Baclofen formulations and methods for making same
View Patent ↗Methods for preparing sterilized baclofen solutions include adjusting the pH to below a desired pH, and steam sterilizing the solution with adjusted pH, which results in the solution having the desired pH. Such solutions may also have low concentrations of 4-CPP. Injectable baclofen solutions having greater than 2 mg/mL baclofen include between 5 mM and 25 mM of a phosphate or sulfate species. The solution has an ionic strength equivalent of about 1.5 M NaCl. The present application also provides baclofen formulations for use in treating spasticity, brain injury, cerebral palsy, spinal cord injury, cervical injury, multiple sclerosis, thoracic injury, or withdrawal symptoms.
1. A method of treating spasticity, brain injury, cerebral palsy, spinal cord injury, cervical injury, multiple sclerosis, or thoracic injury in a patient suffering therefrom, the method comprising administering, to the patient suffering therefrom, an injectable baclofen solution comprising:
baclofen in a concentration greater than 2 mg/mL; and
sulfate or phosphate in a concentration of between 10 mM and 25 mM,
wherein the solution has an ionic strength equivalent of between 1.4 M NaCl and 1.6 M NaCl, the solution comprising less than 1.3% of 4-(4-chlorophenyl)-2-pyrrolidone (4-CPP) after at least 30 days of storage at room temperature, wherein the solution has a pH between 5.5 and 6.5.
2. The method according to claim 1 , wherein the patient is suffering from spasticity.
3. A method of reducing or treating baclofen withdrawal symptoms in a patient suffering therefrom, the method comprising administering to the patient D-baclofen so as to reduce or treat the baclofen withdrawal symptoms.
4. The method according to claim 3 , wherein the amount of the D-baclofen administered to the patient is increased and the amount of L-baclofen or D-L baclofen administered to the patient is decreased.
5. The method of claim 1 , wherein the solution is sterilized and comprises 0.2% to 1.1% of 4-(4-chlorophenyl)-2-pyrrolidinone (4-CPP) after at least 30 days of storage at room temperature.
6. The method of claim 5 , wherein the solution is sterilized and comprises 0.2% to 1.1% of 4-(4-chlorophenyl)-2-pyrrolidinone (4-CPP) after at least 6 months of storage at room temperature.
7. The method of claim 6 , wherein the solution comprises 0.2% to 0.4% of 4-(4-chlorophenyl)-2-pyrrolidinone (4-CPP) after at least 6 months of storage at room temperature.
8. The method of claim 1 , wherein the baclofen concentration is from 2.1 mg/mL to 7 mg/mL.
9. The method according to claim 8 , wherein the baclofen solution is diluted before administration.
10. The method of claim 1 , wherein the solution consists essentially of the baclofen, the sulfate or phosphate, sodium ion, and water.
11. The method of claim 1 , further comprising NaCl, wherein the NaCl is present in an amount to provide the solution with an ionic strength equivalent to 1.5 M NaCl.
12. The method of claim 11 , wherein the solution consists essentially of the baclofen, the sulfate or phosphate, sodium ion, chloride ion, and water.
13. The method of claim 1 , wherein the sulfate is derived from Na 2 SO 4 .
14. The method of claim 1 , wherein the phosphate is derived from NaH 2 PO 4 .
15. The method of claim 1 , wherein the solution has a pH of 6.0.
16. The method of claim 1 , wherein the solution comprises 0.2% to 0.4% of 4-(4-chlorophenyl)-2-pyrrolidinone (4-CPP) after at least 30 days of storage at room temperature.
17. The method of claim 9 , wherein the baclofen solution is diluted with a solution comprising sulfate or phosphate in a concentration of between 10 mM and 25 mM, wherein the solution has an ionic strength equivalent of between 1.4 M NaCl and 1.6 M NaCl, wherein the solution has a pH between 5.5 and 6.5.
18. The method according to claim 17 , wherein the baclofen solution is diluted to reduce the concentration of 4-(4-chlorophenyl)-2-pyrrolidone (4-CPP) to less than 1.3%.
19. The method according to claim 9 , wherein the baclofen concentration after dilution is from 0.05 mg/mL to 4.0 mg/mL.
20. The method according to claim 19 , wherein the baclofen concentration after dilution is from 0.25 mg/mL to 1.25 mg/mL.
21. The method according to claim 19 , wherein the baclofen concentration after dilution is 0.05 mg/mL, 0.25 mg/mL, 0.5 mg/mL, 1.25 mg/mL, or 2.0 mg/mL.
22. A method of treating spasticity, brain injury, cerebral palsy, spinal cord injury, cervical injury, multiple sclerosis, or thoracic injury in a patient suffering therefrom, the method comprising diluting an injectable baclofen solution comprising:
baclofen in a concentration of from 2.1 mg/mL to 7 mg/mL; and
sulfate or phosphate in a concentration of between 10 mM and 25 mM,
wherein the solution has an ionic strength equivalent of between 1.4 M NaCl and 1.6 M NaCl, the solution comprising less than 1.3% of 4-(4-chlorophenyl)-2-pyrrolidone (4-CPP) after at least 30 days of storage at room temperature, wherein the solution has a pH between 5.5 and 6.5; and
administering the diluted baclofen solution to the patient suffering therefrom.
23. The method according to claim 22 , wherein dilution of the baclofen solution reduces the concentration of 4-(4-chlorophenyl)-2-pyrrolidone (4-CPP) to less than 1.2%.
24. The method according to claim 22 , wherein the baclofen concentration after dilution is from 0.05 mg/mL to 4.0 mg/mL.
25. The method according to claim 24 , wherein the baclofen concentration after dilution is from 0.25 mg/mL to 1.25 mg/mL.
26. The method according to claim 22 , wherein the administering is performed by an implantable pump in the patient.
27. The method according to claim 26 , wherein the implantable pump is an osmotic pump, a fixed rate or variable rate pump, a piston pump, or a peristaltic pump.
28. The method according to claim 26 , wherein the diluting of the baclofen solution occurs in the implantable pump.
29. The method according to claim 26 , wherein the diluting of the baclofen solution occurs in the reservoir.