Role of Heteronucleants in Melt Crystallization of Crystalline Solid Dispersions.

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.

Solvent-Mediated Polymorphic Transformations in Molten Polymers: The Account of Acetaminophen.

Solvent-mediated polymorphic transformations (SMPTs) employing nonconventional solvents (polymer melts) is an underexplored research topic that limits the application of polymer-based formulation processes. Acetaminophen (ACM), a widely studied active pharmaceutical ingredient (API), is known to present SMPTs spontaneously (<30 s) in conventional solvents such as ethanol. Raman spectroscopy was employed to monitor the induction time for the SMPT of ACM II to I in polyethylene glycol (PEG) melts of different molecular weights (, 4000, 10 000, 20 000, 35 000 g/mol).

Polymorphism in Solid Dispersions.

Solid dispersions embed active pharmaceutical ingredients in polymeric carriers to improve their solubility. Three solid dispersion preparation techniques are typically employed: solvent evaporation, solvent-fusion, and fusion methods. Although these are also widely recommended as preparative methods for phase diagram determination, few examples exist concerning their effect on the resulting polymorph, once the solid dispersion is produced.

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes.

The inadvertent occurrence of polymorphic phase transformations in active pharmaceutical ingredients (APIs) during hot melt extrusion (HME) processes has been claimed to limit the application of this technique. Hence, the control of polymorphism would need to be addressed if there is any prospect of HME to be successfully implemented as an alternative solid dosage formulation strategy in integrated, continuous end-to-end pharmaceutical manufacturing settings. This work demonstrates that flufenamic acid (FFA), one of the most polymorphic APIs known, thus far, can be processed using temperature-simulated HME with polyethylene glycol (PEG) as polymeric carrier.