The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.
The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.
Verreck
Geert
G
Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium. gverreck@prdbe.jnj.com
Decorte
Annelies
A
Heymans
Koen
K
Adriaensen
Jef
J
Cleeren
Dirk
D
Jacobs
Adri
A
Liu
Dehua
D
Tomasko
David
D
Arien
Albertina
A
Peeters
Jef
J
Rombaut
Patrick
P
Van den Mooter
Guy
G
Brewster
Marcus E
ME
D000179:Acrylates / Q000008:administration & dosage*; D002245:Carbon Dioxide / Q000008:administration & dosage*; D017964:Itraconazole / Q000008:administration & dosage*; D008853:Microscopy; D010968:Plasticizers / Q000008:administration & dosage*; D011759:Pyrrolidines; D011760:Pyrrolidinones / Q000008:administration & dosage*; D013678:Technology, Pharmaceutical; D013696:Temperature; D014753:Vinyl Compounds / Q000008:administration & dosage*
D000179:Acrylates; D010968:Plasticizers; D011759:Pyrrolidines; D011760:Pyrrolidinones; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D002245:Carbon Dioxide; D017964:Itraconazole