STEREOCHEMICAL ASPECTS OF THE MOLECULAR PHARMACEUTICS OF IBUPROFEN

Thermal analysis, thermodynamics of solution and molecular modelling o f (+)-ibuprofen and (+/-)-ibuprofen gave information on how heterochir al or homochiral interactions would affect the processing of ibuprofen . The study confirmed that (+/-)-ibuprofen exists as a true racemate w ith a 10% eutectic pure enantiomer composition. Both the racemate and the (+)-isomer crystal unit cells include four molecules and crystalli ze in the P2(1/c) and P2(1) space groups, respectively. Thus the inter molecular forces were different in each crystal. As a consequence the (+)-enantiomer lattice was more fragile but only slightly more soluble than the racemate in aqueous media. The solid-state structure contrib utions to solubility were different for the two crystals (DELTAH(+) = 51.1 and DELTAH(+/-) = 32.2 kJ mol-1) but the standard free energies o f the solutions were comparable for both compounds.