Physical and Chemical Stability of Hydromorphone Hydrochloride 1.5 and 80 mg/mL Packaged in Plastic Syringes

The objective of this study was to evaluate the physical and chemical stability of hydromorphone hydrochloride in concentrations of 1.5 and 80 mg/mL in 0.9% sodium chloride injection packaged in plastic syringes. Test samples of hydromorphone hydrochloride 1.5- and 80-mg/mL solutions were packaged as 20 mL of drug solution in 30-mL plastic syringes, sealed with plastic tip caps, and stored at 4 deg C and 23 deg C for 60 days and at -20 deg C and 37 deg C (temperature extremes that might be encounterd during shipping) for 2 days. Evaluations for physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed by means of visual observation in normal room light with a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. The chemical stability of the drug was evaluated by means of a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique. All samples of hydromorphone hydrochloride remained free of visible precipitation throughout the study. Those solutions stored at 4 deg C, 23 deg C, or 37 deg C exhibited little or no change in measured particulate burden and haze level. Freezing the solution resulted in an increase in microparticulate content that did not redissolve when the solution was warmed at room temperature. Little or no loss of hydromorphone hydrochloride occurred in any of the samples at any storage temperature throughout the study. Hydromorphone hydrochloride concentrations were found to be 95% or greater over 60 days at both 4 deg C and 23 deg C; concentrations were greater than 97% at both -20 deg C and 37 deg C after 2 days. Hydromorphone hydrochloride solutions at concentrations ranging from 1.5 to 80 mg/mL in 0.9% sodium chloride injection can be packaged in plastic syringes, stored, and shipped with little or no loss of drug. Freezing should be avoided.