Influence of the preparation method on the physical-chemical properties of ketoprofen-cyclodextrin-phosphatidylcholine ternary systems.

摘要

The aim of this work was to assess the effectiveness and actual advantages of the microwave (MW) technology for preparing ternary complexes of ketoprofen (Keto) with beta-cyclodextrin (beta-Cd) or methylated-beta-cyclodextrin (Mebeta-Cd) and phosphatidylcholine (EPC3) with respect to conventional preparation methods, such as co-grinding and sealed-heating. The products obtained with the different techniques were characterized by differential scanning calorimetry (DSC), X-ray powder diffractometry, FT-IR spectroscopy and dissolution studies. For each method, the influence of different experimental conditions on the physical-chemical properties of the final products has been also investigated. DSC analysis was used to monitor physical stability of ternary complexes during 2 years storage under ambient conditions. MW irradiation resulted to be a rapid and very convenient preparation technique. In fact, it was more effective than the considered conventional methods, enabling obtainment in shorter times of products with better performance. In particular, the Keto-Mebeta-Cd-EPC3 product prepared by MW treatment at 750 W for 10 min allowed achievement of about 80% of drug dissolution after 60 min, in comparison with the 50% and 63% values obtained for the corresponding products prepared by 30-min co-grinding or 60-min sealed-heating. Moreover, such ternary products were more effective in improving drug dissolution than the corresponding Keto-Mebeta-Cd systems. Furthermore, the MW treatment at such irradiation energy enabled obtainment of totally dehydrated samples, which maintained unchanged solid-state characteristics and showed no susceptibility to ambient humidity after 2 years storage at ambient temperature. Therefore, MW-treated Keto-Mebeta-Cd-EPC3 systems can be successfully used for formulation of tablets with enhanced drug dissolution behaviour.