Spray Drying Tailored Mannitol Carrier Particles for Dry Powder Inhalation with Differently Shaped Active Pharmaceutical Ingredients

Abstract

Dry powder inhalation as commonly used in the local therapy of asthma or chronic obstructive pulmonary disease (COPD) is a very effective route of drug delivery. The system of small cohesive drug particles attached to the surface of large carriers with particle sizes >50 μm is successfully applied to numerous marketed products. The performance of these blends is based on the particle properties of both carriers and drug particles and is usually linked to the Fine Particle Fraction (FPF), which represents the fraction of drug particles with an aerodynamic diameter of 1–5 μm, which triggers the desired effect in the lung. Mannitol, which was chosen as an alternative carrier to the market-leading α-lactose monohydrate as it is highly crystalline in contrast to lactose even after spray drying, was prepared by spray drying to generate carrier particles at a range of 50–90 μm with various morphologies. This project was first aiming at the examination of the drying kinetics of bicomponent mannitol water droplets. It could be shown that high drying temperatures cause deep indentations and increasingly rough surface structures, while low drying temperatures result in spherical particles with rough surfaces at very low drying temperatures and smoother ones when increasing temperatures. Low rotation speeds and high mass fractions increase the particle size. Further particle properties like porosity, breaking strength or flowability were related accordingly. A defined set of mannitol batches was further selected for interactive powder blends with a micronised and spray dried quality of the model drug SBS. Particle–particle interactions were then investigated by correlating carrier properties to the resulting FPF. Particle shape was found to hinder the detachment of drug particles. Rough structures dried at the lowest drying temperatures were preferred for micronised drug particles, whereas spherical drug particles were preferably detached from smoother surfaces. This effect could be related to the drug size as only the detachment of the smallest drug particles (<1 μm) tended to be affected by the roughness. Carrier size was found to decrease the FPF for larger particles, when indentations occur simultaneously. Thus, it was possible to customise the carrier properties according to the drug particle properties to finally obtain adhesive drug–carrier mixtures with optimum aerodynamic performance.