Physicochemical characterization, in vitro dissolution behavior, and pharmacodynamic studies of rofecoxib-cyclodextrin inclusion compounds. Preparation and properties of rofecoxib hydroxypropyl β-cyclodextrin inclusion complex: A technical note

An inclusion complex of rofecoxib and HPβ-CD was prepared successfully by the spray-drying method in a molar ratio of 1∶1. The inclusion complex was found to have improved in vitro drug release compared with the pure drug. The solubility profile of complexes of rofecoxib prepared using HPβ-CD as the complexing agent in a molar ratio of 1∶1 by the spray-drying method in pH 1.2 and pH 7.4 indicated that the acid solubility of rofecoxib was enhanced considerably by formation of an inclusion complex with HPβ-CD. The above results also clearly demonstrated a significant decrease in the gastric ulcerogenic activity of rofecoxib through complexation with cyclodextrins. Even though the physical mixture of rofecoxib with cyclodextrins reduced ulcer formation, it was the spray-dried complex formation approach that minimized gastric ulceration. These findings are extremely important from a commercial point of view as the prepared complex removes a major drawback for rofecoxib in therapy

Diclofenac-β-cyclodextrin binary systems: Physicochemical characterization and in vitro dissolution and diffusion studies

The aim of this work was to study the influence of β-cyclodextrin (β-CD) on the biopharmaceutic properties of diclofenac (DCF). To this purpose the physicochemical characterization of diclofenac-β-cyclodextrin binary systems was performed both in solution and solid state. Solid phase characterization was performed using differential scanning calorimetry (DSC), powder x-ray diffractometry (XRD), and Fourier transform infrared spectroscopy (FTIR). Phase solubility analyses, and in vitro permeation experiments through a synthetic membrane were performed in solution. Moreover, DCF/β-CD interactions were studied in DMSO by1H nuclear magnetic resonance (NMR) spectroscopy. The effects of different preparation methods and drug-to-β-CD molar ratios were also evaluated. Phase solubility studies revealed 1∶1 M complexation of DCF when the freeze-drying method was used for the preparation of the binary system. The true inclusion for the freeze-dried binary system was confirmed by1H NMR spectroscopy, DSC, powder XRD, and IR studies. The dissolution study revealed that the drug dissolution rate was improved by the presence of CDs and the highest and promptest release was obtained with the freeze-dried binary system. Diffusion experiments through a silicone membrane showed that DCF diffusion was higher from the saturated drug solution (control) than the freeze-dried inclusion complexes, prepared using different DCF-β-CD molar ratios. However, the presence of the inclusion complex was able to stabilize the system giving rise to a more regular diffusion profile