Physical-chemical characterization of binary and ternary systems of ketoprofen with cyclodextrins and phospholipids.
Binary and ternary interaction products of ketoprofen (an anti-inflammatory drug very poorly water soluble) with phospholipids (phosphatidylcholine (EPC3) and phosphatidylglycerol (EPG)) and cyclodextrins (beta-cyclodextrin and its methylated derivative (MebetaCd)), were prepared to evaluate their ability in improving drug dissolution properties. The different binary and ternary drug-carrier(s) systems were obtained by microwave irradiation, in order to investigate the effectiveness of such a newly proposed preparation technology in bringing about effective solid-state interactions among the components. The effect of different experimental conditions such as microwave irradiation power (500 and 750 W) and treatment time (5, 10 and 15 min) on the physicochemical properties of the products has been also assessed. All solid systems were characterized by differential scanning calorimetry (DSC) analysis, supported by X-ray powder diffractometry, and examined for dissolution properties. The study pointed out the better performance of ternary systems than the binary ones and allowed selection of the best drug-phospholipid-Cd combination and of the most effective preparation conditions. In particular drug-EPC3-MebetaCd ternary systems obtained by using the greatest microwave irradiation energy and the longest treatment time exhibited complete drug amorphization and allowed achievement after 60 min of almost 80% dissolved drug, with an increase in dissolution efficiency of 10.7 and 1.4 times in comparison with drug alone and the corresponding drug-Cd binary system, respectively. The synergistic effect between cyclodextrin and phospholipid in enhancing the drug dissolution properties has been attributed to the combination of the surfactant properties of phospholipids and the wetting and solubilizing power of cyclodextrins and/or the possible formation of a "multicomponent" complex.
Cirri
Marzia
M
Department of Pharmaceutical Sciences, University of Florence, via Schiff 6 Sesto Fiorentino, 50019 Florence, Italy.
Maestrelli
Francesca
F
Mennini
Natascia
N
Mura
Paola
P
D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000737:chemistry; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002627:Chemistry, Physical / Q000379:methods; D003505:Cyclodextrins / Q000032:analysis* / Q000737:chemistry; D007660:Ketoprofen / Q000032:analysis* / Q000737:chemistry; D008872:Microwaves; D010743:Phospholipids / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry
D000893:Anti-Inflammatory Agents; D003505:Cyclodextrins; D010743:Phospholipids; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D007660:Ketoprofen; C031215:betadex