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3035418 
Journal Article 
Simultaneous formation and micronization of pharmaceutical cocrystals by rapid expansion of supercritical solutions (RESS) 
Müllers, KC; Paisana, M; Wahl, MA 
2015 
1 
Pharmaceutical Research
ISSN: 0724-8741
EISSN: 1573-904X 
32 
2 
702-713 
English 
25213775 
WOS:000349357700029 
PURPOSE: We investigated the RESS process as a means of simultaneous micronization and cocrystallization of a model drug with poor aqueous solubility.

METHODS: 1:1 cocrystals of ibuprofen (IBU) and nicotinamide (NA) were produced with a pilot scale unit for RESS processing.IBU and NA were dissolved in scCO2 at 30 MPa and 50°C. After 24 h, the supercritical solution was expanded at a medium CO2 flow rate of 3.8 kg/h during 60 min into an expansion vessel kept at ambient conditions. Cocrystals were identified with DSC, XRD and confocal Raman microscopy (CRM) and further characterized by SEM, specific surface area, wetting ability, solubility and dissolution testing.

RESULTS: Judging by DSC, XRD and CRM, cocrystals with high purity could be produced with the RESS technique. Micronization via RESS was successful, since the specific surface area of RESS cocrystals was increased almost tenfold in comparison to cocrystals produced by slow solvent evaporation. Due to the additional micronization, the mean dissolution time of IBU from RESS cocrystals was decreased.

CONCLUSIONS: RESS cocrystallization offers the advantage of combining micronization and cocrystallization in a single production step. For drugs with dissolution-limited bioavailability, RESS cocrystallization may therefore be a superior approach in comparison to established cocrystallization techniques. 
cocrystals; dissolution; ibuprofen; RESS; supercritical fluids