Polymorph control in batch seeded crystallizers. A case study with paracetamol

Abstract

We show that seeding is not always sufficient to control cystal polymorphism and illustrate how kinetic modeling can help controlling polymorphism.

Improving Nefiracetam Dissolution and Solubility Behavior Using a Cocrystallization Approach

“…NCA, NOA, and NZC are incongruent in EtOH leading to a final slurry of Nefiracetam, whereas a congruent dissolution is observed in MeCN. In the case of an incongruent system in EtOH, a “spring-parachute” [ 46 , 47 ] behavior ( Figure 7 a) is expected meaning that the concentration reaches a maximum (“apparent solubility” [ 48 , 49 ]) before dropping to the solubility of the drug form crystallizing out (here Nefiracetam FI). The final solubility of Nefiracetam might, however, still be different as solution interactions will occur.…”

Nucleation kinetics for primary, secondary and ultrasound-induced paracetamol crystallization

“…1293 kg/m 3 , and 1332 kg/m 3 for form I). 31,32 Using eq. 11 33 and a molar weight of 151.16 g/mol, a molecular volume of 1.86⋅10 -28 m 3 is obtained.…”

Impurity incorporation in solution crystallization: diagnosis, prevention, and control

“…In those situations, the pairing with Raman spectroscopy could aid the detection of the new solid phase. 13,14…”

“…[7][8][9] Those attributes can be controlled by adjusting crystallization conditions and the addition of in situ and post-crystallization mechanical processing steps. [10][11][12][13][14] However, in contrast with the literature on crystallization for the control of crystal size, habit, and form, the amount of work relative to crystallization as a purification process is relatively scarce.…”