Nano-Dry-Melting: A Novel Technology for Manufacturing of Pharmaceutical Amorphous Solid Dispersions.

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.