Abstract
Subcutaneous (SC) ketamine has been found to be effective in pain management, though reports of injection site irritation and sterile abscesses exist with currently available ketamine HCl formulations. Such adverse SC reactions are commonly associated with low pH, high osmolality and/or high injection volumes. An optimal SC formulation of ketamine would thus have a pH and osmolality close to physiological levels, without compromising on concentration and, thus, injection volume. Such a formulation should also be buffered to maintain the pH at the acceptable level for extended time periods. As many of these physicochemical properties are interrelated, achieving these aims represented a significant challenge in formulation development. We describe the development of a novel Captisol®-based formulation strategy to achieve an elevated pH, isosmotic and buffered formulation of ketamine (hence, three birds, one excipient) without compromising on concentration. This strategy has the potential to be readily adapted to other amine-based APIs.