3 research outputs found
Demonstrating the Influence of Solvent Choice and Crystallization Conditions on Phenacetin Crystal Habit and Particle Size Distribution
Phenacetin was used as a model pharmaceutical
compound to investigate
the impact of solvent choice and crystallization conditions on the
crystal habit and size distribution of the final crystallized product.
The crystal habit of phenacetin was explored using crash-cooling crystallization
(kinetically controlled) and slow evaporative crystallization (thermodynamically
controlled) in a wide range of organic solvents. In general, a variety
of needle-type shapes (needles, rods, or blades) were recovered from
fast-cooling crystallizations, in contrast to hexagonal blocks obtained
from slow evaporative crystallizations. The solubility of phenacetin
was measured in five solvents from 10–70 °C to allow for
the design of larger-scale crystallization experiments. Supersaturation
and the nucleation temperature were independently controlled in isothermal
desupersaturation experiments to investigate the impact of each on
crystal habit and size. The crystal size (needle cross-sectional area)
decreased with increasing supersaturation because of higher nucleation
rates at higher supersaturation, and elongated needles were recovered.
Increasing the nucleation temperature resulted in the production of
larger crystals with decreased needle aspect ratios. Antisolvent phenacetin
crystallizations were developed for three solvent/antisolvent systems
using four different antisolvent addition rates to simultaneously
probe the crystal habit and size of the final product. In general,
increasing the antisolvent addition rate, associated with increased
rate of generation of supersaturation, resulted in the production
of shorter needle crystals
Utilizing Sulfoxide···Iodine Halogen Bonding for Cocrystallization
The propensity of a range of different sulfoxides and
sulfones
to cocrystallize with either 1,2- or 1,4-diiodotetrafluorobenzene,
via I···O=S
halogen bonding, was investigated. Cocrystallization occurred exclusively
with 1,4-diiodotetrafluorobenzene in either a 1:1 or 1:2 stoichiometry
of the organohalide and the sulfoxide, respectively, depending on
the sulfoxide used. It was found that the stoichiometry observed was
not necessarily related to whether the oxygen acts as a single halogen
bond acceptor or if it is bifurcated; with I···π
interactions observed in two of the cocrystals synthesized. Only those
cocrystals with a 1:2 stoichiometry exhibit C–H···O
hydrogen bonding in addition to I···O=S halogen bonding.
Examination of the Cambridge Structural Database shows that (i) the
I···O=S interaction is similar to other I···O
interactions, and (ii) the I···π interaction
is significant, with the distances in the two cocrystals among the
shortest known
Utilizing Sulfoxide···Iodine Halogen Bonding for Cocrystallization
The propensity of a range of different sulfoxides and
sulfones
to cocrystallize with either 1,2- or 1,4-diiodotetrafluorobenzene,
via I···O=S
halogen bonding, was investigated. Cocrystallization occurred exclusively
with 1,4-diiodotetrafluorobenzene in either a 1:1 or 1:2 stoichiometry
of the organohalide and the sulfoxide, respectively, depending on
the sulfoxide used. It was found that the stoichiometry observed was
not necessarily related to whether the oxygen acts as a single halogen
bond acceptor or if it is bifurcated; with I···π
interactions observed in two of the cocrystals synthesized. Only those
cocrystals with a 1:2 stoichiometry exhibit C–H···O
hydrogen bonding in addition to I···O=S halogen bonding.
Examination of the Cambridge Structural Database shows that (i) the
I···O=S interaction is similar to other I···O
interactions, and (ii) the I···π interaction
is significant, with the distances in the two cocrystals among the
shortest known