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

• Published in: European journal of pharmaceutical sciences Vol. 13; no. 2; pp. 187 - 194
• Main Authors: Mura, Paola, Faucci, M.Teresa, Bettinetti, Gian Piero
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01-05-2001; Elsevier
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Anti-Inflammatory Agents, Non-Steroidal - chemistry; beta-Cyclodextrins; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Cyclodextrins - chemistry; differential scanning calorimetry; General pharmacology; Hydroxypropyl-β-cyclodextrin; Medical sciences; Naproxen; Naproxen - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyvinylpyrrolidone; Povidone - chemistry; Solubility; Solubilization; Temperature; Ternary complexes; X-ray powder diffraction analysis; X-ray powder diffraction analysis; Naproxen; differential scanning calorimetry; Hydroxypropyl-β-cyclodextrin; Polyvinylpyrrolidone; Solubilization; Ternary complexes; Non steroidal antiinflammatory agent; Complexation; Cyclodextrin; Pharmaceutical technology; Pyrrolidone(vinyl) polymer; Oligosaccharide; Dosage form; Arylpropionic acid derivatives; Inclusion compound; Dissolution
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(01)00093-8

The combined effect of hydroxypropyl-β-cyclodextrin (HPβCD) and polyvinylpyrrolidone (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–HPβCD 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 HPβCD resulted in a synergistic increasing effect of the aqueous solubility of NAP (120 times that of the pure drug). The phenomenon was interpreted in terms of the strongest complexation capacity of HPβCD towards NAP, which was reflected by an about 65% increase in the apparent stability constant of the NAP–HPβCD 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–HPβCD–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–HPβCD 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.