Characterisation of the interaction between fenamates and hydroxy-propyl-β-cyclodextrin

Written by Fülöp Ibolya, Gyéresi Árpád, Hobai Ştefan

Cyclodextrins are non-reducing cyclic oligosaccharides able to enclose drug molecules into their central lipophilic cavity. Forming complexes with cyclodextrins is used to solubility and bioavailability enhancement of drugs. The aim of our paper is the analysis of the mixtures containing mefenamic acid (MA), flufenamic acid (FA) – poorly water-soluble non-steroidal anti-inflammatory drugs – and hydroxy-propyl-β-cyclodextrin (HP-β-CD). We prepared mixtures containing MA, FA and HP-β-CD in 1:1 and 1:2 molar ratios by kneading and co-precipitation methods. The mixtures were analysed by differential scanning calorimetry (DSC) and the stability constants were calculated from the phase solubility diagrams. Using DSC thermograms can be calculated the complexed drug amount that varies between 1 and 23% in the case of FA and 6-58% at the MA mixtures. The phase solubility studies indicate that complexes with 1:1 stoichiometric ratio are formed. The stability constants are 70 ± 3 M-1 for MA and 470 ± 5 M-1 for FA. In conclusion we can affirm that HP-β-CD increases the solubility of MA and FA. The results obtained by the DSC analysis show the formation of inclusion complexes.

 

Keywords: mefenamic acid, flufenamic acid, hydroxy-propyl-β-cyclodextrin, differential scanning calorimetry


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