title: Interaction of naproxen with noncrystalline acetyl beta- and acetyl gamma-cyclodextrins in the solid and liquid state.
abstract: Randomly acetylated, amorphous beta-cyclodextrin (AcbetaCd) and gamma-cyclodextrin (AcgammaCd), having an average substitution degree per anhydroglucose unit, respectively, of 1.1 and 0.95 (approximately 7.7 acetyl residues per macrocycle), were investigated for their interactions in the solid and liquid state with naproxen (NAP). Differential scanning calorimetry (DSC), supported by X-ray powder diffractometry (XRD), of NAP-AcbetaCd and NAP-AcgammaCd blends revealed an apparent decrease in drug crystallinity which was related to a heating-induced solid-state interaction between the drug and each carrier. A solubility of approximately 0.40 NAP mass fraction in amorphous AcbetaCd and amorphous AcgammaCd at room temperature was determined. Phase-solubility analysis at 25, 37, and 45 degrees C accounted for A(L)-type inclusion complexation of NAP with AcbetaCd (K(1:1,25 degrees C)=4.5(4) x 10(3) l mol(-1)) and AcgammaCd (K(1:1,25 degrees C)=0.80(7) x 10(3) l mol(-1)) and revealed a solubilizing efficiency of AcbetaCd toward NAP approximately 4 times that of AcgammaCd. Equimolar drug-carrier combinations prepared from the respective blends by grinding, kneading, coevaporation and freeze-drying were characterized by DSC and XRD and tested for dissolution rate of NAP using the dispersed amount and continuous flow through methods. The best performance in terms of dissolution rate enhancement (approximately 23 times and approximately 10 times the dissolution efficiency of pure drug in the dispersed amount and continuous flow through tests, respectively) was displayed by the NAP-AcbetaCd colyophilized product.
authors.affiliation: Dipartimento di Chimica Farmaceutica, Università di Pavia, Viale Taramelli 12, I-27100 Pavia, Italy.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Bettinetti
authors.forename: Paola
authors.initials: P
authors.lastname: Mura
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Faucci
authors.forename: Milena
authors.initials: M
authors.lastname: Sorrenti
authors.forename: Massimo
authors.initials: M
authors.lastname: Setti
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003505:Cyclodextrins / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D011208:Powders; D012995:Solubility; D012996:Solutions; D013607:Tablets; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D011208:Powders; D012996:Solutions; D013607:Tablets; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D009288:Naproxen; C031215:betadex; C032613:alpha-cyclodextrin