Hot stage extrusion of p-amino salicylic acid with EC using CO2 as a temporary plasticizer.
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 the thermally labile p-aminosalicylic acid (p-ASA) and ethylcellulose 20cps (EC 20cps) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer. The thermal stability of the p-ASA was investigated using DSC, TGA and HPLC. The compound decomposes completely upon melting. Below 110 degrees C and under atmospheric conditions, the compound is thermally stabile for 10min. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. Carbon dioxide acted as plasticizer for p-ASA/EC 20cps, reducing the processing temperature during the hot stage extrusion process. HPLC showed that without carbon dioxide injection, approximately 17% of p-ASA degraded, while less than 5% degraded with CO(2) injection. The experiments clearly showed that injecting pressurized carbon dioxide broadens the application of hot stage extrusion to thermally labile compounds in a one step process.
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
Liu
Dehua
D
Tomasko
David
D
Arien
Albertina
A
Peeters
Jef
J
Van den Mooter
Guy
G
Brewster
Marcus E
ME
D010131:Aminosalicylic Acid / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002245:Carbon Dioxide / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D006358:Hot Temperature; D010968:Plasticizers / Q000737:chemistry*; D013818:Thermogravimetry
D010968:Plasticizers; D002245:Carbon Dioxide; D010131:Aminosalicylic Acid; C013517:ethyl cellulose; D002482:Cellulose