title: Influence of solvent on crystal nucleation of risperidone.
abstract: Over 2100 induction time experiments were carried out for the medium-sized, antipsychotic drug molecule, risperidone in seven different organic solvents. To reach the same induction time the required driving force increases in the order: cumene, toluene, acetone, ethyl acetate, methanol, propanol, and butanol, which reasonably well correlates to the interfacial energies as determined within classical nucleation theory. FTIR spectroscopy has been used to investigate any shifts in the spectra and to estimate the interaction of solute and solvent at the corresponding site. The solution condition has also been investigated by Density Functional Theory (DFT) calculations over (1 : 1) solvent-solute binding interactions at 8 different sites on the risperidone molecule. The DFT computational results agree with the spectroscopic data suggesting that these methods do capture the binding strength of solvent molecules to the risperidone molecule. The difficulty of nucleation correlates reasonably to the DFT computations and the spectroscopic measurements. The results of the different measurements suggest that the stronger the solvent binds to the risperidone molecule in solution, the slower the nucleation becomes.
authors.affiliation: Materials and Surface Science Institute, Chemical and Environmental Science Department, University of Limerick, Limerick, Ireland. ake.rasmuson@ul.ie jacek.zeglinski@ul.ie.
authors.forename: Donal
authors.initials: D
authors.lastname: Mealey
authors.forename: Jacek
authors.initials: J
authors.lastname: Zeglinski
authors.forename: Dikshitkumar
authors.initials: D
authors.lastname: Khamar
authors.forename: Åke C
authors.initials: ÅC
authors.lastname: Rasmuson
mesh_terms: D000433:1-Propanol / Q000737:chemistry; D000085:Acetates / Q000737:chemistry; D000096:Acetone / Q000737:chemistry; D001555:Benzene Derivatives / Q000737:chemistry; D000440:Butanols / Q000737:chemistry; D003460:Crystallization; D000432:Methanol / Q000737:chemistry; D011789:Quantum Theory; D018967:Risperidone / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014050:Toluene / Q000737:chemistry
chemical_list: D000085:Acetates; D001555:Benzene Derivatives; D000440:Butanols; D012997:Solvents; D000096:Acetone; D014050:Toluene; C007650:ethyl acetate; C015763:cumene; D000433:1-Propanol; D018967:Risperidone; D000432:Methanol