Cocrystals of Pentoxifylline: In Silico and Experimental Screening

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.