RESUMO
Amorphous solid dispersions (ASD) are one of the most prominent formulation approaches to overcome bioavailability issues that are often presented by new poorly soluble drug candidates. State-of-the art manufacturing techniques include hot melt extrusion and solvent-based methods like spray drying. The high thermal and mechanical shear stress during hot melt extrusion, or the use of an organic solvent during solvent-based methods, are examples of clear drawbacks for those methods, limiting their applicability for certain systems. In this work a novel process technology is introduced, called Nano-Dry-Melting (NDM), which can provide an alternative option for ASD manufacturing. NDM consists of a comminution step in which the drug is ground to nanosize and a drying step provides a complete amorphization of the system at temperatures below the melting point. Two drug-polymer systems were prepared using NDM with a wet media mill and a spray dryer and analyzed regarding their degree of crystallinity using XRD analysis. Feasibility studies were performed with indomethacin and PVP. Furthermore, a "proof-of-concept" study was conducted with niclosamide. The experiments successfully led to amorphous samples at temperatures of about 50 K below the melting point within seconds of heat exposition. With this novel, solvent-free and therefore "green" production technology it is feasible to manufacture ASDs even with those drug candidates that cannot be processed by conventional process technologies.
