Solid-state characterization and dissolution properties of naproxen-arginine-hydroxypropyl-beta-cyclodextrin ternary system.
The effect of ternary complexation of naproxen, a poorly water soluble anti-inflammatory drug, with hydroxypropyl-beta-cyclodextrin and the basic aminoacid L-arginine on the drug dissolution properties has been investigated. Equimolar binary (drug-cyclodextrin or drug-arginine) and ternary (drug-cyclodextrin-arginine) systems were prepared by blending, cogrinding, coevaporation, and characterized by differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy, X-ray diffractometry. The dissolution behavior of naproxen from the different products was evaluated by means of a continuous flow through method. The results of solid state studies indicated the presence of strong interactions between the components in ternary coevaporated and coground systems, which were both of totally amorphous nature. In contrast, the presence of either free drug or free arginine was detected when the third component (cyclodextrin or aminoacid) was physically mixed, respectively, to the drug-arginine binary system (as physical mixture, coevaporate, or coground product) or to the drug-cyclodextrin binary system (as physical mixture, coevaporate, or coground product). All ternary combinations were significantly (P<0.001) more effective than the corresponding binary drug-cyclodextrin and drug-arginine systems in improving the naproxen dissolution rate. The best performance in this respect was given by the ternary coevaporate, with about 15 times increase in terms of both drug relative dissolution rate and dissolution efficiency. The synergistic effect of the simultaneous use of arginine and cyclodextrin on the dissolution rate of naproxen was attributed to the combined effects of inclusion in cyclodextrin and salt formation, as well as to a specific role played by arginine in this interaction.
Mura
Paola
P
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Firenze, Italy. mura@unifi.it
Bettinetti
Gian Piero
GP
Cirri
Marzia
M
Maestrelli
Francesca
F
Sorrenti
Milena
M
Catenacci
Laura
L
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001120:Arginine / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D009288:Naproxen / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility / Q000187:drug effects; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics
D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D009288:Naproxen; D001120:Arginine