Antibiyotik İçeren Kuru Toz İnhaler Formülasyonu Tasarımı ve Permeabilite Çalışmaları

Abstract

The aim of this thesis is to develope dry powder inhaler formulation with antibiotic and mucolytic combination to use in the treatment of the lung infection in cystic fibrosis disease. For this purpose, in this thesis, formulations containing ciprofloxacin and levofloxacin as antibiotics and acetylcysteine and DNase as mucolytics were prepared. Presence of a mucolytic in the same formulation will provide the penetration of the antibiotic by decreasing the mucus viscosity on the lung surface. Furthermore, the drug will be directly administered to site of action via inhaler formulation, and this will increase the efficiency and also prevent systemic side effects of the drug. To prepare the formulations, ball milling, homogenization and spray drying methods were used. Dry powder inhaler formulations were developed that had particles smaller than 5 µm in order to reach deeper areas of the lung. Besides the solubility studies, the dissolution study was performed for ciprofloxacin containing formulations. While the solubility was unchanged, the micronization accelerated the dissolution. FT-IR, DSC, TGA, XRD and SEM analysis were performed for active ingredients and the formulations, and results were consistent with the literature. Aerodynamic parameters were evaluated by Andersen Cascade Impactor, better aerosolization properties were obtained with levofloxacin containing formulations. Permeability studies were carried out with the Calu-3 cells, on both liquid covered and air interfaced culture. In the permeability studies, it was observed that, permeability of levofloxacin is higher than permeability of ciprofloxacin. Finally it was found that permeability values obtained from solution were lower than permeability values obtained from dry powder.