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 for preparing a terminally sterilized injectable baclofen formulation suitable for injection into cerebrospinal fluid of a patient, the method comprising:
dissolving baclofen in aqueous solvent, selected from water, a saline solution, water containing phosphate or sulfate, or a saline solution containing sulfate or phosphate, to generate an initial solution, wherein the concentration of baclofen in the initial solution is between 0.05 mg/mL and 7 mg/mL;
adjusting the pH of the initial solution to between 5.0 and 6.2 to produce a pH adjusted solution; and
steam sterilizing the pH adjusted solution to achieve a sterility assurance level of 1×10 6 , producing a terminally sterilized solution, wherein the terminally sterilized solution, after storage of at least 30 days at room temperature, has a pH of between 5.0 and 7.0 and has less than 1.3% of 4-(4-chlorophenyl)-2-pyrrolidinone (4-CPP) based on the concentration of baclofen added to the initial solution.
2. The method of claim 1 , wherein the steam sterilizing comprises sterilizing to an F 0 for at least 15 minutes at 121° C.
3. The method of claim 1 , wherein the terminally sterilized solution, after storage of 6 months at room temperature, has a pH of between 5.0 and 7.0 and has less than 1.3% of 4-CPP.
4. The method of claim 1 , wherein the concentration of baclofen in the initial solution is between 0.05 mg/mL and 2 mg/mL.
5. The method of claim 1 , wherein the initial solution further comprises NaCl.
6. The method of claim 5 , wherein the initial solution comprises NaCl in an amount that provides the initial solution with an ionic strength equivalent to 0.15M NaCl.
7. The method of claim 1 , wherein the concentration of baclofen in the initial solution is about 0.05 mg/mL and wherein adjusting the pH of the initial solution comprises adjusting the pH to between 5.0 and 5.5.
8. The method of claim 1 , wherein the concentration of baclofen in the initial solution is about 0.5 mg/mL and wherein adjusting the pH of the initial solution comprises adjusting the pH to between 5.5 and 6.0.
9. The method of claim 1 , wherein the concentration of baclofen in the initial solution is about 2 mg/mL and wherein adjusting the pH of the initial solution comprises adjusting the pH to between 5.5 and 6.2.
10. The method of claim 1 , wherein the initial solution consists essentially of baclofen, NaCl and water.
11. The method of claim 1 , wherein adjusting the pH of the initial solution comprises adjusting the pH with HCl, H 2 SO 4 , H 3 PO or NaOH.