An approach to solvent screening for crystallization of polymorphic pharmaceuticals and fine chemicals

Characterization and Selective Crystallization of Famotidine Polymorphs

“…48 Solvents with higher polarity index have more tendencies in disrupting hydrogen bonding between solute molecules. 49 The solvent properties may be described by solvent property parameters, including hydrogen bond acceptor propensity, hydrogen bond donor propensity, polarity/dipolarity, dipole moment, dielectric constant, viscosity, surface tension, and cohesive energy density, etc. Eight property parameters of three solvents used in this work are listed in Table 3.…”

Solid-State Characterization and Interconversion of Recrystallized Amodiaquine Dihydrochloride in Aliphatic Monohydric Alcohols

“…The mechanism of modification can be best explained by solvent-solute interactions (20,28). Hydrogen bond formation, between solvent and solute, plays a key role in the formation of different solid-state morphology (19,20,28). Normally, there are three types of solvents used in routine morphology screening.…”

“…Second, dipolar aprotic solvents which are polar but not hydrogen bond donor, such as acetonitrile. Finally, dipolar protic solvents which are polar with hydrogen bond donor, such as water, methanol, and ethanol (20). In this study, only dipolar protic solvents were chosen because aliphatic alcohols are commonly encountered in many pharmaceutical manufacturing processes.…”

“…In this study, only dipolar protic solvents were chosen because aliphatic alcohols are commonly encountered in many pharmaceutical manufacturing processes. These solvents exhibit hydrogen bond donor functional group that can interact with amodiaquine dihydrochloride via hydrogen bond formation, which is different than water, and caused morphology rearrangement of original AQ-DD to the resulting recrystallized form (20). Almandoz and coworkers (21) Consequently, the recrystallized crystals of amodiaquine dihydrochloride obtained from these three aliphatic alcohols showed the same solid state morphology but very different from the original AQ-DD raw material.…”

“…However, the above known solidstate morphologies of AQ in correlation with their physicochemical properties have not yet been reported. Therefore, the objective of this study is to evaluate the differences in amodiaquine dihydrochloride solid-state morphology after recrystallizing in various alcoholic solvents (18)(19)(20)(21) and correlate them with their respective physicochemical properties. Methanol, ethanol, and npropanol, which are monohydric alcohols, were selected as recrystallizing solvents due to their increasing series in carbon number and have not been used as pure form for AQ solidstate morphology screening in all previous reports.…”