Theophylline polymorphs by atomization of supercritical antisolvent induced suspensions

Miguel Ângelo Joaquim Rodrigues; Luís Miguel Borges Padrela; Vítor Manuel Geraldes Fernandes; José Santos; Henrique Aníbal Santos de Matos; Edmundo José Simões Gomes de Azevedo

Key information

Authors:

Miguel Ângelo Joaquim Rodrigues (Miguel Ângelo Joaquim Rodrigues); Luís Miguel Borges Padrela (Luís Miguel Borges Padrela); Vítor Manuel Geraldes Fernandes (Vítor Manuel Geraldes Fernandes); José Santos; Henrique Aníbal Santos de Matos (Henrique Aníbal Santos de Matos); Edmundo José Simões Gomes de Azevedo (Edmundo José Simões Gomes de Azevedo)

Published in

May 2011

Abstract

he Atomization of Supercritical Antisolvent Induced Suspensions (ASAIS) is a small volume supercritical antisolvent process characterized by the inline dissolution of the antisolvent before the liquid atomization for the solvent extraction step. The antisolvent (CO2) is mixed with the solute-containing solution in a small volume mixer immediately before the nozzle orifice in conditions such that cause the precipitation of the solutes. The generated suspension is then spray-dried for solvent separation. Compared to other similar particle-producing techniques, this approach allows a more efficient control of the antisolvent process and reduces the volume of the high-pressure precipitator by several orders of magnitude. Theophylline (TPL) particles produced by ASAIS are the polymorph previously obtained elsewhere by conventional SAS. Yet, the normal (non-polymorph) crystal form is obtained under non-antisolvent conditions. The required phase equilibria of the system TPL/tetrahydrofuran/CO2 between 308 K and 328 K were also obtained. The results presented here demonstrate that, under selected conditions, ASAIS is a continuous-regime alternative to conventional SAS for the production of unique products, such as crystal polymorphs.