Effect of 2-hydroxypropyl-β-cyclodextrin on solubility of sparingly soluble drug derivatives of anthranilic acid

Int J Mol Sci. 2011;12(4):2383-94. doi: 10.3390/ijms12042383. Epub 2011 Apr 6.

Abstract

Guest-host complex formation of three drug derivatives of anthranilic acid, mefenamic acid, niflumic acid, and flufenamic acid with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD) in aqueous solutions was investigated using "Phase solubility study" with UV-vis spectrophotometry. Solubility of sparingly soluble drugs has been improved by addition of 2HP-β-CD at two temperatures 298.15 K and 310.15 K and two pH values 2 and 7. The influence of different 2HP-β-CD concentration on solubility of drugs at different pH and temperatures has been investigated. The 2HP-β-CD-drug complex stability constants (K(s)), and dissociations constants (K(d)), as well as the thermodynamic parameters of reaction, i.e., the free energy change (ΔG), the enthalpy change (ΔH) and the entropy change (ΔS), were determined. The experimental data indicated formation of 1:1 inclusion complexes, which were found effective binders increasing the solubility of drugs.

Keywords: 2-hydroxypropyl-β-cyclodextrin; experimental solubility; solubility enhancement; thermodynamics of complex formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Flufenamic Acid / chemistry
  • Mefenamic Acid / chemistry
  • Niflumic Acid / chemistry
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Temperature
  • Thermodynamics
  • beta-Cyclodextrins / chemistry*
  • ortho-Aminobenzoates / chemistry*

Substances

  • beta-Cyclodextrins
  • ortho-Aminobenzoates
  • anthranilic acid
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Mefenamic Acid
  • Niflumic Acid
  • Flufenamic Acid