| 1. |
- Alander, Eva M., et al.
(author)
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Agglomeration and adhesion free energy of paracetamol crystals in organic solvents
- 2007
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In: AIChE Journal. - : Wiley. - 0001-1541 .- 1547-5905. ; 53:10, s. 2590-2605
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Journal article (peer-reviewed)abstract
- The agglomeration of paracetamol during crystallization in different pure solvents has been investigated. Narrowly sieved crystals were suspended as seeds and allowed to grow and agglomerate at constant supersaturation and temperature. Particles from each experiment were examined by image analysis and multivariate data evaluation, for the number of crystals per particle. From the resulting number distribution, parameters defining the degree of agglomeration were extracted. The degree of agglomeration among the product particles is fairly low in water, methanol, and ethanol, while it is substantial in acetone particularly, but also in acetonitrile and methyl ethyl ketone. Surfaces of large, well-grown paracetamol crystals have been characterized by contact angle measurements. The surface free energy components of different crystal faces have been estimated using Lifshitz-van der Waals acid-base theory. The data are used for estimation of the solid-liquid interfacial free energy of each face in the solvents of the agglomeration experiments and the corresponding crystal-crystal adhesion free energy of pairs of faces. The degree of agglomeration in different solvents does correlate to the free energies of adhesion. This supports the hypothesis that the influence of the solvent on the crystal agglomeration relates to physico-chemical adhesion forces between crystal faces in the solution.
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| 2. |
- Alander, E. M., et al.
(author)
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Mechanisms of crystal agglomeration of paracetamol in acetone-water mixtures
- 2005
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In: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 0888-5885 .- 1520-5045. ; 44:15, s. 5788-5794
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Journal article (peer-reviewed)abstract
- The mechanisms governing the influence of the solvent composition on the agglomeration in a crystallization process have been investigated. Narrowly sieved paracetamol crystals were suspended in supersaturated acetone-water solutions, and were allowed to grow at isothermal conditions, after which the agglomeration was recorded. In all experiments the same sieve size fraction was used as well as the same magma density. In each experiment the supersaturation was kept constant. Experiments were performed in different solvent compositions at different supersaturation, crystal growth rate, solution viscosity, and agitation rate. For a statistically sufficient number of particles from each experiment, the number of crystals in each product particle was determined by image analysis and multivariate data evaluation. From the resulting number distributions of crystals per product particle, parameters defining the degree of agglomeration were extracted. The experimental results clearly establish that there is an influence of the solvent composition on the degree of agglomeration, which cannot be explained by differences in crystal growth rate, or differences in solution viscosity. The degree of agglomeration is found to decrease with increasing solvent polarity. It is, suggested that the mechanism by which the solvent influence relates to the crystal-solvent interaction and the physicochemical. adhesion forces between crystals in the solution.
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| 3. |
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| 4. |
- Fichtner, Frauke, et al.
(author)
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Effect of preparation method on compactability of paracetamol granules and agglomerates
- 2007
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 336:1, s. 148-158
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Journal article (peer-reviewed)abstract
- 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.
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| 5. |
- Fichtner, Frauke, 1975-
(author)
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Identification and Variation of some Functionality Related Characteristics of Pharmaceutically Relevant Solid Materials and their Effect on Product Performance
- 2007
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to identify some functionality related characteristics of pharmaceutically relevant solid materials and to study the effect of their variation on processing behaviour and product performance. For this purpose, particles with different characteristics were prepared under a variety of conditions by crystal agglomeration, wet granulation and spray drying. The effect of particle size distribution on the evolution of the tablet microstructure during and after compression was investigated. The compression behaviour of particles with different nominal strength and degrees of agglomeration was studied and the influence of the surfactant concentration of amorphous particles on the compression behaviour was examined. The response of the powders to compression was described with the help of various techniques characterising the microstructure and tensile strength of the tablets produced. Furthermore, a method suitable for observing drug release from single matrix granules was developed and used to study the effect of granule porosity and compaction pressure on the drug release process. The particle size distribution did not influence the evolution of the tablet porosity or the tensile strength during compression, but it could have an effect on the evolution of the tablet microstructure during short-term storage, depending on the instability mechanism. The compression behaviour of particles prepared by crystal agglomeration and wet granulation was dependent on their degree of agglomeration and their failure strength. For particles with similar solid state properties and compression behaviour, the surface energy appears to have an effect on the bonding strength of adsorption bonds acting at interparticulate junctions. Using the method developed to observe the drug release from single matrix granules, reproducible data was obtained enabling the drug release process to be characterised. Depending on the type of matrix and the compaction pressure, the drug release rate could be enhanced or retarded.
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| 6. |
- Fichtner, Frauke, et al.
(author)
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Particle size distribution and evolution in tablet structure during and after compaction
- 2005
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 292:02-jan, s. 211-225
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Forsberg, Kerstin, et al.
(author)
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Crystal growth kinetics of iron fluoride trihydrate
- 2006
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In: Journal of Crystal Growth. - Royal Inst Technol, Dept Chem Engn & Technol, KTH, S-10044 Stockholm, Sweden. : Elsevier BV. - 0022-0248 .- 1873-5002. ; 296:2, s. 213-220
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Journal article (peer-reviewed)abstract
- Crystal growth of beta-FeF3 • 3H(2)O has been investigated in mixtures of 3 mol kg(-1) hydrofluoric acid and 3 mol kg(-1) nitric acid at 30, 40 and 50 degrees C. Seeded isothermal desupersaturation experiments have been performed in the range: 1.3 < S < 3.6. Solution samples were analysed for total iron concentration with inductively coupled plasma atomic emission spectroscopy. The true supersaturation driving force was estimated by a proper speciation using the software SSPEC using appropriate stability constants. Growth rate parameters of the BCF surface diffusion growth rate equation and the empirical power-law equation have been estimated by fitting the supersaturation balance equation using a nonlinear optimization procedure. The results show that the growth rate is surface integration controlled. The growth rate at a supersaturation ratio of 2 was found to be 3.5 x 10(-12) m s(-1) at 30 degrees C, 7.4 x 10(-12) m s(-1) at 40 degrees C and 16 x 10(-12) m s(-1) at 50 degrees C. The activation energy of the rate constant of crystal growth was found to be 61 kJ mol(-1). .
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| 8. |
- Forsberg, Kerstin, 1979-
(author)
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Crystallization of Metal Fluoride Hydrates from Mixed Acid Solutions
- 2009
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Doctoral thesis (other academic/artistic)abstract
- In this work crystal growth and nucleation of b-FeF3×3H2O and crystallization of chromium (III), iron (III) and nickel (II) fluoride hydrates from mixed acid (1-3 mol/kg HNO3 and 1-6 mol/kg free HF) have been investigated. The solubility of b-FeF3×3H2O has been determined in solutions of different hydrofluoric acid (1-7mol/ kg) and nitric acid (0-7mol/ kg) concentrations at 30, 40 and 50°C. The total iron concentration at equilibrium ranges from about 1 to 35 g/kg solution. In the range of investigated conditions the solubility in terms of total iron content increases with increasing temperature and decreases with increasing concentration of hydrofluoric acid and nitric acid. The results are analysed by examining the chemical speciation in the solutions. The crystal growth kinetics of b-FeF3×3H2O crystals have been studied by performing seeded isothermal desupersaturation experiments in solutions of 1.5-3.0 mol/ kg nitric acid and 1.4- 5.6 mol/ kg free hydrofluoric acid at 30, 40 and 50°C. The results show that the crystal growth is surface integration controlled. When the driving force is based on a proper speciation no clear correlation of the growth rate with hydrofluoric acid or nitric acid concentration is found. The rate is about the same in industrial pickle liquor as in pure acid solutions. The growth rate at a supersaturation ratio (c(FeF3)free/cs(FeF3)free) of 2 was found to be 5.2×10-12m/s at 30°C, 7.9×10-12m/s at 40°C and 20×10-12m/s at 50°C. Thus, the crystal growth rate at 50°C is about four times higher than at 30°C. The temperature dependence of the rate constant corresponds to an activation energy of 55kJ/ mol. Crystallization from solutions supersaturated with both Cr(III) and Fe(III) has been investigated and it has been observed that Fe(III) and Cr(III) crystallizes in the form of Cr(Fe)F3×3H2O which is isostructural with CrF3×3H2O. Iron(III) and nickel(II) crystallizes into an unidentified fluoride hydrate crystal. The crystal growth rate of CrF3×3H2O at 50°C is about the same as the growth rate of b-FeF3×3H2O crystals.
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| 9. |
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| 10. |
- Forsberg, Kerstin, et al.
(author)
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Recycling of waste pickle acid by precipitation of metal fluoride hydrates
- 2007
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In: Minerals Engineering. - : Elsevier BV. - 0892-6875 .- 1872-9444. ; 20:9, s. 950-955
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Journal article (peer-reviewed)abstract
- Stainless steel is pickled in mixed acid solutions (1-3 M HNO3 and 0.5-4 M HF). The spent solution is usually neutralized with lime, and in Sweden about 18,000 tons/yr of metal hydroxide sludge is disposed as landfill waste. We are developing a cost-saving and environmentally friendly process, involving crystallization of beta-FeF3 . 3H(2)O, where the metal content is recovered and the acid is recycled. Iron has been successfully separated from spent pickle bath solutions by precipitation of beta-FeF3 . 3H(2)O in a continuous crystallizer (10 L scale) where the solution is concentrated by nanofiltration. The crystal growth rate of beta-FeF3 . 3H(2)O has been determined in industrial pickle bath solutions at 50 degrees C and the results have been compared to previous measurements in pure HF/HNO3 solutions prepared in the laboratory. The growth rate of beta-beta eF(3) . 3H(2)O crystals at 50 degrees C is in the order of 10(-11) m/s in both industrial and pure acid mixtures.
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