In-die compression analysis is an effective method for the characterization of powder compressibility. However, physically unreasonable apparent solid fractions above one or apparent in-die porosities below zero are often calculated for higher compression stresses. One important reason for this is the neglect of solid compressibility and hence the assumption of a constant solid density. In this work, the solid compressibility of four pharmaceutical powders with different deformation behaviour is characterized using mercury porosimetry. The derived bulk moduli are applied for the calculation of in-die porosities. The change of in-die porosity due to the consideration of solid compressibility is for instance up to 4% for microcrystalline cellulose at a compression stress of 400 MPa and thus cannot be neglected for the calculation of in-die porosities. However, solid compressibility and further uncertainties from, for example the measured solid density and from the displacement sensors, are difficult or only partially accessible. Therefore, a mathematic term for the calculation of physically reasonable in-die porosities is introduced. This term can be used for the extension of common mathematical models, such as the models of Heckel and of Cooper & Eaton. Additionally, an extended in-die compression function is introduced to precisely describe the entire range of in-die porosity curves and to enable the successful differentiation and quantification of the compression behaviour of the investigated pharmaceutical powders.

The particle size reduction of active pharmaceutical ingredients is an efficient method to overcome challenges associated with a poor aqueous solubility. With respect to stability and patient’s convenience, the corresponding nanosuspensions are often further processed to solid dosage forms. In this regard, the influence of several formulation parameters (i.e., type of carrier material, type and amount of additional polymeric drying excipient in the nanosuspension) on the redispersibility of naproxen nanoparticle-loaded granules produced in a fluidized bed process was investigated. The dissolution rate of the carrier material (i.e., sucrose, mannitol, or lactose) was identified as a relevant material property, with higher dissolution rates (sucrose > mannitol > lactose) resulting in better redispersibility of the products. Additionally, the redispersibility of the product granules was observed to improve with increasing amounts of polymeric drying excipient in the nanosuspension. The redispersibility was observed to qualitatively correlate with the degree of nanoparticle embedding on the surface of the corresponding granules. This embedding was assumed to be either caused by a partial dissolution and subsequent resolidification of the carrier surface dependent on the dissolution rate of the carrier material or by resolidification of the dissolved polymeric drying excipient upon drying. As the correlation between the redispersibility and the morphology of the corresponding granules was observed for all investigated formulation parameters, it may be assumed that the redispersibility of the nanoparticles is determined by their distance in the dried state.