Baclofen formulations and methods for making same
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 and/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.
2. The method according to claim 1 , wherein the solution has a pH of from 5.0 to 7.0.
3. 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.
4. The method of claim 3 , 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.
5. The method of claim 4 , 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.
6. The method of claim 1 , wherein the baclofen concentration is from 2.1 mg/mL to 7 mg/mL.
7. The method according to claim 6 , further comprising diluting the baclofen solution before administration.
8. The method of claim 1 , wherein the solution consists essentially of the baclofen, the sulfate and/or phosphate, sodium ion, and water.
9. The method of claim 1 , the solution 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.
10. The method of claim 9 , wherein the solution consists essentially of the baclofen, the sulfate and/or phosphate, sodium ion, chloride ion, and water.
11. The method of claim 1 , wherein the sulfate is derived from Na 2 SO 4 .
12. The method of claim 1 , wherein the phosphate is derived from NaH 2 PO 4 .
13. The method of claim 1 , wherein the solution has a pH of 6.0.
14. 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.
15. The method of claim 7 , wherein the diluting is performed with a diluting solution comprising sulfate and/or phosphate in a total 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 diluting solution has a pH between 5.5 and 6.5.
16. The method according to claim 15 , wherein the diluting reduces the concentration of 4-(4-chlorophenyl)-2-pyrrolidone (4-CPP) to less than 1.3%.
17. The method according to claim 7 , wherein the baclofen concentration after diluting is from 0.05 mg/mL to 4.0 mg/mL.
18. The method according to claim 17 , wherein the baclofen concentration after diluting is 0.05 mg/mL, 0.25 mg/mL, 0.5 mg/mL, 1.25 mg/mL, or 2.0 mg/mL.
19. A method for 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:
substantially pure L-baclofen in a concentration greater than 2 mg/mL, and
sulfate and/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.