorphisation of griseofulvin particles (GPs) during repeated compaction was also determined. The GPs generally became disordered during mixing in a range from about 6% to about 86%. The degree of amorphisation increased with increased mixing time and increased batch size of the mixer, whereas the addition of a lubricant to the blend reduced the degree of amorphisation. Repeated compaction using the press with ejection mode gave limited amorphisation, whereas repeated compaction without an ejection process gave minute amorphisation. It is concluded that during powder flow, the most important inter-particulate contact process that cause the transformation of a crystalline solid into an amorphous state is sliding. On the molecular scale, this amorphisation is proposed to be caused by vitrification, that is the melting of a solid because of the generation of heat during sliding followed by solidification into an amorphous phase.

Effect of milling on the plastic and the elastic stiffness of lactose particles

Abstract The purpose of this study was to investigate the effect of degree of disorder of a series of &agr;‐lactose monohydrate powders, prepared by milling for different time periods, on the plastic and the elastic stiffness of the particles. As references, a series of physical mixtures consisting of original crystalline particles and amorphous particles obtained by spray‐drying was used. In addition, the effect of powder pre‐storage humidity on the mechanical properties was investigated. For milled particles of a low degree of disorder, a decreased particle size increased the particle plastic stiffness. For milled particles of constant particle size, the plastic stiffness decreased with an increased degree of disorder while the elastic stiffness seemed nearly independent of the degree of disorder. The presence of moisture caused a recrystallisation of milled particles with low degree of disorder which increased their plastic stiffness. For the physical mixtures of crystalline and amorphous particles, similar relationships between plastic stiffness and amorphous content as for the milled powders were obtained. A reasonable explanation is that the nature of the milled particles is represented by a two‐state system with crystalline and amorphous domains. Graphical abstract Figure. No caption available.