Enantiomeric resolution of albuterol sulfate by preferential crystallization

Abstract

Albuterol is a β 2-adrenoceptor agonist prescribed for the treatment of bronchial asthma; it exists as a racemate and its bronchodilator activity resides in the ( R)-isomer or levalbuterol. The aim of this study was to determine a methodology that would separate the enantiomers of albuterol by preferential crystallization after a conglomerate is identified within its derivatives. We found that albuterol sulfate behaves as a conglomerate showing the characteristic α x-value = 2 (mole fraction solubility ratio of racemate vs enantiomer), the V-shaped ternary phase diagram and the preferential crystallization by seeding with the pure enantiomer. On the basis of these characteristics, we separated the enantiomers by entrainment, and crystallizing out a saturated methanolic solution of albuterol sulfate at 15 °C.