| 1. |
- Cheuk, Dominic, et al.
(författare)
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Influence of solvent on crystal nucleation of benzocaine
- 2020
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Ingår i: CrystEngComm. - : Royal Society of Chemistry (RSC). - 1466-8033. ; 22:48, s. 8330-8342
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Tidskriftsartikel (refereegranskat)abstract
- The influence of the solvent in nucleation of a polymorphic organic molecule, benzocaine, has been explored by measuring nucleation induction times, probing solvent-solute interactions in solution with spectroscopy and modelling the strength of solvent-solute intermolecular interactions using density functional theory (DFT). Over 2640 induction time experiments were conducted to study the crystal nucleation of benzocaine FII in six different organic solvents. The nucleation driving force required to reach the same induction time is strongly solvent-dependent, increasing in the order: ethyl acetate < 1,4-dioxane < acetonitrile < methanol < n-butanol. Nucleation in toluene is reasonably easy but the exact position varies with the induction time. The order between the solvents overall corresponds to the order of increasing interfacial energy as determined within the classical nucleation theory. The shift of the FTIR carbonyl frequency reflecting the strength in the solvent-solute interaction decreases in the same order as the interfacial energy of benzocaine FII increases. This shift is corroborated by DFT calculated energies of binding one solvent molecule to the carboxyl group of benzocaine. An even better correlation of the influence of the solvent on the nucleation is provided by DFT calculated energy of binding the complete first solvation shell to the benzocaine molecule. The different methods reveal a consistent picture and suggest that the stronger the solvent binds to the benzocaine molecule in solution, the slower the nucleation becomes.
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| 2. |
- Cheuk, Dominic, et al.
(författare)
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Investigation into solid and solution properties of quinizarin
- 2015
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Ingår i: CrystEngComm. - : Royal Society of Chemistry. - 1466-8033. ; 17:21, s. 3985-3997
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphism, crystal shape and solubility of 1,4-dihydroxyanthraquinone (quinizarin) have been investigated in acetic acid, acetone, acetonitrile, n-butanol and toluene. The solubility of FI and FII from 20 degrees C to 45 degrees C has been determined by a gravimetric method. By slow evaporation, pure FI was obtained from n-butanol and toluene, pure FII was obtained from acetone, while either a mixture of the two forms or pure FI was obtained from acetic acid and acetonitrile. Slurry conversion experiments have established an enantiotropic relationship between the two polymorphs and that the commercially available FI is actually a metastable polymorph of quinizarin under ambient conditions. However, in the absence of FII, FI is kinetically stable for many days over the temperature range and in the solvents investigated. FI and FII have been characterized by infrared spectroscopy (IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission and ordinary powder X-ray diffraction (PXRD) at different temperatures. The crystal structure of FII has been determined by single-crystal XRD. DSC and high-temperature PXRD have shown that both FI and FII will transform into a not previously reported hightemperature form (FIII) around 185 degrees C before this form melts at 200-202 degrees C. By indexing FIII PXRD data, a triclinic P (1) over bar cell was assigned to FIII. The solubility of quinizarin FI and FII in the pure organic solvents used in the present work is below 2.5% by weight and decreases in the order: toluene, acetone, acetic acid, acetonitrile and n-butanol. The crystal shapes obtained in different solvents range from thin rods to flat plates or very flat leaves, with no clear principal difference observed between FI and FII.
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| 3. |
- Cheuk, Dominic, et al.
(författare)
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Thermodynamics of the Enantiotropic Pharmaceutical Compound Benzocaine and Solubility in Pure Organic Solvents
- 2020
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 109:11, s. 3370-3377
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Tidskriftsartikel (refereegranskat)abstract
- The thermodynamic relationship between FI and FII of ethyl 4-aminobenzoate (benzocaine) has been investigated. Slurry conversion experiments show that the transition temperature below which FI is stable is located between 302 K-303 K (29 degrees C-30 degrees C). The polymorphs FI and FII have been characterised by infrared spectroscopy (IR), Raman spectroscopy, transmission powder X-ray diffraction (XRPD) and differential scanning calorimetry (DSC). The isobaric solid state heat capacities have been measured by DSC. The quantitative thermodynamic stability relationship has been determined in a comprehensive thermodynamic analysis of the calorimetric data. The solubility of both polymorphs has been determined in eight pure organic solvents over the temperature range 278 K-323 K by a gravimetric method. The mole fraction solubility of benzocaine decreases in the order: 1,4-dioxane, acetone, ethyl acetate, chloroform, acetonitrile, methanol, n-butanol and toluene. Comparison with the determined activity of solid benzocaine forms shows that negative deviation from Raoult's law ideality is found in dioxane, acetone and ethyl acetate solutions, and positive deviation in solutions of the other investigated solvents.
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| 4. |
- Svärd, Michael, Dr, 1976-, et al.
(författare)
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Solute clustering in undersaturated solutions systematic dependence on time, temperature and concentration
- 2018
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 20:22, s. 15550-15559
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Tidskriftsartikel (refereegranskat)abstract
- Molecular clustering and solvent-solute interactions in isopropanol solutions of fenoxycarb have been thoroughly and systematically investigated by dynamic light scattering, small-angle X-ray scattering, and nanoparticle tracking, supported by infrared spectroscopy and molecular dynamics simulations. The existence of molecular aggregates, clusters, ranging in size up to almost a micrometre is clearly recorded at undersaturated as well as supersaturated conditions by all three analysis techniques. The results systematically reveal that the cluster size increases with solute concentration and time at stagnant conditions. For most concentrations the time scale of cluster growth is of the order of days. In undersaturated solutions the size appears to eventually reach a maximum value, higher the higher the concentration. Below a certain concentration threshold clusters are significantly smaller. Clusters are found to be smaller in solutions pre-heated at a higher temperature, which offers a possible explanation for the so-called "history of solution'' effect. The cluster distribution is influenced by filtration through membranes with a pore size of 0.1 mm, offering an alternative explanation for the "foreign particle-catalysed nucleation'' effect. At moderate concentrations larger clusters appear to be sheared into smaller ones, but the original size distribution is rapidly re-established. At higher concentrations, although still well below solubility, the cluster size as well as solute concentration are strongly affected, suggesting that larger clusters contain at least a core of more organized molecules not able to pass through the filter.
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