(429a) A Theoretical-Experimental Analysis of the Precipitation of Acetaminophen and Tretinoin By Using Supercritical Enhanced Dispersion of Supercritical Fluids (SEDS)

Over the last decades, supercritical fluids (SCFs) technologies have been investigated as environmentally friendly techniques for pharmaceutical particle engineering. In this context, SCFs can be mainly used as solvents or antisolvents with the aim of micronizing drugs.

Solution enhanced dispersion by supercritical fluids (SEDS) is a SCF antisolvent technique in which the solution is atomized in a supercritical atmosphere (in this case supercritical CO₂). If the solid is poorly soluble in the SCF, and at the same time the SCF is highly soluble in the solvent, a great degree of supersaturation is achieved and an antisolvent effect is produced. Therefore, the solid precipitates in a reduced size without non-solvent traces. The main innovation of the SEDS process in relation with other SCFs technologies is the nozzle design. In this case, a coaxial nozzle with a mixing length is used in order to provide a previous mixture of the SCF and the solution, enhancing the mass transfer.

Thermodynamics, hydrodynamic, mass transfer and crystallization kinetics are therefore involved in that technique and they should be studied to get a complete understanding of the precipitation process.

A theoretical-experimental study of the precipitation of acetaminophen and tretinoin with SEDS has been performed in this work. Phase equilibria of the systems, atomization regimes and mass transfer coefficients of liquid and vapor phases have been separately studied.

According to the experimental results, the smallest particles without aggregates for both systems have been obtained at experimental conditions just above the mixture critical point of the antisolvent-solvent system with a high antisolvent-solvent mass flow rate ratio. On the other hand, according to the theoretical results, a high degree of supersaturation and a high mass transfer coefficient of the liquid phase are produced at these conditions. That means a great antisolvent effect because of the low liquid side mass transfer resistance and a small particle size because of the high supersaturation. Moreover, results indicate that a small initial droplet size provides a higher antisolvent effect.