The Origins of HME as a Solubility Enhancement Manufacturing Technology

摘要

Hot melt extrusion (HME) is currently one of the cutting-edge solubility enhancement manufacturing technologies that pharmaceutical development scientists consider when formulating poorly-soluble drug substances. A look back on how it all started and how HME became a potent and enabling solubility enhancement manufacturing technology is illuminating. The technology was first introduced into the industry in 1991 when Warner-Lambert used HME to enhance the solubility of troglitazone, a very poorly soluble drug. Two years earlier, the company had acquired an early phase troglitazone drug product, which utilized a spray-drying process to enhance the solubility of the drug substance through the formation of an amorphous solid dispersion. Since Warner-Lambert did not have spray drying capability at the time, management asked Isaac Ghebre-Sellassie, who was Head of the Department of Technology Development at the time, and the founder and current owner of ExxPharma Therapeutics, to explore ways to convert the troglitazone spray-drying process to an alternative organic solvent-free manufacturing process. The spray-drying process was originally selected by the innovator after all commonly known amorphous solid dispersion solubilization methods cited in the literature (i.e., hot melt, hot melt/solvent evaporation and solvent evaporation processes) were investigated. Both melt processes, which utilized conventional granulating equipment, led to significant degradation at the melting point of the drug and had to be abandoned in favor of the organic solvent-based spray-drying process.