Theophylline polymorphs by atomization of supercritical antisolvent induced suspensions

J. P. Santos, DQ Group Author

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

The 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 (CO(2)) 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/CO(2) 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.
Original languageEnglish
Pages (from-to)303-312
JournalJournal of Supercritical Fluids
Volume58
Issue number2
DOIs
Publication statusPublished - 1 Sep 2011

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