Influence of Solution Thermal and Structural History on the Nucleation of m -Hydroxybenzoic Acid Polymorphs

2014

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Nearly 1800 induction time experiments have been performed on crystal nucleation of fenoxycarb in isopropanol to investigate the influence of solution pretreatment. For each preheating temperature and preheating time, at least 80 experiments were performed to obtain statistically valid results. The relationship between the inverse of the induction time and the preheating time can be reasonably described as an exponential decay having time constants ranging up to days depending on the temperature. This dependence on the preheating temperature corresponds to an activation energy of over 200 kJ/mol. Given sufficiently long preheating time and high temperature, the solution appears to reach a steady-state where the "memory" effect has disappeared. Density functional theory modelling suggests that the molecular packing in the crystal lattice is not the thermodynamically stable configuration at the level of simple dimers in solution, while modelling of the first solvation shell reveals that solute aggregation must exist in solution due to the low solvent to solute molecular ratio. It is thus hypothesized that the dissolution of crystalline material at first leaves molecular assemblies in solution that retain features of the crystalline structure which facilitates subsequent nucleation. However, the longer the solution is kept at a temperature above the saturation temperature and the higher the temperature, the more these assemblies disintegrate, and transform into molecular structures less suited to form critical nuclei..

Section: Methodsmentioning

confidence: 99%

Influence of History of Solution in Crystal Nucleation of Fenoxycarb: Kinetics and Mechanisms

Kuhs

Żegliński

2014

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“…Each batch was kept at an elevated temperature of 60 °C for 6 h, and then at 55 °C for another 6-10 h, in order to standardize the pre-treatment of solutions and minimize effects of solution history 16,24 . The test tubes were then cooled at a constant cooling rate of either 3 °C/h or 10 °C/h.…”

Section: Nucleation Experimentsmentioning

confidence: 99%

“…The structure of the thermodynamically stable polymorph at room temperature 12 , henceforth termed form I, contains the carboxylic acid dimer motif packed in the common herring-bone pattern, whereas that of the metastable polymorph, form II, features intermolecular hydrogen bond chains involving alternate COOH and OH-groups, creating layers of ribbons where the non-polar regions of neighbouring ribbons interact through van der Waals' forces. In a previous contribution we gave an account of experiments probing the influence of the thermal and structural history of solution on the nucleation of mHBA polymorphs in ethyl acetate solution 16 . Here, we report a quantitative investigation into the thermodynamic properties of both polymorphs, and into the nucleation behaviour in five different solvents.…”

Section: Introductionmentioning

confidence: 99%

m-Hydroxybenzoic Acid: Quantifying Thermodynamic Stability and Influence of Solvent on the Nucleation of a Polymorphic System

Svärd

2013

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Nucleation of m-hydroxybenzoic acid crystals in different pure solvents has been investigated, and the thermodynamic interrelationship between two polymorphs analysed. The melting properties and specific heat capacities of both polymorphs have been determined by differential scanning calorimetry and the solubility in several solvents at different temperatures measured gravimetrically. Absolute values of the Gibbs free energy, enthalpy and entropy of fusion, and the activity of the polymorphs have been determined as functions of temperature. It is established that the polymorphs are monotropically related, with differences in enthalpy and Gibbs free energy of approximately one kJ/mol at room temperature. In a total of 539 nucleation experiments, in six solvents and with different cooling rates, the visible onset of nucleation was recorded and the nucleating polymorph isolated. It is found that the degree of supersaturation required for nucleation and the polymorphic outcome depend strongly on the solvent. The metastable polymorph is kinetically favoured under all evaluated experimental conditions, and for most of the conditions it is also statistically the most probable outcome. Nucleation of the stable polymorph is increasingly promoted in solvents of increasing solubility. It is shown how this can be rationalized by analysis of solubility and rate of supersaturation generation.

“…This technique of recording the induction time has been evaluated in smaller scale for these systems in previous contributions 4,5 and has been successfully applied in several previously reported studies, with the proviso that the visible onset of the event be sufficiently rapid. 11,13,14 In a comparative study of nucleation detection methods, it was shown for nucleation of paracetamol in a stirred crystallizer that the accuracy of using the naked eye is quite comparable to that obtained by FBRM and FTIR spectroscopy. 15 For the experiments with butyl paraben in ethanol, after nucleation was recorded in the three vessels, the circulation water was switched to the higher temperature, and the whole procedure repeated, for a total of up to 10 times for each solution.…”

Section: Nucleation Experimentsmentioning

confidence: 91%

“…13,16,17 The agitation rate was changed in a random pattern between experiments. For the experiments with mHBA in 1-propanol, as soon as sufficient crystalline material had precipitated in a vessel (between 10-15 min after nucleation was observed), the contents were filtered (Munktell grade 00A filter paper) and dried in a ventilated fume hood.…”

Section: Nucleation Experimentsmentioning

confidence: 99%

Influence of Agitation on Primary Nucleation in Stirred Tank Crystallizers

Liu

Svärd

2015

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The influence of agitation on nucleation of butyl paraben and m-hydroxybenzoic acid polymorphs has been investigated through 330 cooling crystallization experiments. The induction time has been measured at different supersaturation and temperature in three parallel jacketed vessels equipped with different overhead stirring agitators. In each case, the nucleating polymorph of mhydroxybenzoic acid has been identified by infrared spectroscopy. The influence of agitation rate, impeller type, impeller diameter, impeller to bottom clearance and the use of baffles have been investigated. A general trend in all the experiments is that the induction time decreases with increasing agitation rate. Across all experiments with different fluid mechanics for the butyl paraben system, the induction time is correlated to the average energy dissipation rate raised to the power -0.3. It is shown that this dependence is consistent with a turbulent flow enhanced cluster coalescence mechanism. In experiments with m-hydroxybenzoic acid, the metastable form II was always obtained at higher nucleation driving force while both polymorphs were obtained at lower driving force. In the latter case, form I was obtained in the majority of experiments at low agitation rate (100 rpm) while form II was obtained in all experiments at higher agitation rate (≥300 rpm).