Physicochemical evaluation of carbamazepine microparticles produced by the rapid expansion of supercritical solutions and by spray-drying.
OBJECTIVE
To compare the physical and physicochemical characteristics of carbamazepine microparticles prepared using two different methods: (1) the rapid expansion of supercritical solutions (RESS) and (2) the spray-drying process.


METHODS
For both processes, microparticles were produced over a range of different temperatures (35 to 100 degrees C). For the RESS method, carbon dioxide was the solvent used over a pressure range of 2500 to 3500 psi. As for the spray-drying method, different organic solvents were used at atmospheric pressure. Comparison was based on morphology, crystalline structure, mean particle size, and size distribution of processed particles. The influence of process parameters on microparticles' characteristics was also investigated. Particles were analyzed using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), thermogravimetric analyzer (TGA), and differential scanning calorimetry (DSC).


RESULTS
The carbamazepine particles used as unprocessed starting material had a mean diameter of approximately 85 microm with a size distribution range between 15 and 336 microm. Microparticles produced by either the RESS or spray-drying method had a mean diameter smaller than 2 microm and a narrower size distribution range between 0.25 and 2.5 microm. SEM photomicrographs, X-ray diffractograms, and DSC spectra revealed that modification of crystal morphology was dependent on the operating conditions.


CONCLUSIONS
Significant reduction in mean particle size and size distribution range of carbamazepine particles was observed by RESS and spray-drying methods. The results also demonstrate that the crystalline nature of carbamazepine particles depends on the method of production and on the operating parameters of pressure and temperature.
Gosselin
Patrick
P
Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada. patrick.gosselin@umontreal.ca
Lacasse
François-Xavier
FX
Preda
Michel
M
Thibert
Roch
R
Clas
Sophie-Dorothée
SD
McMullen
Jean Norbert
JN
D002220:Carbamazepine / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D025924:Chromatography, Supercritical Fluid / Q000295:instrumentation / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008863:Microspheres; D019999:Pharmaceutical Solutions / Q000138:chemical synthesis*
D019999:Pharmaceutical Solutions; D002220:Carbamazepine