Enhancement in Aqueous Solubility of Mefenamic Acid using Micellar Solutions of Various Surfactants

Abstract

The development of a meaningful dissolution procedure for drug products with limited water solubility has been a challenge to both the pharmaceutical industry and the agencies that regulate them. On the other hand, poorly soluble drugs present a big problem in pharmaceutical formulations. Therefore, various methods to improve the dissolution of poorly soluble drugs have been reported and employing surfactants for this purpose is the leading approach. In spite of wide applications of Mefenamic acid, the enhancement of its solubility in water using surfactant systems has not been explored. Therefore, we have investigated the interaction between this drug and anionic (SDS, SDBS, DTAB, CTAB, TTAB) surfactants as well as non-ionic (Tween 20, Tween 40, Tween 60, Tween 80, Brij 30, Brij 35,Brij 56 and Brij 58) surfactants. The results show that, irrespective of the surfactant type, the solubility of Mefenamic acid increases with increase in concentration of a surfactant, leading to the conclusion that there is an association between the drug and the surfactants. The molar solubilization ratio, micelle–water partition coefficient (K M), binding constant (K) and the Gibbs energy of solubilization ( $$ \Delta G_{\text{s}}^{\text{o}} $$ ) of the drug in the micelles were determined to yield a model to correlate the solubility with the structure of the surfactant used. An outcome of the results is that the order of solubility of this drug in non-ionic and ionic surfactants is Tween 80 > Tween 60 > Tween 40 > Tween 20 and, in the case of the Brij series, is Brij56 > Brij58 > Brij35 > Brij30, while in cationic and anionic surfactants the order is CTAB > TTAB > DTAB and SDBS > SDS.