Chitosan-based Triamcinolone Acetonide Dry Powder Inhaler Formulation, Preparation And Characterization Studies.
Project no. 259 · Status: Kapanmış · 2016
Summary
Asthma is a chronic and inflammatory airway disease, characterized with the reversible obstruction in the airflow of the lungs, in which many cells and cell components take place. In recent years, asthma’s prevalence and incidence have been presented to have increased considerably. This increase is especially clear in developed countries. Since this rise increases the treatment costs substantially, by social means it has lowered the quality of life as well as bringing burden to country’s economy. Especially regarding this reason, solution seeking on asthma treatment has been an important subject, which has been emphasized intensely in recent years. Inhalation is the leading treatment form in treatments of chronic diseases such as asthma, which appears in airways with flow limitation. Competition in development of inhaler formulations among pharmaceutical companies increases day by day. According to TechNavio analysis, production of inhaler medicines in the world has shown an increase of 6.3% in the past 4 years and it has been stated that this ratio will be increasing rapidly. Inhaler steroids are the most effective antiinflammatory medicines that are used in the treatment of persistent asthma. Studies have shown the efficiency of these medicines in reducing of attack frequency and level of air way inflammation and controlling the asthma in patients. Triamcinolone acetonide (TA), used frequently among corticosteroid group medicines, has metered dose inhalers (MDI) in the world market, commercially. Utilizations of MDIs are risky due to hydrochloroalkane content as propellant. In case of not providing the mixture of the drug and gas before MDI utilization, only repulsive gas passes through the patient’s airways, asthma symptoms of the patient increases due to bronchospasm. This situation causes to decrease the compliance of the patient as well as giving up the utilization of MDI. Furthermore, because it requires hand-respiration coordination, MDIs are not easy to use. Within the scope of the thesis, which has been suggested because of the disadvantages of the MDIs, it has been aimed to develop chitosan microparticulate dry powder inhaler (DPI) formulations containing TA, optimize their efficiency, and design a formulation that can be used with reliance. The suggested project has been planned in two stages. In the first stage; DPI that includes chitosan microparticulate DPI loaded with TA, were prepared by spray drying method. Characterization studies were carried out on excipients and formulations, storage capacity of active agent in pulmonary, in vitro aerosol performance by new generation impactor and flow features were examined. Studies were carried out in vitro drug release of DPI formulations, kinetic analysis of drug release. In the second stage; efficiency of DPI formulations that have high in vitro aerosol performance, DPI formulations were evaluated with cell culture study by using Calu-3 cell line. Innovative, effective and reliable formulations for asthma therapy has been designed by preparing microparticulate dry powder inhaler formulations containing TA completed with all the steps of this thesis as targeted. Keywords: Triamcinolone acetonide, asthma, dry powder inhaler, Calu-3, spray drying.