Role of Heteronucleants in Melt Crystallization of Crystalline Solid Dispersions

Abstract

Few publications exist concerning polymorphic control during melt crystallization, particularly when employing heteronucleants.Here, the influence of a polymeric thin film (polyethylene terephthalate, PET) on the crystallization from melt of the polymorphic compound acetaminophen (ACM) in polyethylene glycol (PEG) was investigated. Molten ACM−PEG at different compositions was monitored using in situ Raman spectroscopy for nucleation induction time measurements and phase identification. Furthermore, X-ray diffraction (XRD) served to analyze the preferred orientation (PO) of the pastilles (solidified melt droplets) on PETcoated and uncoated substrates. The results indicate that PET-coated substrates qualitatively accelerate the nucleation of ACM form II (ACM II) in PEG compared to uncoated glass substrates. Additionally, the occurrence of ACM II in PEG was increased by an average of 10% when crystallized on PET-coated substrates compared to uncoated substrates. Overall, these results suggest that ACM can interact through hydrogen bonding with the PET-coated substrate, leading to faster nucleation. This investigation illustrates the effect of PET-coated substrates in the selective crystallization of ACM II in PEG as crystalline solid dispersions (CSDs). Ultimately, the results suggest the implementation of polymeric heteronucleants in melt crystallization processes, specifically, in advanced polymerbased formulation processes for the enhanced polymorphic form control of pharmaceutical compounds in CSDs.

Real-Time Monitoring of Crystallization Processes Using a Novel Compact Composite Sensor Array

“…The acquisition parameters were optimized with the iC Raman software (Mettler-Toledo, v.4.1.917.0) to capture spectra in 1 min intervals with 10 accumulations and an exposure time of 2 s while employing automatic cosmic ray filter removal and intensity correction. The intensity for the Raman shifts at 1680 cm –1 (FFA solution concentration), 685 cm –1 (FFA I), and 615 cm –1 (FFA III) were monitored by calculating the peak height using a two-point baseline correction. , …”