Sfe526_the micronization of drug particles by the rapid expansion of a supercritical solution_

The Micronization of Drug
Equipment
Applied Separations’ Helix Supercritical Particles by the Rapid
Expansion of a Supercritical
Solution
Introduction
A common problem in the pharmaceutical industry is that many drugs demonstrate poor solubility in water. Drugs that exhibit slow dissolution rates are less effective because they cannot quickly absorb Typically, the pharmaceutical industry uses micronization techniques to increase the Pack the dissolving vessel with the drug compound dissolution rates of drugs into biological fluids. and install vessel on the Helix. Dissolve the drug recrystallization of the solute particles from vessel to discharge the supercritical solution solutions using liquid antisolvents, along with through a nozzle into the crystallizer vessel. labor intensive techniques like crushing, milling, grinding, freeze drying, and spray-drying. Problems with traditional methods include the use Helix Conditions
of large amounts of solvent, solvent residues, The following RESS conditions were used in the broad particle size distributions, as well as thermal Dissolving Vessel
The rapid expansion of supercritical solutions (RESS) is an alternative technique for the micronization of particles using supercritical CO to quickly and naturally reduce the particle sizes of various drugs. Micronization by RESS involves dissolving a drug compound in a supercritical fluid, and then reducing the pressure across an expansion devise. The rapid depressurization of the Crystallizer Vessel
supercritical phase causes decreased solubility of the solute, and precipitation of the solute as a powder in a gas phase. The result of the process is the formation of fine particles with a narrow size distribution without the use of solvents or
Analysis
Scanning electron microscopy
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Results
Pharmaceutical Examples using RESS/CO2
Compound Particle Size (microns)
Aspirin

Conclusion
RESS produced ibuprofen particles with a median
size of 2.5 micron and a narrow particle
distribution. Micronization of drug compounds by
RESS using CO2 as a supercritical solvent can
significantly increase the rate of dissolution of
drug particles. RESS is a viable alternative to
conventional methods of micronization, providing
comparable results in the reduction of particle size
and degree of crystallinity without the problems
associated with mechanical grinding and solvent-
based procedures.
References
Charoenchaitrakool, M.; Dehghani, F.;
Foster, N.R; and Chan, H.K. “Mircronization by
Rapid Expansion of Supercritical Solutions to
Enhance the Dissolution Rates of Poorly Water-
Soluble Pharmaceuticals.” Ind. Eng. Chem. Res.
2000, 39, 4794-4802.
Subramamaniam, B.; Rajewski, R.; Snavely, K.;
“Pharmaceutical Processing with Supercritical
Carbon Dioxide.” J. Pharm. Sci. 1997, 86 (8), 885-
890.
Tom, J.W.; Debenedetti, P.G. “Particle Formation
with Supercritical Fluids—A Review.” J. Aerosol
Sci. 1991, 22 (5), 555-584.
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