Thermodynamic Study of Racemic Ibuprofen Separation by Liquid Chromatography Using Cellulose-Based Stationary Phase

Abstract

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), also known for its significant antipyretic and analgesic properties. This chiral drug is commercialized in racemic form; however, only S-(+)-ibuprofen has clinical activities. In this paper the effect of temperature change (from 288.15 to 308.15 K) on the ibuprofen resolution was studied. A column ( 250 × 4.6 mm) packed with tris(3,5-dimethylphenylcarbamate) was used to obtain the thermodynamic parameters, such as enthalpy change ( Δ H ), entropy change ( Δ S ), variation enthalpy change ( Δ Δ H ), variation entropy change ( Δ Δ S ), and isoenantioselective temperature ( T iso ). The mobile phase was a combination of hexane (99%), isopropyl alcohol (1%), and TFA (0.1%), as an additive. The conditions led to a selectivity of 1.20 and resolution of 4.55. The first peak, R-(−)-ibuprofen, presented an enthalpy change of 7.21 kJ/mol and entropy change of 42.88 kJ/K·mol; the last peak, S-(+)-ibuprofen, has an enthalpy change of 8.76 kJ/mol and 49.40 kJ/K·mol of entropy change.