Biomedical subjects

Göran Alderborn

Publications and source records attributed to Göran Alderborn.

17 recordsLinked to original sources

PubMed2006

Effect of preparation method on compactability of paracetamol granules and agglomerates.

The objective of this study was to investigate the effect of fracture strength of paracetamol particles on their compactability. For this purpose two series of paracetamol particles were prepared by crystal agglomeration and by granulation using different solvents. A free flowing particle size fraction of all types of particles was characterized with respect to their shape, degree of agglomeration and single fracture strength. The powders were compressed to tablets and the compression mechanism of the particles and the evolution in tablet micro-structure were assessed by compression parameters derived from the Heckel and Kawakita equations and by a tablet permeabililty coefficient. Tablet tensile strength and porosity were determined. The degree of deformation and fragmentation during compression varied between agglomerates and granules and was dependent on their failure strength. The granules varied in compactability with particle failure strength while the agglomerates showed limited variation. It is proposed that, the dominant mechanism of compression for the granules was permanent deformation while for the agglomerates it was fragmentation. It was thus found that the compression mechanism of the particles was dependent on both the degree of agglomeration and the particle failure strength.

Acetaminophen↗

PubMed2006

Conductivity percolation in loosely compacted microcrystalline cellulose: An in situ study by dielectric spectroscopy during densification.

The present study aims at contributing to a complete understanding of the water-induced ionic charge transport in cellulose. The behavior of this transport in loosely compacted microcrystalline cellulose (MCC) powder was investigated as a function of density utilizing a new type of measurement setup, allowing for dielectric spectroscopy measurement in situ during compaction. The ionic conductivity in MCC was found to increase with increasing density until a leveling-out was observed for densities above approximately 0.7 g/cm3. Further, it was shown that the ionic conductivity vs density followed a percolation type behavior signifying the percolation of conductive paths in a 3D conducting network. The density percolation threshold was found to be between approximately 0.2 and 0.4 g/cm3, depending strongly on the cellulose moisture content. The observed percolation behavior was attributed to the forming of interparticulate bonds in the MCC and the percolation threshold dependence on moisture was linked to the moisture dependence of particle rearrangement and plastic deformation in MCC during compaction. The obtained results add to the understanding of the density-dependent water-induced ionic transport in cellulose showing that, at given moisture content, the two major parameters determining the magnitude of the conductivity are the connectedness of the interparticluate bonds and the connectedness of pores with a diameter in the 5-20 nm size range. At densities between approximately 0.7 and 1.2 g/cm3 both the bond and the pore networks have percolated, facilitating charge transport through the MCC compact.

Cellulose↗

PubMed2006

The influence of PVP incorporation on moisture-induced surface crystallization of amorphous spray-dried lactose particles.

We have recently shown that atomic force microscopy (AFM) may be an appropriate method for characterisation of the re-crystallization of amorphous particles. In this study, spray-dried composite particles consisting of lactose and polyvinyl pyrrolidon (PVP) were characterised by AFM and electron spectroscopy for chemical analysis (ESCA), and their response on increasing the relative humidity (RH) was investigated. The PVP content in the particles used was 0, 5 or 25 wt.% of either PVP K17 or PVP K90. All composite particles were found to be enriched with PVP at the surface. The incorporation of PVP in the particles influenced the way the particles responded to an increase in RH. The specific RH interval in which the surface of the particles smoothened and the RH where crystallization could be detected, increased with an increase in the amount and molecular weight of the PVP in the particles. The crystallization kinetics of single particles was analysed with AFM and by utilising the JMAK equation. The rate constant for this transformation increased in an exponential manner with increasing RH. Furthermore, above the RH needed for the crystallization to occur, the exponential increase in the crystallization rate was larger for particles with higher polymer content which indicates that the stabilising effect decreases as the water content in the particles becomes higher. In this study we report a method for determination of crystallization kinetics on single composite particles, which is valuable when evaluating the effect of stabilisers in amorphous powders.

Crystallization↗

PubMed2005

Particle size distribution and evolution in tablet structure during and after compaction.

The objective of this study was to investigate the effect of the distribution in size of free-flowing particles for the evolution in tablet structure and tablet strength. For sucrose and sodium chloride, three powders of different size distributions were prepared by mixing predetermined quantities of particle size fractions. For paracetamol, three batches with varying particle size distributions were prepared by crystallisation. The powders were formed into tablets. Tablet porosity and tensile strength were determined directly after compaction and after short-term storage at two different relative humidities. Tablets were also formed after admixture of a lubricant (magnesium stearate) and the tablet tensile strength was determined. For the test materials used in this study, the spread in particle size had no influence on the evolution in tablet porosity and tensile strength during compression. However, the spread in particle size had a significant and complex influence on the short-term post-compaction increase in tablet tensile strength. The effect of the spread was related to the instability mechanism and the presence of lubricant. It is concluded that the distribution in size of free-flowing particles is not critical for the tablet porosity but may give significant effects on tablet tensile strength due to a post-compaction reaction.

Acetaminophen↗

PubMed2005

Evolution of distributions and spatial correlations of single-particle forces and stresses during compression of ductile granular materials.

Uniaxial compression of disordered packings of millimeter-sized ductile particles formed from microcrystalline cellulose is investigated experimentally, at compression pressures in the vicinity of the minimum pressure required to form a coherent compact. Distributions of normal forces and stresses exerted by individual particles on a confining wall are determined. Spatial force and stress correlations are investigated. The distribution of normal forces is found to narrow with increasing pressure, but no indication of a crossover to a Gaussian decay at high forces is observed. The distribution of normal stresses is found to be considerably more Gaussian in shape for all pressures investigated. This finding may be interpreted as resulting from a positive correlation between the area corresponding to each particle and the force it experienced during compression. Spatial force and stress correlations are observed for distances smaller than three particle diameters. The spatial stress correlations indicate that the mode of stress transmission changes when the compression pressure exceeds the minimum pressure required to form a coherent compact.

Journal Article↗

PubMed2004

Moisture-induced surface crystallization of spray-dried amorphous lactose particles studied by atomic force microscopy.

The aim of this study was to show that atomic force microscopy (AFM) can be used to obtain mechanistic and kinetic information about the process of moisture-induced surface crystallization of single particles of amorphous lactose. Completely amorphous lactose particles were prepared by spray-drying a solution of alpha-lactose monohydrate, and moisture-induced crystallization was monitored for a bed of particles by microcalorimetry and for single particles by AFM. From the AFM images it was found that crystallization of the surface of single particles can be described in terms of a sequence of three events: an initial smoothening of the surface, formation of crystalline nanostructures dispersed in amorphous material, and growth of these structures to a complete crystalline surface. The surface roughness parameter rugosity was used to estimate the fraction crystalline surface, and the growth kinetics were found to obey the JMAK equation. The fraction crystalline surface at different times could also be estimated by determining the growth rate of individual crystals. It was concluded that AFM offers a unique means of visualizing the process of moisture-induced surface crystallization of amorphous particles and enables mechanistic and kinetic information about the process to be extracted.

Calorimetry↗

PubMed2004

Long-term stabilisation potential of poly(vinylpyrrolidone) for amorphous lactose in spray-dried composites.

The aim of this study was to investigate the potential of poly(vinylpyrrolidone) (PVP) to inhibit the crystallisation of amorphous lactose during storage of the composites up to 6 months. Short-term stability was assessed by microcalorimetry over 10 days and long-term stability by storage in desiccators with different relative humidities for 3 and 6 months. The solid-state structure of the particles after storage was analysed by differential scanning calorimetry. It was found that the presence of PVP increased the critical relative humidity (RH) for crystallisation relative to the pure lactose and both the proportion and the molecular weight of the PVP affected the stabilisation of the amorphous phase. The difference in critical RH between the materials increased over time. The T(g) of the materials was generally reduced due to the absorption of water and it is suggested that the inhibiting effect therefore is related mainly to a specific interaction between lactose and PVP, rather than to a counteracting effect of the polymer on the moisture induced depression of T(g).

Calorimetry, Differential Scanning↗

PubMed2004

Compression behaviour and tablet-forming ability of spray-dried amorphous composite particles.

The aim of this study was to investigate the compression behaviour and tablet-forming ability of spray-dried amorphous two- and three-component composite particles. Particles of lactose alone, two-component particles of lactose and PVP, and three-component particles of lactose, PVP and a small amount of polysorbate 80 were prepared by spray-drying. Two qualities of PVP with different molecular weights were used for the preparation of both types of particles. The particles were characterised with respect to permeametry surface area, moisture content, particle and bulk density, glass transition and crystallisation temperature, and heat of crystallisation. The tablet tensile strength of the different particles formed at a series of applied pressures was determined and compression parameters were derived from the Heckel and Kawakita equations. The presence of PVP gave particles that were less prone to deform permanently during compression while the presence of surfactant gave particles that were less able to form tablets. In conclusion, the compression behaviour and tablet-forming ability of spray-dried amorphous lactose can be modulated by the addition of stabilising polymers or surfactants to the spray feed solution.

Compressive Strength↗

PubMed2003

Modelling of drug release from coated granular pellets.

A mathematical model of drug release from coated pellets with a granular core has been developed. The model includes a dynamic description of all three main processes contributing to drug release from such a system, i.e. liquid inflow, drug dissolution, and liquid efflux caused by diffusion across the coating. The cumulative fraction of released drug has been shown to be determined by three rate constants, one for each process mentioned above, together with two dimensionless parameters. These parameters are related to the porosity of the pellet core and the solubility of the drug in the dissolution medium. The model has been validated by comparison with experimentally determined release profiles for pellets consisting of a granular core of microcrystalline cellulose containing dispersed salicylic acid, coated by a thin layer of ethyl cellulose.

Delayed-Action Preparations↗

PubMed2003

Droplet and particle size relationship and shell thickness of inhalable lactose particles during spray drying.

To find means of controlling the size and density of particles intended for inhalation the relationship between droplet and particle size during spray drying was investigated. Lactose solutions were atomized with a two-fluid nozzle and dried in a laboratory spray drier. The effects of nozzle orifice diameter, atomization airflow and feed concentration on droplet and particle size were examined. Mass median diameter of both droplets and particles were analyzed with laser diffraction. In addition, scanning electron microscopy and transmission electron microscopy were used for studies of particle shape and morphology. It was demonstrated that nozzle orifice diameter and airflow, but not feed concentration controlled the droplet size during atomization. Increasing droplet size increased particle size but the effect was also influenced by feed concentration. Particles from solutions of a low concentration (1% w/w) were smaller than those from higher concentrations (5-20% w/w). This may be partly explained by lower yields at higher feed concentrations, but may also be related to differences in drying rate. Spray-dried lactose solutions formed hollow particles, and it was suggested that the shell thickness of the particles increased with increasing feed concentration.

Administration, Inhalation↗

PubMed2003

Drug release from reservoir pellets compacted with some excipients of different physical properties.

The aim of the present study was to investigate the influence of the size and the porosity of excipient microcrystalline cellulose (MCC) particles on the densification and the deformation during compaction and the consequent effect on the drug release from reservoir pellets. Drug pellets consisting of salicylic acid and microcrystalline cellulose were prepared by extrusion-spheronisation and spray-coated with ethyl cellulose (ethanol solution). Excipient pellets of different size and porosity were prepared by extrusion-spheronisation or direct spheronisation. Five binary mixtures of reservoir pellets and excipient particles were prepared in the proportion 1:7 and lubricated. After compaction the reservoir pellets were retrieved and analysed to determine the intragranular porosity, surface area, shape and drug release. The reservoir pellets were shown to undergo extensive deformation and densification during compaction, resulting in a preserved or even prolonged drug release time. The mode of deformation of the reservoir pellets seems to be critical for the compression-induced change in drug release. Formation of large indents has a negative effect on the release time, while the use of small particles or small deformable agglomerates has a protective effect. We also hypothesize that the coating structure changes during compaction and the final structure of the coating is the net effect of two parallel processes, one reducing and one prolonging the drug transport time across the coating.

Cellulose↗

PubMed2003

Effect of intragranular porosity on compression behaviour of and drug release from reservoir pellets.

In this study, reservoir pellets were prepared and their compression behaviour as well as the importance of their porosity for compression-induced changes in drug release was investigated. Pellets of three different porosities, consisting of microcrystalline cellulose and salicylic acid, were prepared by extrusion-spheronisation and spray-coated with ethyl cellulose (ethanol solution). Lubricated reservoir pellets were compressed and retrieved by deaggregation of the tablets. The retrieved pellets were analysed regarding porosity, thickness, surface area, shape and drug release. It was found that the coating did not significantly affect their compression behaviour. Compaction of pellets of high original porosity considerably affected densification and degree of deformation, whereas the effect on drug release was minor. For low porosity pellets the influence of compaction on drug release was appreciable, but only slight regarding densification and degree of deformation. In conclusion, the porosity of pellets is a potential factor that the formulator can use to optimize drug release and one that can affect the robustness of a formulation during manufacture. Moreover, the coating may be able to adapt to the densification and deformation of the pellets.

Algorithms↗

PubMed2003

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).

PURPOSE: 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.

Drug Stability↗

PubMed2003

A novel approach to derive a compression parameter indicating effective particle deformability.

In this article, a compression parameter is derived and its physical significance discussed. Tablets were formed from two sodium chloride powders and from two sucrose powders over a wide range of compaction pressures and the tensile strength and the porosity of the tablets were determined. From these data, the novel compression parameter and the Heckel parameter were calculated. Above a lower pressure threshold, the tablet strength increased relatively linear with compaction pressure up to 300-500 MPa and thereafter, the tablet strength leveled off. From the linear region, the compression parameter was derived. The tablet porosity data obeyed reasonably the Heckel function and from the linear region, the yield strength was calculated. For all four powders, a ratio between the compression parameter and the Heckel yield strength of about 3 was obtained. It is concluded that the suggested compression parameter represents an indication of the effective deformability of particles during compression which is suggested to correlate with the hardness of the particles.

Compressive Strength↗

PubMed2002

The influence of pellet shape and surface properties on the drug release from uncoated and coated pellets.

Pellets of different shape, varying from spherical to cylindrical, without and with film coating were tested for their drug release properties. For non-disintegrating uncoated pellets, drug release was found to be inversely related to the pellet porosity. A change of 5% in porosity doubled the value of the mean dissolution time (MDT). As coat thickness increased, the MDT value of coated pellets increased. For those pellets, which are nearly spherical, once a thickness of about 20 microm had been achieved, there was little further reduction in retardation. Pellets produced by extrusion/spheronisation appeared to prolong drug release to a larger extent than those where the extrusion step had been omitted. There was a strong inverse relationship between the surface area by volume of the coated pellets and the value of the MDT. The values of the relative dispersion coefficient (RD), which is an indicator of the drug release mechanism, were related to the amount of fluid used to manufacture the pellets and the pellet shape, in a similar fashion for both uncoated and coated pellets. This suggested that the presence of the film coating changed the rate but not the mechanism of drug release.

Algorithms↗

PubMed2002

The influence of pellet shape and film coating on the filling of pellets into hard shell capsules.

Pellets of different shape, varying from spherical to cylindrical, were filled into hard shell capsules. When no film coat was applied, the pellets had not to be perfectly spherical in order to be filled reproducibly. An aspect ratio of 1.2 or less appeared to be the threshold value. However, pronounced surface roughness hindered the filling process, and hence it appears necessary to monitor this parameter. After coating of the pellets with an ethylcellulose film, none of the batches could be filled to an acceptable standard, because electrostatic loading led to a blockage of the filling mechanism. However, the addition of 1% talcum powder was sufficient to remove all charges, and again filling became a function of the pellet shape, confirming the threshold aspect ratio value of 1.2.

Acetaminophen↗

PubMed2002

The influence of film coating on pellet properties.

There are numerous reasons for which film coatings are applied to pellet formulations; for example, controlled release, taste masking, and improved stability. The aim of this paper was to study the influence of pellet shape on the deposition of film coatings in a fluid-bed process by monitoring the pellet shape as a function of the film thickness formed. Eight pellet batches were used, of which four were spherical visually, and the other batches can be described as ovoids, dumbbells, long dumbbells, and cylinders. The average coat thickness of the pellets assessed by cross-section measurements did not appear to be influenced by the initial shape of the pellets. The fluid-bed process, however, had an impact especially for those pellets that had an aspect ratio greater than 1.5. The change in the pellet shape during film coating could only be monitored effectively employing a three-dimensional shape factor. Significant changes in shape occurred at the beginning of the coating process up to approximately the first 15 min, after which the shape remained constant.

Tablets↗