DRY POWDER FOR INHALATION - INFLUENCE OF MIXING PROCESS AND ADDITION OF MAGNESIUM STEARATE

Abstract: For efficient treatment of many diseases of the lung, it is beneficial to deliver the medicine to the respiratory tract directly. This ensures a rapid response since it can enter the bloodstream directly through the alveolar epithelium. Consequently, also decreases systemic effects due to the local treatment. Dry powder inhaler (DPI) is today one of the most used inhalers for pulmonary delivery. The DPI formulations often consist of a micronized active pharmaceutical ingredient (API) which is mixed with larger carrier particles, creating an adhesive mixture. For a successful API delivery, there are four main factors that need to be considered; the formulation, the device used for the delivery, the physicochemical properties of the drug and the patient. In this thesis, the focus is to determine how the mixing energy, mixing speed, mixing time and use of coatings, affects the formulation and drug delivery. These effects were studied using a Turbula T2C low shear and a Diosna P1-6 high shear mixer, set to different mixing speeds and mixing times to manufacture prototype formulations. To some of the batches, a coating of Magnesium Stearate was added. The formulations were studied using different analytical techniques. Evidently, all the above-mentioned parameters play a part in the performance of the formulations. However, it is indicated that it is rather the mixing energy that controls the quality, than the individual parameters. Neither too low nor too high mixing energy is beneficial when manufacturing formulations. Comparing the results of the Diosna and Turbula mixed formulations, it may be assumed that both are suitable for mixing of the API, however when mixing the coating agent, the Diosna high-shear mixer is favored. Adding a coating agent continually improved the performance of all formulations manufactured.