The influence of polyvinylpyrrolidone on naproxen complexation with hydroxypropyl-β-cyclodextrin

The combined effect of hydroxypropyl-beta -cyclodextrin (HP beta CD) and polyvinplpyrrolidone (PVP) on the solubility of naproxen (NAP) was studied. Phase-solubility analysis at different temperatures was used to investigate interactions in aqueous solution between NAP and the carriers. either alone or in combination. Equimolar NAP-HP beta CD solid systems. in the presence or the absence of 15% (w/w) PVP, were prepared by cogrinding, kneading, coevaporation or freeze-drying, and characterized by differential scanning calorimetry, X-ray powder diffraction analysis, infrared spectroscopy and dissolution rates. The combined use of PVP and HP beta CD resulted in a synergistic increasing effect of the aqueous solubility of NAP (120 times that of the purr drug). The phenomenon was interpreted in terms of the strongest complexation capacity of HP beta CD towards NAP, which was reflected by an about 65% increase in the apparent stability constant of the NAP-HP beta CD complex in the presence of only 0.1% (w/v) PVP. Variations in thermodynamic parameters accounted for a PVP role in the formation of a NAP-HP beta CD-PVP ternary complex. The positive effect of PVP also reflected on NAP dissolution rates from solid preparations, because all ternary systems, with the exception of physical mixtures. dissolved faster than the corresponding NAP-HP beta CD binary systems. The results of solid state studies accounted for the occurrence of mechanically- and/or thermally-induced stronger interactions in ternary than in binary systems, that in some cases led to a complete loss of NAP crystallinity. (C) 2001 Elsevier Science B.V. All rights reserved.