Intrathecal baclofen pharmaceutical dosage forms with fewer degradation products
View Patent ↗The present invention relates generally to a sterile, particulate-free, stable intrathecal baclofen solution with less than 0.5% of 4-(4-chlorophenyl)-2-pyrrolidone, a degradation product. These solutions are stable under a variety of storage conditions and for extended periods of time. Also disclosed are methods for preparing such compositions.
1. A sterile aqueous solution of baclofen sterilized by steam heating and containing 0.5% or less (by weight of baclofen) of 4-(4-chlorophenyl)-2-pyrrolidone, wherein baclofen in the solution is at a concentration from about 0.5 mg/mL to about 4.0 mg/mL.
2. The solution of claim 1 , further comprising sodium chloride.
3. The solution of claim 1 , wherein the solution contains 0.5% or less (by weight of baclofen) of 4-(4-chlorophenyl)-2-pyrrolidone after storage at 25° C. and 60% relative humidity for at least one year.
4. The solution of claim 1 , wherein the solution contains 0.5% or less (by weight of baclofen) of 4-(4-chlorophenyl)-2-pyrrolidone after storage at 40° C. and 75% relative humidity for at least two months.
5. The solution of claim 1 , wherein the baclofen concentration is from about 0.5 mg/mL to about 1.0 mg/mL.
6. The solution of claim 1 , wherein the baclofen concentration is from about 1.0 mg/mL to about 2.0 mg/mL.
7. The solution of claim 1 , wherein the baclofen concentration is from about 2.0 mg/mL to about 3.0 mg/mL.
8. The solution of claim 1 , wherein the baclofen concentration is from about 3.0 mg/mL to about 4.0 mg/mL.
9. The solution of claim 1 , wherein the solution is suitable for intrathecal delivery.
10. The solution of claim 1 , wherein the solution is free of particulates.
11. The solution of claim 1 , wherein the steam heating comprises heating the solution to 121.1° C. for a F 0 value of 7 minutes.
12. A vial containing the solution of claim 1 .
13. The vial of claim 12 , wherein the solution contains 0.5% or less (by weight of baclofen) of 4-(4-chlorophenyl)-2-pyrrolidone after storage at 25° C. and 60% relative humidity for at least one year.
14. The vial of claim 12 , wherein the solution contains 0.5% or less (by weight of baclofen) of 4-(4-chlorophenyl)-2-pyrrolidone after storage at 40° C. and 75% relative humidity for at least two months.