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- 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)
-
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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