Hydromorphone formulations for multi-dose products
The present disclosure relates to a multi-dose vial presentation for hydromorphone. In particular, the present disclosure relates to terminally sterilized liquid formulations comprising hydromorphone hydrochloride packaged in a multi-dose glass vial. The present disclosure also relates to methods of treating patients by administration of such formulations and glass vials containing such formulations.
1 . A glass vial filled with a multi-dose parenteral liquid formulation, the liquid formulation comprising:
(a) 2.0 mg/mL of hydromorphone hydrochloride;
(b) 0.5 mg/mL of edetate disodium;
(c) 1.8 mg/mL of methylparaben; and
(d) 0.2 mg/mL of propylparaben;
wherein the liquid formulation has a pH of 3.9 to 4.1,
wherein the liquid formulation is substantially free of citrate buffer,
wherein the liquid formulation has been terminally sterilized in a glass vial by autoclave wherein the terminal sterilization is characterized by an F 0 value from 10 to 20,
wherein the liquid formulation has not more than 0.3% w/w of 4-hydroxybenzoic acid and not more than 0.2% w/w of 7-hydroperoxylhydromorphone and 7-hydroxylhydromorphone after terminal sterilization and storage for up to 24 weeks at 25° C.±2° C. and 60% relative humidity (RH)±5% RH,
wherein the glass vial contains a 20 mL fill of the liquid formulation, and
wherein the vial has a headspace comprising not more than 8% oxygen.
2 . The glass vial of claim 1 , wherein the liquid formulation has not more than 0.1% w/w of 4-hydroxybenzoic acid after storage for up to 24 weeks at 25° C.±2° C. and 60% relative humidity (RH)±5% RH.
3 . The glass vial of claim 1 , wherein the liquid formulation retains at least 95% w/w of the hydromorphone hydrocholoride and has not more than 1% w/w of 2,2′-bishydromorphone and hydromorphone N-oxide after storage at 25° C.±2° C. and 60% RH±5% RH for up to 24 weeks.
4 . The glass vial of claim 1 , further comprising a pH adjusting agent.
5 . A method of treating a patient in need of management of pain comprising parenterally administering to the patient the liquid formulation contained in the glass vial of claim 1 .
6 . The method of claim 5 , wherein the pain is moderate to severe pain due to surgery, cancer, soft tissue and bone trauma, biliary colic, myocardial infarction, burns, or renal colic.
7 . The glass vial of claim 1 , wherein the liquid formulation has not more than 0.1% w/w of 2,2′-bishydromorphone after terminal sterilization and storage for up to 12 weeks at 40° C.±2° C. and 75% RH±5% RH.
8 . The glass vial of claim 1 , wherein the liquid formulation has not more than 0.4% 2,2′-bishydromorphone after terminal sterilization.