Cocrystals of Pentoxifylline: In Silico and Experimental Screening

Crystal Growth Design 2015
Dmitrijs Stepanovs, Māra Jure, Liudmila N. Kuleshova, Detlef W. M. Hofmann, Anatolijs Mišņovs

To obtain new crystal forms with altered physicochemical properties and to get insight into the driving forces guiding cocrystallization, we performed experimental and in silico screening of pentoxifylline with 11 pharmaceutically acceptable organic acids. Neat grinding, liquid-assisted grinding, and slow solvent evaporation were used to obtain cocrystals of pentoxifylline. The free energy of experimental and hypothetical crystal structures have been calculated using the FlexCryst program. Three cocrystals of pentoxifylline with aspirin, salicylic acid, and benzoic acid in a 1:1 molar ratio have been obtained and characterized by physical methods. The experimental and in silico results were found to match very well. Strong correlation between melting points of pentoxifylline cocrystals and coformers has been detected. A significant decrease in solubility of pentoxifylline cocrystals as compared to pure pentoxifylline was observed.

Keywords
Pentoxifylline, aspirin, benzoic acid, salicylic acid, pharmaceutical cocrystals, single crystal X-ray crystallography, cocrystal screening in silico
DOI
10.1021/acs.cgd.5b00185
Hyperlink
http://pubs.acs.org/doi/abs/10.1021/acs.cgd.5b00185

Stepanovs, D., Jure, M., Kuleshova, L., Hofmann, D., Mišņovs, A. Cocrystals of Pentoxifylline: In Silico and Experimental Screening. Crystal Growth Design, 2015, Vol.15, Iss.8, pp.3652-3660. ISSN 1528-7483. e-ISSN 1528-7505. Available from: doi:10.1021/acs.cgd.5b00185

Publication language
English (en)