Effects of grinding with microcrystalline cellulose and cyclodextrins on the ketoprofen physicochemical properties.
Ground mixtures of ketoprofen (KETO) with native crystalline beta-cyclodextrin, amorphous statistically substituted methyl-beta-cyclodextrin, and microcrystalline cellulose were investigated for both solid phase characterization (differential scanning calorimetry (DSC) powder X-ray diffractometry, and infrared (IR) spectrometry) and dissolution properties (dispersed amount and rotating disk methods) to evaluate the role of the carrier on the performance of the final product. The effects of different grinding conditions, partial sample dehydration, and 1 year storage at room temperature were also investigated. The results pointed out the importance of the carrier nature on the efficiency of the cogrinding process. Both cyclodextrins were much more effective than was microcrystalline cellulose, even though no true inclusion complex formation occurred by mechanochemical activation. The best results were obtained from ground mixtures with methyl-beta-cyclodextrin, which showed the best amorphizing and solubilizing power toward the drug and permitted an increase of approximately 100 times its intrinsic dissolution rate constant, in comparison with the approximate 10 times increase obtained from ground mixtures with beta-cyclodextrin.
Dipartimento di Scienze Farmaceutiche, Firenze, Italy. mura@farmfi.scifarm.unifi.it
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002482:Cellulose; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins; D004055:Differential Thermal Analysis; D007660:Ketoprofen / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013997:Time Factors; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D002482:Cellulose; D007660:Ketoprofen; C109691:microcrystalline cellulose