Chiral resolution technology of is a crucial step in the pharmaceutical routes to ensure efficacy and save drug products. For chiral active pharmaceutical ingredients, the drug product formulation of a single enantiomer has been strongly recommended, since the racemates can represent an unnecessary burden on the body’s metabolism and allowing unwanted side effects. Due to cost-effectiveness, the crystallization of enantiopure forms of pharmaceutical has been the traditional and the most investigated method for enantiomer separation. To illustrate this problem, we will discuss the case of the Fluoxetine (FLX, Prozac®) which is a beta-blockers antidepressant drug belonging to the class of selective serotonin reuptake inhibitors used in the treatment of a variety of depression cases. The FLX is marketed as a racemic hydrochloride salt. However, in these cases both enantiomers have similar potency in terms of 5-HT inhibition. Normally when a racemate is aggregated from achiral process, a racemic equimolar arrangement of centrosymmetric enantiomers is formed. This is the case, for example of the FLX hydrochloride salt. Alternatively, the spontaneous resolution of racemic mixture could produce non-centrosimetric structures composed of two independent enantiomers in the asymmetric unit, which is a very rare event1.  

References:

1. Jacques, J.; Collet, A.; Wilen, S.H. Enantiomers, Racemates and Resolutions KriegerPub. Co., Malaber, FL, 1994.
2. Carvalho Jr., P.S.; Ellena, J.; Yufit, D.S.; Howard, J.A.K.Cryst. Growth & Des. 2016, 16, 3875-3883