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- O'Mahony, M. A., et al.
(author)
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Investigation into the mechanism of solution-mediated transformation from FI to FIII carbamazepine : The role of dissolution and the interaction between polymorph surfaces
- 2013
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In: Crystal Growth and Design. - : American Chemical Society (ACS). - 1528-7505 .- 1528-7483. ; 13:5, s. 1861-1871
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Journal article (peer-reviewed)abstract
- The solution mediated polymorphic transformation (SMPT) of the pharmaceutical compound carbamazepine was investigated in ethanol. Bulk transformation experiments were performed by monitoring the solution concentration and polymorphic composition over time during the transformation from the metastable FI polymorph to the stable FIII polymorph for a variety of initial conditions. Microscopic techniques, single-crystal X-ray diffraction, and computational methods were used to analyze the transformation. The nucleating behavior of the stable FIII polymorph was a significant factor affecting the transformation time across the range of experiments. The surfaces of the metastable FI particles were responsible for the nucleation of FIII during the transformation. However, no specific lattice matching or epitaxy was conclusively identified. A modest amount of dissolution of the FI particles was found to favor the nucleation of FIII but where extensive dissolution or no significant dissolution occurred this had a negative effect on the nucleation of FIII.
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| 4. |
- O'Mahony, M., et al.
(author)
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Investigating the dissolution of the metastable triclinic polymorph of carbamazepine using in situ microscopy
- 2014
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In: CrystEngComm. - Royal Society of Chemistry (RSC)) : Royal Society of Chemistry (RSC). - 1466-8033. ; 16:20, s. 4133-4141
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Journal article (peer-reviewed)abstract
- Despite a tendency to undergo solution-mediated polymorphic transformation, the dissolution behaviour of the metastable FI (triclinic) polymorph of the pharmaceutical compound carbamazepine (CBZ) was investigated using in situ optical microscopy. Experiments were performed at an undersaturation where single crystals of the metastable FI polymorph dissolved. Dissolution in different solvents was investigated at a constant undersaturation. Separately the sublimation of FI was examined and additionally the dissolution was observed at undersaturations where the more stable FIII polymorph crystallized. The results show that both the dissolution and sublimation of FI occur primarily in the direction of the a-axis of the FI crystal structure where the CBZ molecules are found to stack in this direction. The order for the dissolution rate of FI was acetonitrile ≥ methanol > ethanol. The order of the dissolution rates in each of the solvents is inversely correlated to the viscosity and the binding energy of the solvents with the (100) surface of FI in each of the solvents. This suggests that the rate determining step for the dissolution may be either the diffusion or the detachment of CBZ molecules from the surface of FI. A notable difference in dissolution behaviour is also observed at undersaturations where the more stable FIII polymorph nucleates and grows.
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| 5. |
- Croker, D. M., et al.
(author)
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Nucleation in the p-toluenesulfonamide/triphenylphosphine oxide co-crystal system
- 2013
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In: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 13:8, s. 3754-3762
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Journal article (peer-reviewed)abstract
- Nucleation has been studied in pure co-crystal and mixed co-crystal phase regions of the ternary phase diagram (TPD) in acetonitrile at 20 C using cooling crystallization experiments. Direct nucleation of each of the co-crystal phases in this system was independently observed in regions of the TPD where each is stable. In mixed regions, regions where either a co-crystal and a coformer, or both co-crystals, are stable, the phase that initially nucleated was a function of the mass composition in that region. The relative amount of each phase nucleating could be controlled by adjusting the relative mass fraction of each component. The kinetic return to equilibrium was also observed as the systems were held over time, with the selected mass fractions always returning to the equilibrium dictated by the TPD after 24 h
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| 6. |
- Croker, D. M., et al.
(author)
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Solution mediated phase transformations between co-crystals
- 2013
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In: CrystEngComm. - : Royal Society of Chemistry. - 1466-8033. ; 15:11, s. 2044-2047
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Journal article (peer-reviewed)abstract
- A solution mediated transformation between two co-crystal phases has been observed for the p-toluensulfonamide-triphenylphosphine oxide co-crystal system. This system has two known co-crystals with 1 : 1 and 3 : 2 stoichiometry respectively, and the ternary phase diagram (TPD) for the system has been determined in acetonitrile previously. By manipulating the solution composition in this solvent to a region of the TPD where the 1 : 1 co-crystal is stable, the 3 : 2 co-crystal could be observed to convert to the 1 : 1 co-crystal. The corresponding transformation was true for the 1 : 1 co-crystal in a region of the TPD where the 3 : 2 co-crystal is stable; the 1 : 1 co-crystal converted to the 3 : 2 co-crystal.
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| 7. |
- Maher, Anthony, et al.
(author)
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Investigation of the Solid-State Polymorphic Transformations of Piracetam
- 2012
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In: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 12:12, s. 6223-6233
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Journal article (peer-reviewed)abstract
- The solid-state polymorphic transformations of 2-oxo-1-pyrrolidine acetamide (piracetam) were investigated using a combination of off-line and online techniques: differential scanning calorimetry (DSC), high temperature X-ray diffraction (HT-XRD), thermal analysis, and hot-stage optical microscopy. Form II and Form III were each observed to transform directly to Form I upon heating, with Form II transforming at a slightly lower temperature. The transformation of both polymorphs to Form I was observed to cause physical cracking of the crystals as well as changing the optical properties. Form I consistently transformed to Form II when cooled. The molecular rearrangements required for the transformation from Form I to Form II were found to be more energetically favorable than those required for the transformation to Form III. The transformation from the metastable Form II to the stable Form III was not observed in the solid-state, while the Form II-Form III transition temperature was found to be higher than the transition temperature of both polymorphs to Form I.
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| 8. |
- Maher, Anthony, et al.
(author)
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Solution-mediated polymorphic transformation : Form II to Form III piracetam in organic solvents
- 2014
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In: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 14:8, s. 3967-3974
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Journal article (peer-reviewed)abstract
- The solution-mediated polymorphic transformation from Form II to Form III 2-oxo-1-pyrrolidine acetamide (piracetam) was investigated in seven organic solvents over the temperature range of 5–50 °C. The transformation rate increased as a function of temperature, agitation, and the solubility of piracetam in the host solvent. However, this trend was reversed in 2-propanol. Molecular modeling demonstrated that 2-propanol forms interactions with piracetam molecules in solution stronger than those formed by other solvents, thereby retarding the nucleation and growth of FIII(6.525) during the transformation in this solvent.
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- Cheuk, Dominic, et al.
(author)
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Investigation into solid and solution properties of quinizarin
- 2015
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In: CrystEngComm. - : Royal Society of Chemistry. - 1466-8033. ; 17:21, s. 3985-3997
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Journal article (peer-reviewed)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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| 10. |
- Dick, FD, et al.
(author)
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Environmental risk factors for Parkinson's disease and parkinsonism : The Geoparkinson study
- 2007
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In: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 64:10, s. 666-672
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Journal article (peer-reviewed)abstract
- Objective: To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. Methods: A case-control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. Results: Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure-response relationship for pesticides (low vs no exposure, odds ratio (OR) =1.13, 95% Cl 0.82 to 1.57, high vs no exposure, OR =1.41, 95% Cl 1.06 to 1.88) and ever knocked unconscious (once vs never, OR= 1.35, 95% Cl 1.09 to 1.68, more than once vs never, OR = 2.53, 95% Cl 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% Cl 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. Conclusions: The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.
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