Stable parenteral DNJ compositions
View Patent ↗A stable pharmaceutical composition that includes an active agent selected from 1-deoxynojirimycin, a pharmaceutically acceptable salt thereof, or a derivative thereof, and a buffer, wherein the stable pharmaceutical composition is capable of being parenterally administered to a human without deleterious health effects. Pompe disease is an example of a lysosomal storage disorder. Pompe disease is caused by a deficiency in the enzyme acid alpha-glucosidase (GAA). GAA metabolizes glycogen, a storage form of sugar used for energy, into glucose.
1. A stable pharmaceutical composition comprising:
a) an active agent selected from 1-deoxynojirimycin, a pharmaceutically acceptable salt thereof, or a derivative thereof, and
b) a citrate buffer,
wherein the stable pharmaceutical composition is capable of being parenterally administered to a human without deleterious health effects and wherein the active agent is present at a concentration of from about 1 mg/mL to about 100 mg/mL.
2. The stable pharmaceutical composition of claim 1 , wherein the active agent is 1-deoxynojirimycin hydrochloride.
3. The stable pharmaceutical composition of claim 1 , wherein the active agent is N-butyl-deoxynojirimycin, or a pharmaceutically acceptable salt thereof.
4. The stable pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for subcutaneous administration.
5. The stable pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for intravenous administration.
6. The stable pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is at a pH of from about 4.6 to about 5.5.
7. The stable pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is at a pH of about 5.
8. The stable pharmaceutical composition of claim 1 , wherein the active agent is present at a concentration of from about 1 mg/mL to about 60 mg/mL.
9. The stable pharmaceutical composition of claim 1 , wherein the active agent is present at a concentration of from about 25 mg/mL to about 30 mg/mL and the buffer is present at a concentration of about 50 mM.
10. The stable pharmaceutical composition of claim 1 , wherein the total amount of active agent is about 300 mg and the total volume of the composition is about 10.5 mL.
11. The stable pharmaceutical composition of claim 1 , further comprising a chelating agent.
12. The stable pharmaceutical composition of claim 11 , wherein the chelating agent is EDTA.
13. The stable pharmaceutical composition of claim 12 , wherein the active agent is present at a concentration of about 30 mg/mL or about 25 mg/ml, the buffer is present at a concentration of about 50 mM, and EDTA is present at a concentration of about 0.05% weight by volume.
14. The stable pharmaceutical composition of claim 1 , wherein the composition is shelf-stable for at least about one year under an atmosphere selected from nitrogen, air or a combination thereof, and a temperature of from about 2° C. to about 42° C.
15. A method for increasing the stability of an active agent selected from 1-deoxynojirimycin, a pharmaceutically acceptable salt thereof, or a derivative thereof in a formulation for a parenteral administration to a human, comprising introducing a citrate buffer to the active agent to prepare the formulation and storing the formulation under an atmosphere selected from nitrogen, air or a combination thereof, and at a temperature of from about 2° C. to about 42° C., wherein the active agent is present at a concentration of from about 1 mg/ml to about 100 mg/mL.
16. The method of claim 15 , wherein the 1-deoxynojirimycin derivative formulation is shelf-stable for at least about one year.
17. The stable pharmaceutical composition of claim 1 , wherein the active agent is 1-deoxynojirimycin.
18. The stable pharmaceutical composition of claim 1 , wherein the composition is shelf-stable for at least about one year under a nitrogen atmosphere and a temperature of from about 2° C. to about 8° C. or from about 23° C. to about 27° C. or from about 38° C. to about 42° C.
19. The method of claim 15 , wherein the 1-deoxynojirimycin derivative formulation is shelf-stable at a temperature of from about 2° C. to about 8° C. or from about 23° C. to about 27° C. or from about 38° C. to about 42° C.
20. The stable pharmaceutical composition of claim 14 , wherein the composition is shelf-stable for at least about one year under a nitrogen atmosphere.
21. The method of claim 15 , wherein the 1-deoxynojirimycin derivative formulation is shelf-stable for at least about one year under a nitrogen atmosphere.