Acta Pharm. 49 (1999) 291-298

Original scientific paper  

Hydrotropic and cosolvent solubilisation of indomethacin


Department of Pharmaceutics, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt 
Received March 18, 1999      Accepted July 28, 1999

The effect of four cosolvents, namely, ethanol, glycerol, propylene glycol (PG), and polyethylene glycol 400 (PEG 400) and two hydrotropic salts (sodium benzoate and sodium salicylate) on the aqueous solubility of indomethacin has been examined at two temperature levels (25 and 37 oC). The cosolvents used increased the solubility of the drug according to the following rank: PEG 400 > ethanol > PG > glycerol. Thermodynamic parameters were calculated and showed spontaneity of the solubility process (negative free energy change). Entropy and enthalpy changes were positive suggesting high degree of randomness of the system and an endothermic dissolution process. Both hydrotropes increased the aqueous solubility of indomethacin. Sodium benzoate exhibited greater effect compared to sodium salicylate. Solubilisation of indomethacin by hydrotropic salts is found not to be entirely pH-dependent. Electron density on the planar part of the substrate molecules determines the extent of solubilisation by a specific hydrotropic agent. The results obtained in this study might be of great use in the design of parenteral, topical and liquid formulations of the drug.

Keywords: indomethacin, solubilisation, cosolvents, hydrotropic salts, thermodynamic parameters