Assessment of solid-state interactions of naproxen with amorphous cyclodextrin derivatives by DSC

J Pharm Biomed Anal. 2002 Nov 7;30(4):1173-9. doi: 10.1016/s0731-7085(02)00421-1.

Abstract

A microcalorimetric method based on differential scanning calorimetry (DSC) of drug-additive binary systems to assess kneading-induced interactions was applied to naproxen (NAP) in combinations with amorphous hydroxypropyl beta-cyclodextrin (HPbetaCd), beta-cyclodextrin sulfobutyl ether, sodium salt ((SBE)(7m)-betaCd), acetyl beta-cyclodextrin (AcbetaCd) and acetyl gamma-cyclodextrin (AcgammaCd). Modifications of thermal parameters of NAP in DSC curves of physical mixtures indicate heating-induced interactions which resulted in a broadening of the NAP melting endotherm in the combinations with HPbetaCd, AcbetaCd and AcgammaCd. The effect of kneading on the interaction was particularly pronounced for the NAP-HPbetaCd and NAP-(SBE)(7m)-betaCd systems, which show a similar drug-to-carrier interaction ratio (1:2 by weight) as that of the other systems. Drug-to-carrier ratios, calculated considering the amount of NAP which recrystallizes from the melted mixtures equivalent to NAP not bound to the carrier, show a distinctly lower affinity in solid-state of the drug for the anionically charged (SBE)(7m)-betaCd with respect to other neutral carriers. The similar affinity of NAP for AcbetaCd and AcgammaCd demonstrates that the geometry of the cavity, which is a determinant factor for the inclusion complexation in liquid state, does not influence the interaction process in solid-state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning / methods
  • Chemistry, Pharmaceutical
  • Cyclodextrins / analysis*
  • Cyclodextrins / chemistry
  • Cyclodextrins / pharmacokinetics
  • Drug Carriers
  • Naproxen / analysis*
  • Naproxen / pharmacokinetics

Substances

  • Cyclodextrins
  • Drug Carriers
  • Naproxen