Cocrystalization and simultaneous agglomeration using hot melt extrusion.
OBJECTIVE
To explore hot melt extrusion (HME) as a scalable, solvent-free, continuous technology to design cocrystals in agglomerated form.


METHODS
Cocrystal agglomerates of ibuprofen and nicotinamide in 1:1 ratio were produced using HME at different barrel temperature profiles, screw speeds, and screw configurations. Product was characterized for crystallinity by XRPD and DSC, while the morphology was determined by SEM. Dissolution rate and tabletting properties were compared with ibuprofen.


RESULTS
Process parameters significantly affected the extent of cocrystallization which improved with temperature, applied shear and residence time. Processing above eutectic point was required for cocrystallization to occur, and it improved with mixing intensity by changing screw configuration. Product was in the form of spherical agglomerates, which showed directly compressible nature with enhanced dissolution rate compared to ibuprofen. This marks an important advantage over the conventional techniques, as it negates the need for further size modification steps.


CONCLUSIONS
A single-step, scalable, solvent-free, continuous cocrystallization and agglomeration technology was developed using HME, offering flexibility for tailoring the cocrystal purity. HME being an established technology readily addresses the regulatory demand of quality by design (QbD) and process analytical technology (PAT), offering high potential for pharmaceuticals.
Dhumal
Ravindra S
RS
Centre for Pharmaceutical Engineering Science and Institute of Pharmaceutical Innovation, University of Bradford, Richmond Road, Bradford, UK.
Kelly
Adrian L
AL
York
Peter
P
Coates
Phil D
PD
Paradkar
Anant
A
D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D006358:Hot Temperature; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D014961:X-Ray Diffraction
D004364:Pharmaceutical Preparations