Supercritical-fluid technology, a more established method than PRINT, may soon be used to manufacture an FDA-approved drug.
MAP Pharmaceuticals has been producing Levadex, its orally inhaled migraine therapy, through supercritical-fluid crystallization.
The company completed clinical development for the drug last year and will submit a New Drug Application during the first
half of 2011, according to the Form 10-K filed on Mar. 4, 2011.
Supercritical-fluid technology has been around for more than a century, and it is a common method for making decaffeinated
coffee. In the mid 1990s, the pharmaceutical industry began examining the technique as a way of manufacturing drug particles.
Because the process is rapid, and because no solvent is present during crystallization, drugmakers thought that supercritical-fluid
technology could yield uniform particles.
Supercritical fluids could be considered a fourth state of matter that combines the properties of liquids and gases. These
fluids can act as solvents or antisolvents. Carbon dioxide becomes a supercritical fluid when it is heated above 31.1 °C and
held at a pressure higher than 73.8 bar. Because of these characteristics, carbon dioxide has become the most common supercritical
fluid in the pharmaceutical industry.
Supercritical antisolvent precipitation (SAS) is one way to produce inhalable drug particles. In this method, a solution of
drug and organic solvent (e.g., budesonide in ethanol) is introduced into a flow of supercritical carbon dioxide, which extracts
the solvent rapidly from the drug solution. The drug substance then becomes supersaturated and forms particles in milliseconds.
Variations in SAS processes are distinguished by the ways in which the drug solution and supercritical fluid interact. Some
SAS processes are more efficient than others, but each of them yields dry powders in a single step.
Because carbon dioxide's critical temperature is not much different from ambient conditions, SAS is an attractive method for
processing pharmaceuticals, says Peter York, chief scientist at CrystecPharma and emeritus professor of physical pharmaceutics at the University of Bradford, United Kingdom. The process yields dry powders without
additives or residual solvents that might be unacceptable to regulators.