Suitability of Spray Dried Powder containing Lipids for Inhalation Formulation based on Fine Particle Fraction and Particle Size Distribution

Abstract: The aim of this master thesis is to provide an indication of the suitability, or otherwise usage, of spray-drying for production of powder aimed for inhalation formulation and comparing the characteristics of the product, with and without lipids. Lipids have a proven effect of delaying release of active drug substances in the cardiovascular system and pulmonary systemic delivery has a number of advantages, chiefly among them being bypassing the first pass metabolism. Incorporating lipids in an inhalation formulation would therefore be advantageous. Spray-drying is one of the proposed methods for production of such powder. There are numerous measurements needed to ascertain whether the product is suitable for a given formulation or not. This project will focus on the fine particle fraction and the particle size distribution, as well as miscellaneous measurements (for example, water activity and general particle shape). Two ingredients were essential in the formulation: The active pharmaceutical ingredient (API) and the lipid excipient. Lysozyme from egg white substituted for an API. Two lipids were tested, labeled “mixed lipid” and “pure lipid” respectively. The project was divided into three production trials and two analysis phases to gain information of how variations of different factors affect the properties. Obtained results show that the production system is robust and addition of lipids does not affect the properties adversely. Spray-drying produces spherical particles with low water content, if a high drying temperature and low feed rate is chosen. The fine particle fraction of the produced batches does not exceed 30 % and the size distribution shows the produced powder has no uniform particle size. The majority of the particle population have a large diameter with declining amount in lower diameters. Analysis of the results indicate an inhomogeneity in the final product, due to several irregularities and a large spread with the measured data. While no definite data was measured, possibilities of the discrepancies could be due to the preparation of the encapsulated substance rather than due to production via spray-drying.