Assessment of solid-state interactions of naproxen with amorphous cyclodextrin derivatives by DSC.
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.
Bettinetti
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GP
Dipartimento di Chimica Farmaceutica, Università di Pavia, Viale Taramelli 12, I-27100, Pavia, Italy. gpbettinetti@unipv.it
Sorrenti
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M
Rossi
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Ferrari
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Mura
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Faucci
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MT
D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D009288:Naproxen / Q000032:analysis* / Q000493:pharmacokinetics
D003505:Cyclodextrins; D004337:Drug Carriers; D009288:Naproxen