title: Hot stage extrusion of p-amino salicylic acid with EC using CO2 as a temporary plasticizer.
abstract: 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.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium. gverreck@prdbe.jnj.com
authors.forename: Geert
authors.initials: G
authors.lastname: Verreck
authors.forename: Annelies
authors.initials: A
authors.lastname: Decorte
authors.forename: Koen
authors.initials: K
authors.lastname: Heymans
authors.forename: Jef
authors.initials: J
authors.lastname: Adriaensen
authors.forename: Dehua
authors.initials: D
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Tomasko
authors.forename: Albertina
authors.initials: A
authors.lastname: Arien
authors.forename: Jef
authors.initials: J
authors.lastname: Peeters
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Brewster
mesh_terms: 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
chemical_list: D010968:Plasticizers; D002245:Carbon Dioxide; D010131:Aminosalicylic Acid; C013517:ethyl cellulose; D002482:Cellulose