Фармацевтика Аналитика Акта

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Preparation and characterization of Trimethoprim inclusion complex with Methyl-β-Cyclodextrin and determination of its antimicrobial activity

Ana Figueiras, Olga Cardoso, Francisco Veiga, Rusbene BF de Carvalho and Giorgia Ballaro

The present study focuses on the formation and characterization of inclusion complexes between Trimethoprim (TMP), an inhibitor of bacterial dihydrofolate reductase, and cyclodextrins, namely, methyl-βeta-cyclodextrin (MBCD) and hydroxylpropyl-βeta-cyclodextrin (HBCD) in aqueous solution. MBCD was selected to prepare inclusion complexes in the solid state. These complexes were prepared by different methods: spray drying, kneading and freeze drying. Physical mixtures were prepared as reference. The prepared systems were then characterized by different techniques: Differential scanning calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). The dissolution profile and the antimicrobial activity of Trimethoprim and the inclusion complexes were evaluated using the dissolution test, and the disk diffusion methodology, respectively. An increase of TMP solubility was observed in phase solubility studies. The obtained apparent stability constants (Ks) showed that MBCD formed an inclusion complex more stable with the drug than HPBCD, so it was decided to prepare inclusion complexes in solid state with MBCD. The results obtained with DSC, FTIR and SEM proved the formation of inclusion complexes in solid state. The dissolution profile and the antibacterial activity increased with the complexation process.