The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the inhaled air and pattern of deposition in the lung). With the development of advanced in vitro models, not only in vivo, but also cellular studies can be used for toxicological testing. Advanced in vitro studies use combinations of cells cultured in the air-liquid interface. These cultures are useful for particle uptake and mechanistic studies. Whole-body, nose-only, and lung-only exposures of animals could help to determine retention of NPs in the body. Both approaches also have their limitations; cellular studies cannot mimic the entire organism and data obtained by inhalation exposure of rodents have limitations due to differences in the respiratory system from that of humans. Simulation programs for lung deposition in humans could help to determine the relevance of the biological findings. Combination of biological data generated in different biological models and in silico modeling appears suitable for a realistic estimation of potential risks by inhalation exposure to NPs.

Hot-melt coating (HMC) as a solvent-free technology grants faster and more economic coating processes with reduced risk of dissolving the drug during the process. Moreover, traditional coating equipment can be modified to enable the HMC process. Despite the indubitable advantages and feasibility of the process, HMC is not well-known to pharmaceutical industry and its employment is still limited. The main aspect hindering the widespread application of this technique is the need of materials alternative to the conventional polymeric coatings. The current work reviews the published HMC formulations and describes the properties that have led to their selection. As these materials are mainly solid lipid excipients, attention should be paid to their crystallization and solid state behavior, and their impact on the performance of coated drug products, particularly on the stable drug release profile. Although different drug release profiles can be easily tailored, much development work is needed to respond to the unmet requirements of a stable formulation. Ensuring stable solid-state behavior and providing a mechanistic understanding of the macroscopic properties are essential steps towards fulfilling these requirements and establishing of HMC as advanced coating technology for manufacturing of pharmaceutical products.