Preparation and characterization studies of natural polymer-based triamcinolone acetonide dry powder inhaler formulations

Asthma is a chronic and inflammatory airway disease in which many cells and cell components play a role, causing the airways to become extremely susceptible to varying stimuli and become narrower in time. The mechanisms of risk factors that provide the development and emergence of asthma are complex. These mechanisms interact with each other. The susceptibility to asthma is determined by the interaction of genes with other genes and with environmental factors. Asthma is seen in both children and adults around the world, and frequently followed by attacks. In recent years, the prevalence and incidence of asthma have increased significantly. In parallel with the increase in prevalence and incidence, the costs of treatment also bring burden on the economy of the country. It also reduces the quality of life of the patient in social sense. The prevalence of asthma in the world varies between 1% and 18%. Asthma is a costly disease for the patient and society. Asthma can be controlled by appropriate treatment and follow-up. Inhalation is the first choice method in the treatment of chronic diseases with current limitation in airways. Pharmaceutical companies also give importance to the development of inhaler formulations in recent years. The aim of asthma treatment is to minimize clinical symptoms, to reduce the frequency of attacks, to improve the quality of life of the patient, to correct lung function and to reduce the side effects that may occur due to long-term drug use. For these reasons, inhaled steroids are the most effective and most preferred anti-inflammatory drugs for the treatment of asthma. Among the corticosteroid group drugs, the commercially available metered dose inhaler (MDI) triamcinolone acetonide (TA), which was used in previous years, was removed from the market because of its propellant. Bronchospasm occurs when the medication and gas do not mix with each other during the use of a metered dose inhaler. In the patient who develops bronchospasm, shortness of breath complaints increases and negatively affects the treatment. This also causes the patient to discontinue treatment with the metered dose inhaler. It is also difficult to use because MDIs require hand - breathing coordination. Hydrofluoroalkanes which are used as propellant gas in metered dose inhalers pose a risk for the patient. Because of the disadvantages of MDIs and the abolition of the world pharmaceutical market, it is aimed to develop the dry powder inhaler formulations (TA) containing TA in our thesis, to optimize their effectiveness and to make a formulation design that can be used safely. In our thesis, TA loaded hyaluronic acid (HA) microparticulate dry powder inhaler ( DPI ) formulations were prepared by spray drying method. Characterization studies on the excipients and the prepared formulations, the capacity to store in the lungs, in vitro aerosol performance, flow properties and in vitro release kinetic analyzes with the new generation impulse device were performed. All the stages of this thesis were completed and the microparticular KTI formulations containing triamcinolone acetonide were prepared, and an innovative, effective and reliable formulation was designed for the treatment of asthma.