Production and downstream processing of API nanosuspensions
Most recently discovered active pharmaceutical ingredients (APIs) show insufficient water solubility accounting for poor bioavailability. One possibility to overcome these hindrances is comminution APIs by wet media milling. By reducing the particle size into the submicronic range the solubility of the APIs is increased in contrast to the coarse particles effectuating a significant increase in the bioavailability. However, nanosuspensions also show certain disadvantages. They are, for example, prone to hydrolytic degradation and tend to physical instabilities, such as agglomeration, aggregation or growth phenomena (Ostwald ripening) limiting their long term applicability. Therefore, the conversion of API nanosuspensions into the solid state by suitable drying methods (e.g. fluidized bed granulation, spray drying) is desired. For a final application the dry products need to be further processed e.g. into tablets. In this regard, the nanoparticulate integrity has to be preserved within the dry products and the final dosage form in order to maintain the advantageous properties of the originally applied nanosuspension. The main focus of the current research is therefore the influence of different formulation and process parameters along the process chain of production and drying API nanosuspensions, as well as compaction of the dry products into tablets.