Self-built supercritical CO2 anti-solvent unit design, construction and operation using Carbamazepine

Meng, Dan, Falconer, James, Krauel-Goellner, Karen, Chen, John J. J. J., Farid, Mohammed and Alany, Raid G. (2008) Self-built supercritical CO2 anti-solvent unit design, construction and operation using Carbamazepine. AAPS PharmSciTech, 9 3: 944-952. doi:10.1208/s12249-008-9130-0


Author Meng, Dan
Falconer, James
Krauel-Goellner, Karen
Chen, John J. J. J.
Farid, Mohammed
Alany, Raid G.
Title Self-built supercritical CO2 anti-solvent unit design, construction and operation using Carbamazepine
Formatted title
Self-built supercritical CO2 anti-solvent unit design, construction and operation using Carbamazepine
Journal name AAPS PharmSciTech   Check publisher's open access policy
ISSN 1530-9932
Publication date 2008-09
Sub-type Article (original research)
DOI 10.1208/s12249-008-9130-0
Open Access Status Not Open Access
Volume 9
Issue 3
Start page 944
End page 952
Total pages 9
Place of publication New York, NY United States
Publisher Springer New York
Language eng
Formatted abstract
The purpose of this study was to design and build a supercritical CO2 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, CO2 flow rate of 7.5 mL/min, pressure of 4,200 psi, over 3,000 s and at 33°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 μm. Furthermore, the SAS CO2 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.
Keyword Anti-solvent
Carbamazepine
In vitro dissolution
Particle size reduction
Polymorphism
Solid-state
Supercritical CO2
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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Created: Mon, 14 Dec 2015, 12:34:14 EST by Anthony Yeates on behalf of School of Pharmacy