title: Carbon dioxide extraction of residual chloroform from biodegradable polymers.
abstract: Biodegradable polymeric devices for drug delivery and tissue engineering are often fabricated with the use of organic solvents and may still contain significant amounts of solvent (> 1 wt%) even after aggressive vacuum drying. This excess solvent can interfere with tissue response and the mechanical properties of the devices. The aim of this article is to demonstrate that liquid CO(2) extraction can be used to reduce residual solvent in dense poly(L-lactide-co-glycolide) devices to 50 ppm relatively quickly and with minimal changes in architecture under some conditions. Two liquid CO(2) extraction systems were developed to examine the removal of residual solvents from bar-shaped PLGA devices: (1) a low-pressure (1400 psi) batch system, and (2) a high-pressure (5000 psi) continuous-flow system. Eight hours of extraction in the high-pressure system reduced residual chloroform in 3 mm thick bars below the 50-ppm target. A simple Fickian diffusion model was fit to the extraction results. Diffusion coefficients ranged from 1.10 x 10(-6) cm(2)/s to 2.64 x 10(-6) cm(2)/s. The model predicts that approximately 1 h is needed to dry 1-mm bars to chloroform levels below 50 ppm, and 7 h are needed for 3 mm thick bars. The micro- and macroarchitectures of porous PLGA scaffolds created by particulate leaching were not significantly altered by CO(2) drying if the salt used to make the pores was not removed before drying.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Koegler
authors.forename: Carmen
authors.initials: C
authors.lastname: Patrick
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cima
authors.forename: Linda G
authors.initials: LG
authors.lastname: Griffith
mesh_terms: D020341:Absorbable Implants; D001672:Biocompatible Materials / Q000737:chemistry*; D002245:Carbon Dioxide / Q000737:chemistry*; D002725:Chloroform / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008433:Mathematics; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D012997:Solvents; D002245:Carbon Dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002725:Chloroform