Optimization of spray-dried porous microparticles preparation for pulmonary delivery.

Inhalation administration of dry powder particles is a common application route to achieve local and systemic drug effects. For pulmonary diseases, the deposition of drugs at the site of action is desirable. Thus, the parameters of the inhaled particles, especially their size, shape, or aerosolization, are essential for effective treatment. Suitable parameters can be achieved by choice of preparation method or excipients (carriers, porogens, or aerosolizing agents). This experiment aimed to prepare 11 batches of powder mixtures by spray drying, which differed in the carrier used and the amount of leucine or porogen. The aim was to optimize the formulation for drug binding concerning the requirements for pulmonary administration. The prepared particles were evaluated in terms of morphology, flow properties, porosity, and geometric and aerodynamic diameter. It was found that with increasing concentration of leucine, the bulk density of the particles decreased while the FPF value increased. Similarly, there was a decrease in MMAD. The batch containing 15% leucine was the most suitable. In determining the optimum porogen concentration for mannitol particles, the batch with its 1% gave the best results due to its adequate particle size compared to the other batches (MMAD 5.92 ± 1.32 µm), suitable porosity, and particle morphology. Thus, to formulate drug-loaded particles, it would be advisable to reduce the aerodynamic diameter of the particles, e.g., by spray drying process parameters.

Optimization of Spray Drying Process Parameters for the Preparation of Inhalable Mannitol-Based Microparticles Using a Box-Behnken Experimental Design.

Inhalation is used for local therapy of the lungs and as an alternative route for systemic drug delivery. Modern powder inhalation systems try to target the required site of action/absorption in the respiratory tract. Large porous particles (LPPs) with a size >5 µm and a low mass density (usually measured as bulk or tapped) of <0.4 g/cm3 can avoid protective lung mechanisms. Their suitable aerodynamic properties make them perspective formulations for deep lung deposition. This experiment studied the effect of spray-drying process parameters on LPP properties. An experimental design of twelve experiments with a central point was realized using the Box-Behnken method. Three process parameters (drying temperature, pump speed, and air speed) were combined on three levels. Particles were formed from a D-mannitol solution, representing a perspective material for lung microparticles. The microparticles were characterized in terms of physical size (laser diffraction), aerodynamic diameter (aerodynamic particle sizer), morphology (SEM), and densities. The novelty and main goal of this research were to describe how the complex parameters of the spray-drying process affect the properties of mannitol LPPs. New findings can provide valuable data to other researchers, leading to the easy tuning of the properties of spray-dried particles by changing the process setup.