Diamorphine hydrochloride is available as a lyophilized product in 10-, 30-, 100-, and 500-mg ampuls.38
Diamorphine hydrochloride is very soluble in water. Up to 100 mg can be reconstituted in 1 mL of diluent; a minimum of 2 mL of diluent is recommended for the 500-mg size. The preferred diluent is dextrose 5%, but sodium chloride 0.9% also may be used.1442
Diamorphine hydrochloride is given by intramuscular, intravenous, or subcutaneous injection. Administration can also be by slow continuous subcutaneous or intravenous injection with an infusion control device.38
Ampuls of lyophilized diamorphine hydrochloride should be stored at or below 25°C and protected from light.38
Diamorphine hydrochloride 1 mg/mL as an aqueous solution in flint glass ampuls stored at 25°C exhibited 10% loss in 50 days.1958
In another study, diamorphine hydrochloride up to 25 mg/mL in sterile water for injection was stable for up to 24 hours at ambient temperature when protected from light.1454
pH Effects
The stability of the reconstituted injection depends on its pH; it is most stable at acidic pH, around 3.8 to 4.41442 to pH 4.51958. Degradation increases greatly at neutral or basic pH1448.
Diamorphine hydrochloride exhibits a pH-dependent incompatibility in sodium chloride injection. To remain in solution, the pH must be below 6.1458 Solutions containing up to 250 mg/mL of diamorphine hydrochloride have been shown to be compatible in sodium chloride 0.9%.1457; 1458; 1459
Temperature Effects
Solutions of diamorphine hydrochloride in sterile water for injection at concentrations greater than 15 mg/mL exhibited precipitation when stored at 21 and 37°C for longer than two weeks. At concentrations of 1 to 250 mg/mL in sterile water for injection in glass containers, diamorphine hydrochloride was stable for eight weeks at -20°C, exhibiting less than 10% degradation. At 4°C, degradation was inversely related to concentration. Diamorphine hydrochloride 31 and 250 mg/mL was stable, but solutions containing 1 and 7.81 mg/mL showed 15 and 12% losses, respectively, after eight weeks of storage.1452
Syringes
The stability of diamorphine hydrochloride solutions containing 1 and 20 mg/mL in sodium chloride 0.9% in glass syringes was determined. At ambient temperature, diamorphine hydrochloride in glass syringes was stable for seven days at 1 mg/mL and for 12 days at 20 mg/mL. This was somewhat less than the drug’s stability at these concentrations in PVC containers; adequate stability was maintained for at least 15 days in PVC containers.1449
Diamorphine hydrochloride stability in plastic syringes was reported to be 14 days at room temperature and greater than 40 days at 4°C.982
Diamorphine hydrochloride (Hillcross) 2 and 20 mg/mL in water for injection was stored in plastic syringes (Becton Dickinson) sealed with blind hubs. A 5% loss occurred in 18 days at 20°C.1672
Infusion Pumps
Solutions containing diamorphine hydrochloride 250 mg/mL in an Act-a-Pump (Pharmacia) reservoir were stable for at least 14 days during simulated patient use.1450 Degradation was both temperature and concentration dependent. Solutions of diamorphine hydrochloride 1 mg/mL in water stored at 21°C for 42 days showed 10.6% degradation. At 37°C, 32.6% degradation occurred.1451
However, at a concentration of 250 mg/mL, diamorphine hydrochloride losses of 11 and 85.8% at 21 and 37°C, respectively1451, were partially attributed to precipitation.1452
Diamorphine hydrochloride (Evans Medical) 5 mg/mL in sterile water for injection was stable in Parker Micropump PVC reservoirs for 14 days at 4°C, exhibiting no loss. At 37°C, about a 2% loss occurred in seven days and a 7% loss occurred in 14 days.1696
Elastomeric Reservoir Pumps
Diamorphine hydrochloride 1 and 20 mg/mL in sodium chloride 0.9% was evaluated for stability in two elastomeric disposable infusion devices, Infusor (Travenol) and Intermate 200 (I.S.C.). The drug was stable for 15 days in most cases. However, solutions containing diamorphine hydrochloride 1 mg/mL in the Intermate reservoir stored at 31°C were only stable for two days.1449
For a list of references cited in the text of this monograph, search the monograph titled References.