Ibuprofen, enantiomeric composition

Since the separated enantiomers of a dissymmetric compound must crystallize in a different space group than does the racemic mixture, it should not be unanticipated that quantitative XRPD would be useful in the determination of enantiomeric composition. For instance, the differing XRPD characteristics of (S)-(+)-ibuprofen relative to the (-RS)-racemate have been exploited to develop a sound method for the determination of the enantiomeric purity of ibuprofen samples [53]. 

Mustillo and CiurczakP" presented a paper discussing the spectral effect of optically active solvents on enantiomer mixes. This information was used as a technique to screen for polar modifiers in normal-phase chromatography of racemic mixtures. In 2000, the enantiomeric composition of ibuprofen in solid-state mixtures was performed by Agatonovic-Kurstrin, Beresford, Razzak. ... 

It is well known that resolved enantiomers and the racemic mixtures of dissymmetric substances ordinarily crystallize in different space groups,37 so it is natural to use quantitative XRPD as a means to determine the enantiomeric composition. This approach was demonstrated in the case of ibuprofen, taking advantage of the differing powder patterns of the resolved enantiomers and the racemate.38 The detection limits for either form (in the presence of the other form) were very similar, being approximately 3.3% w/w. 

Figure 3. Predicted enantiomeric composition versus actual composition for 60 mM of (A) ibuprofen (B) atenolol (C) phenylalanine and (D) alanine in S-CI ITA TI tN ionic liquid. Filled circles, S-enantiomers for ibuprofen and propranolol and L-enantiomers for phenylalanine and alanine Open circles, R-enantiomers for propranolol and D-enantiomers for phenylalanine and alanine.

Enantiomeric composition of ibuprofen was determined using a kinetic method based on the formation of trimeric complexes of this compound with chiral reference compounds (o-glucose, o-mannose, D-tartaric acid, D-galactose, and D-ribose) in electrosprayed solutions in the presence of divalent metal cations [32]. The described method can be applied to investigate interconversion of ibuprofen enantiomers under various conditions of the drug administration. This is of importance in view of ibuprofen standing in the pharmaceutical industry. 

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