1261 ISSN 0326-2383 KEY WORDS: Biorelevant media, ibuprofen, phosphatidylcholine, sodium taurocholate, solubilization thermody- namics. * Author to whom correspondence should be addressed. E-mail: fmartinezr@unal.edu.co Latin American Journal of Pharmacy (formerly Acta Farmacéutica Bonaerense) Lat. Am. J. Pharm. 31 (9): 1261-9 (2012) Regular Article Received: May 10, 2012 Revised version: October 9, 2012 Accepted: October 11, 2012 Physicochemical Aspects of the Solubilization of Ibuprofen in Biorelevant Media: Modified and Classical FaSSIF Systems Sandra M. GÓMEZ, Diana M. CRISTANCHO & Fleming MARTÍNEZ* Grupo de Investigaciones Farmacéutico-Fisicoquímicas, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, A.A. 14490, Bogotá, D.C., Colombia. SUMMARY. In this work some thermodynamic information related to the transfer of ibuprofen (IBP) be- tween aqueous systems and micellar systems, in some biorelevant media, is reported. For this purpose, the apparent solubility of IBP at different temperatures, in the modified and classical Fasted State Simulated Intestinal Fluid (FaSSIF) biorelevant media, at different concentrations of sodium taurocholate and phos- phatidylcholine, was studied. It is observed that temperature and surfactant concentration affected the ap- parent solubility of this drug in these media. The solubility results were used to determine the micelle par- tition coefficients (K m/w ) in both media. For modified FaSSIF, K m/w values varied from 820 at 293.15 to 1471 at 313.15 K, whereas for classical FaSSIF, this property varied from 1147 to 1861, considering the same temperatures. The temperature dependence of solubility and micelle partition coefficient allowed the calculation of the respective thermodynamic quantities of transfer of IBP from the aqueous media to the micellar pseudo-phases. Gibbs energies were negative, but enthalpies and entropies were positive, indicat- ing spontaneous transfer processes in both media, and driven by entropy. The results were interpreted in terms of solute-micellar interactions, especially hydrogen bonding and electrostatics interactions. Also, the critical micelle concentrations (CMC) of surfactants in each medium were determined, obtaining values near to 8.0 and 4.0 mmol/L, for modified and classical FaSSIF, respectively. INTRODUCTION Ibuprofen (IBP, Fig. 1) is a non-steroidal an- ti-inflammatory drug (NSAID) derived of propi- onic acid used widely as analgesic and an- tipyretic, although it is also used for relief of symptoms of rheumatoid arthritis and os- teoarthritis, in addition to the treatment of dys- menorrheal, among other relevant indications. Like other NSAIDs its mechanism of action like- ly relates the inhibition of prostaglandin synthe- sis 1,2 . Although IBP is used widely nowadays in therapeutics, the physicochemical information about properties such as real and apparent solu- bility in aqueous media it is still not abundant for this drug. Solubility is an important factor affecting the intestinal absorption of drugs, because only the dissolved compounds can permeate the respec- tive membranes in order to reach the general circulation 3 . In particular, this property is criti- cal in the case of slightly soluble compounds. For this reason, the study of drugs solubility is relevant not only in aqueous media but also in the so-called biorelevant media, which have similar values of pH to the ones found in stom- ach and bowel; moreover, they have some com- pounds that act as biological surfactants, such as bile salts and phospholipids, as well 3 . Biorele- vant media were initially developed to improve the evaluation of the in vitro dissolution charac- Figure 1. Molecular structure of ibuprofen.