Spray Drying of Cocrystals for Engineering Particle Properties : Diploma Work
Sammanfattning: The goals of this work were to combine crystal and particle engineering in a single step using spray drying and improve particle properties that can potentially minimize the need for coating agents. Specific aim was to prepare and characterize theophylline cocrystal particles intended for inhalation using by spray drying. Theophylline is a bronchodilator used in the treatment of asthma and is used as a model drug in this study. Theophylline cocrystals with citric acid, flufenamic acid and saccharin were chosen as model systems. The solubilities of different components of cocrystals in different solvents were determined to get an idea of the stability landscape of cocrystals. Thereafter, the cocrystals were prepared by slurry crystallization method. The cocrystal particles from similar solutions were prepared using spray drying. The processing variables are carefully chosen for optimal particle engineering. The resulting solids were subjected to different characterizations such as particle size analysis, tap density and bulk density analysis and new generation impactor studies. Theophylline cocrystals were successfully obtained by both slurry crystallization and spray drying methods. Despite rapid drying, spray dried particles were predominantly crystalline with a particle size and other attributes suitable for inhalation. However, the process yields were low due to adhesion to cyclone walls. The impactor results indicated a decent aerosolization performance of the spray dried particles in pure and when blended with lactose. The cocrystal particles with interesting properties suitable for inhalation application can be prepared in one step using spray drying. The mechanisms behind reasons for adhesion of cocrystal particles should be further elucidated. Key words: spray drying, cocrystals, cocrystallization, coformers, particle engineering, design of experiments, inhalation, theophylline, citric acid, flufenamic acid, saccharin.
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