| 1. |
- Alander, E. M., et al.
(författare)
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Characterization of paracetamol agglomerates by image analysis and strength measurement
- 2003
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Ingår i: Powder Technology. - : Elsevier BV. - 0032-5910 .- 1873-328X. ; 130:1-3, s. 298-306
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Tidskriftsartikel (refereegranskat)abstract
- Paracetamol is crystallized in different solvents and techniques are developed and used to characterize the product. The product particles from three different solvent compositions: ethylene glycol, acetone and an acetone-water mixture (30-70 wt.%) have been examined. Product properties visually observed are quantified by image analysis and evaluation of measured image descriptors with Principal Component Analysis (PCA). The agglomerate strength has been determined by crushing single agglomerates. Depending on the solvent, the content of single crystals and agglomerates differ. Agglomerates differ by the number and size of crystals grown together, as well as by the strength.
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| 2. |
- Gracin, Sandra, et al.
(författare)
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Polymorphism and Crystallization of p-Aminobenzoic Acid
- 2004
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 4:5, s. 1013-1023
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Tidskriftsartikel (refereegranskat)abstract
- p-Aminobenzoic acid (PABA) crystallizes in two different polymorphic forms: the alpha-polymorph, which is the commercially available form and appears as long, fibrous needles, and the beta-polymorph, which appears in the form of prisms. The thermodynamic stability and crystallization from different solvents have been studied experimentally. The system is found to be enantiotropic with a transition temperature of 25degreesC, below which the beta-form is the stable polymorph. The compound has been crystallized from 13 different solvents, either by slow cooling after which the product is allowed to mature in suspension, or by rapid cooling followed by immediate isolation. Needles were obtained from all solvents by both methods. In water and in ethyl acetate, at slow cooling below 20degreesC, the prismatic beta-form is obtained, however, often together with the needles. The beta-form crystals usually needed hours or days to grow at the very slow cooling used, while needles usually appeared in seconds. By careful control of supersaturation and temperature, cooling crystallization can be performed to produce the pure beta-form in water and in ethyl acetate. The influence of the solvent is explained by analysis of the crystal structures versus the possible interaction of the solvent molecules with the solute in solution. The alpha-form structure is governed by carboxylic acid dimers and is kinetically favored since it is believed that the corresponding dimers easily form in the solution, especially in less polar solvents.
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| 3. |
- Gracin, Sandra, et al.
(författare)
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Prediction of Solubility of Solid Organic Compounds in Solvents by UNIFAC
- 2002
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Ingår i: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 0888-5885 .- 1520-5045. ; 41:20, s. 5114-5124
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Tidskriftsartikel (refereegranskat)abstract
- Predictions of solubility of nine different solid organic fine chemical compounds in water and organic solvents of relevance to industrial processing are examined. UNIFAC interaction parameters are taken from standard reference literature, extracted from liquid-vapor equilibria. For most systems, predicted solubilities deviate more than 15% from experimental values. Deviations are due to uncertainties in the estimation of the activity of the pure solid as well as to deficiencies in the estimation of activity coefficients in the solution. By comparison with results from ab initio quantum chemical calculations of the elecrostatic potential on the molecular surface of the solutes, it can be shown that a key assumption of the UNIFAC approach is not necessarily fulfilled. The properties of a functional group may depend significantly on the properties of the rest of the molecule.
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| 4. |
- Gracin, Sandra, et al.
(författare)
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Solubility of Phenylacetic Acid, p-Hydroxyphenylacetic Acid, p-Aminophenylacetic Acid, p-Hydroxybenzoic Acid, and Ibuprofen in Pure Solvents
- 2002
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Ingår i: Journal of Chemical and Engineering Data. - : American Chemical Society (ACS). - 0021-9568 .- 1520-5134. ; 47:6, s. 1379-1383
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Tidskriftsartikel (refereegranskat)abstract
- The solubility of phenyl acetic acid, p-hydroxyphenylacetic acid, p-aminophenylacetic acid, p-hydroxybenzoic acid, and ibuprofen in water and in a range of organic solvents of relevance to industrial processing is reported. The solvents used are water, methanol, ethanol, 2-propanol, acetone, 4-methyl-2-pentanone, ethyl acetate, chloroform, and toluene. Solubility data are discussed from the standpoint of molecular aspects of solute-solvent interactions and by estimated solid-phase activity.
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| 5. |
- Granberg, R. A., et al.
(författare)
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Primary nucleation of paracetamol in acetone-water mixtures
- 2001
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Ingår i: Chemical Engineering Science. - : Elsevier BV. - 0009-2509 .- 1873-4405. ; 56:7, s. 2305-2313
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Tidskriftsartikel (refereegranskat)abstract
- The influence of solvent composition on primary nucleation of 4-hydroxyacetanilide (paracetamol) in acetone-water mixtures is investigated. The induction time for primary nucleation is determined, at various degrees of supersaturation and at different temperatures, in different solvent mixture compositions. Supersaturation is generated by the addition of water. and the homogeneous, agitated, isothermal solution is allowed to nucleate. The supersaturation driving force is calculated as the difference in the chemical potential. At equal thermodynamic driving force, the induction time depends on the composition of the solvent mixture. The interfacial energy is in the range 1-3 mJ/m(2) and tends to increase with decreasing solubility, i.e. increasing water content. The interfacial energy is slightly lower than a value calculated from a contact angle measurement (5 mJ/m(2)) in pure water and is significantly lower than values predicted by equations derived From simplified theories.
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| 6. |
- Granberg, R. A., et al.
(författare)
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Solubility of paracetamol in binary and ternary mixtures of water + acetone + toluene
- 2000
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Ingår i: Journal of Chemical and Engineering Data. - : American Chemical Society (ACS). - 0021-9568 .- 1520-5134. ; 45:3, s. 478-483
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Tidskriftsartikel (refereegranskat)abstract
- The solubility of paracetamol (4-hydroxyacetanilide) in binary mixtures of acetone + water and acetone + toluene and in ternary mixtures of water + acetone + toluene is reported. The temperature range is -5 to +30°C. In acetone + water the solubility increases to a maximum at approximately 25 mass % water before decreasing to a much lower value in pure water as compared to pure acetone. In acetone + toluene the solubility decreases monotonically with increasing toluene concentration. The water content has a strong influence also in ternary mixtures. Activity coefficients in the saturated solutions are estimated.
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| 7. |
- Lindberg, M., et al.
(författare)
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Reaction crystallization in strained fluid films
- 2001
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Ingår i: Chemical Engineering Science. - : Elsevier BV. - 0009-2509 .- 1873-4405. ; 56:10, s. 3257-3273
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Tidskriftsartikel (refereegranskat)abstract
- The detailed conditions during the ultimate stage of micromixing of the reactants in a reaction crystallization process are analysed. A mathematical model is developed to describe mass transfer, chemical reaction, and crystallization of a molecular compound in strained lamellar structures of reactant solutions inside the smallest vortices. The numerical calculations show that the supersaturation varies significantly in space and time, and suggest that significant crystallization may occur inside these vortices in the case of low-soluble and sparingly soluble compounds. At the end of the vortex lifetime, the crystal size distribution is quite dependent on the properties of the system and on the processing conditions. The number of crystals generated correlates strongly to the maximum supersaturation occurring during the vortex lifetime, and this maximum supersaturation is as a first approximation well described by simplified mass transfer models where crystallization is neglected. Often a significant supersaturation remains at the end of the vortex lifetime and the size of the crystals leaving the vortex is determined by the growth rate rather than by nucleation and mass constraint. The mean size is usually larger than the limiting size for Ostvald ripening in the bulk and the size distribution is quite narrow. The results show that neglect of the detailed conditions in reaction crystallization of a molecular compound may not be justified.
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| 8. |
- Lindberg, M., et al.
(författare)
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Supersaturation generation at the feed point in reaction crystallization of a molecular compound
- 2000
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Ingår i: Chemical Engineering Science. - 0009-2509 .- 1873-4405. ; 55:10, s. 1735-1746
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Tidskriftsartikel (refereegranskat)abstract
- The maximum product concentration of a molecular compound at the feed point in reaction crystallization is analysed by modelling. A model describing unsteady mass transfer and chemical reaction in strained, semi-infinite, fluid films is combined with models describing productivity constraints and reactant concentration changes during the course of a process. The maximum product concentration is taken as a first estimate of the maximum supersaturation and is used as a basis to discuss the product crystal size that may be produced. The result suggests that at certain conditions we may find smaller product crystals at decreased reactant concentrations. The maximum concentration varies during the course of a single-feed semibatch process and the highest value is not necessarily found in the beginning. The variation with time, depends on the choice of the reactant to feed, and the results provide an explanation to why the product crystal mean size may depend on the choice of feed reactant. Guidelines are proposed for how to decide on optimum reactant solution concentrations and for how to select the reactant to feed in a semibatch process. In addition it is suggested that larger crystals may be produced if the feed reactant concentration is low early in the process and is allowed to gradually increase with time in a controlled way. The term programmed feed concentration'' is introduced.
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| 9. |
- Nordström, Fredrik, et al.
(författare)
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Analysis of solution nonideality of a pseudomorphic drug system through a comprehensive thermodynamic framework for the design of a crystallization process
- 2004
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 93:4, s. 995-1004
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Tidskriftsartikel (refereegranskat)abstract
- Solutions of a semipolar drug belonging to the alpha(v) beta(iii) integrin antagonist class of compounds were studied in a comprehensive thermodynamic framework. The solubility of two pseudomorphic forms (an anhydrate and a monohydrate) was measured at several temperatures and various solvent mixtures of acetonitrile and water. Both forms displayed a bell-shaped solubility behavior as a function of cosolvent composition. Thermodynamic framework used to analyze the data comprised van't Hoff and enthalpy-entropy compensation analyses. The two pseudomorphs exhibited linear temperature dependence from 25 to 65degreesC at all solvent compositions (i.e., ideal behavior with temperature for fixed solvent composition). Plots of enthalpy of solublization and Gibbs free energy showed two distinct regions with contrasting thermodynamic, and consequently, underlying structural properties (indicating non-deal behavior with solvent composition for a fixed temperature). Solubility increased due to entropy effects in the acetonitrile rich region, whereas enthalpy effects dominated solublization in the water-rich region. Quantification of this phenomenon by plotting DeltaH versus DeltaG showed considerable nonlinearity, and that the two regions were separated by a significant discontinuity-a trend rarely seen before in the literature. The reason behind this behavior is believed to be due to the complex interactions in the solution of the drug in water acetonitrile solvent system. A very significant aspect of the comprehensive thermodynamic analysis is that it helped explain the puzzling feature of the data, which showed that the free energy of phase transformation between the two pseudomorphic forms for a given temperature was not independent of the solvent composition. The resulting explanation has major consequences for crystallization process development.
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| 10. |
- Pino-Garcia, Osvaldo, et al.
(författare)
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Influence of additives on nucleation of vanillin : Experiments and introductory molecular simulations
- 2004
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 4:5, s. 1025-1037
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Tidskriftsartikel (refereegranskat)abstract
- Nucleation of vanillin (VAN) in 2-propanol/water in the presence of additives, viz., acetovanillone (AVA), ethyl vanillin (EVA), guaiacol (GUA), guaethol (GUE), 4-hydroxyacetophenone (HAP), 4-hydroxybenzaldehyde (HBA), and vanillic acid (VAC) is investigated experimentally and by molecular simulations. In the experimental work, the induction time for nucleation is measured at different temperatures and levels of supersaturation using a multicell apparatus. A large variation in the experimental data is observed, and this variation is analyzed by statistical methods. By classical nucleation theory, the induction time data are used to estimate the solid-liquid interfacial energy of vanillin for each VAN-additive system. At 1 mol %, the interfacial energy becomes lower in the presence of AVA, EVA, HAP, and VAC, while it becomes higher in the presence of the other additives. As the additive concentration increases from 1 to 10 mol %, the interfacial energy also increases. The interfacial energy ranges from 6.9 to 10.1 mK m(-2). Molecular modeling, implemented in the program Cerius2, is used to simulate and examine the surface chemistry of the likely crystal growth faces of VAN (i.e., {001} and {100}). To evaluate the additive-crystal face interaction energy, two approaches are used: the surface adsorption method and the lattice integration method. Both experimental and molecular simulation results indicate that the additives studied are potential modifiers of the nucleation of VAN. However, a simple and clear relationship between the experimental values of interfacial energy and the calculated interaction energies for the most important crystal faces of VAN cannot be identified. The modeling does not concern the actual nucleation but rather the conditions of a growing surface and are based on several severe simplifications. Obviously, this simplistic approach does not sufficiently capture the influence of additives on the nucleation of vanillin.
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