Self-built supercritical CO2 anti-solvent unit design, construction and operation using carbamazepine.
The purpose of this study was to design and build a supercritical CO(2) anti-solvent (SAS) unit and use it to produce microparticles of the class II drug carbamazepine. The operation conditions of the constructed unit affected the carbamazepine yield. Optimal conditions were: organic solution flow rate of 0.15 mL/min, CO(2) flow rate of 7.5 mL/min, pressure of 4,200 psi, over 3,000 s and at 33 degrees C. The drug solid-state characteristics, morphology and size distribution were examined before and after processing using X-ray powder diffraction and differential scanning calorimetry, scanning electron microscopy and laser diffraction particle size analysis, respectively. The in vitro dissolution of the treated particles was investigated and compared to that of untreated particles. Results revealed a change in the crystalline structure of carbamazepine with different polymorphs co-existing under various operation conditions. Scanning electron micrographs showed a change in the crystalline habit from the prismatic into bundled whiskers, fibers and filaments. The volume weighted diameter was reduced from 209 to 29 mum. Furthermore, the SAS CO(2) process yielded particles with significantly improved in vitro dissolution. Further research is needed to optimize the operation conditions of the self-built unit to maximize the production yield and produce a uniform polymorphic form of carbamazepine.
Meng
Dan
D
Department of Chemical and Material Engineering, Faculty of Engineering, University of Auckland, Private Bag 92019, Auckland, New Zealand. d.meng@auckland.ac.nz
Falconer
James
J
Krauel-Goellner
Karen
K
Chen
John J J J
JJ
Farid
Mohammed
M
Alany
Raid G
RG
D002220:Carbamazepine / Q000032:analysis / Q000737:chemistry*; D002245:Carbon Dioxide / Q000032:analysis / Q000737:chemistry*; D025924:Chromatography, Supercritical Fluid / Q000295:instrumentation* / Q000379:methods; D012997:Solvents / Q000032:analysis / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000295:instrumentation / Q000379:methods
D012997:Solvents; D002245:Carbon Dioxide; D002220:Carbamazepine