Cyclodextrin Complexation of Fenofibrate by Co‐Grinding Method and Monitoring the Process Using Complementary Analytical Tools

Abstract

Solvent‐free preparation types for cyclodextrin complexation, such as co‐grinding, are technologies desired by the industry. However, in‐depth analytical evaluation of the process and detailed characterization of intermediate states of the complexes are still lacking in areas. In our work, we aimed to apply the co‐grinding technology and characterize the process. Fenofibrate was used as a model drug and dimethyl‐β‐cyclodextrin as a complexation excipient. The physical mixture of the two substances was ground for 60 min; meanwhile, samples were taken. A solvent product of the same composition was also prepared. The intermediate samples and the final products were characterized with instrumental analytical tools. The XRPD measurements showed a decrease in the crystallinity of the drug and the DSC results showed the appearance of a new crystal form. Correlation analysis of FTIR spectra suggests a three‐step complexation process. In vitro dissolution studies were performed to compare the dissolution properties of the pure drug to the products. Using a solvent‐free production method, we succeeded in producing a two‐component system with superior solubility properties compared to both the active ingredient and the product prepared by the solvent method. The intermolecular description of complexation was achieved with a detailed analysis of FTIR spectra.