Molecular 3D Characterisation of Drug Distribution and Mg-Stearate Coating on Lactose Carrier Particles by ToF-SIMS and XPS

A common type of inhalation medicine uses a dry powder formulation where the active pharmaceutical ingredient (API) is attached on the surface of carrier particles, often in combination with additional components. The spatial distribution of the API on the carrier particle is critical for the release into the lungs and thus for the efficacy of the drug. In this work, we use ToF-SIMS imaging in combination with argon gas cluster sputtering to determine the 3D distributions of budesonide (the API) and magnesium stearate (Mg-stearate) on the surface of lactose carrier particles in a so-called adhesive mixture formulation. The results show that the carrier particles are largely covered by Mg-stearate, with only small spots showing exposed lactose or budesonide. Upon sputtering, Mg-stearate is rapidly removed to expose flat regions of lactose as well as discrete budesonide particles distributed over the lactose surface. Depth profiles also indicate some smearing of budesonide on the lactose surface. These results provide clear evidence that budesonide, as well as lactose, is largely covered with Mg-stearate on the drug particle surface. Subsequent SEM analyses of the sample areas provide detailed microstructural information, including identification of budesonide and lactose fine particles attached on the lactose surface. Furthermore, the thickness of the Mg-stearate overlayer was estimated by XPS to be approximately 5 nm. The detailed information obtained about the 3D distribution of Mg-stearate serves to clarify the mechanisms behind its performance-enhancing effect in adhesive mixtures and also to improve formulation optimization with regard to Mg-stearate load and application process.