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% 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. An aqueous, terminally sterilized pharmaceutical composition suitable for intrathecal delivery, wherein the composition comprises baclofen at a concentration of between about 0.5 mg/mL to about 4.0 mg/mL, and wherein the composition contains 0.5% (by weight of baclofen) or less 4-(4-chlorophenyl)-2-pyrrolidone.
2. The composition as recited in claim 1 further comprising:
a) sodium chloride and;
b) sterile water.
3. The composition as recited in claim 1 , wherein said composition is free of particulates.
4. The composition as recited in claim 1 , wherein said composition contains 0.5% (by weight of baclofen) or less of 4-(4-chlorophenyl)-2-pyrrolidone after storage at 25° C. and 60% relative humidity for at least 2 months.
5. The composition as recited in claim 1 , wherein said composition contains 0.5% (by weight of baclofen) or less of 4-(4-chlorophenyl)-2-pyrrolidone after storage at 40° C. and 75% relative humidity for at least 1 month.
6. The composition of claim 1 , wherein the concentration of baclofen is 0.5 mg/mL.
7. The composition of claim 1 , wherein the concentration of baclofen is 2.0 mg/ml.
8. The composition of claim 1 , wherein the concentration of baclofen is 3.0 mg/mL.
9. A method of manufacturing the pharmaceutical composition of claim 1 comprising the steps:
a) dissolving NaCl in water with stirring;
b) dissolving baclofen in said aqueous NaCl solution with stirring;
c) diluting said solution of NaCl and baclofen while stirring;
d) steam-heating said solution to 121.1° C. so that the F o for the resulting terminally sterilized solution is 7 minutes.
10. The method of claim 9 , wherein the concentration of baclofen is 0.5 mg/mL.
11. The method of claim 9 , wherein the concentration of baclofen is 2.0 mg/mL.
12. The method of claim 9 , wherein the concentration of baclofen is 4.0 mg/mL.
13. The composition as recited in claim 1 , wherein said composition contains 0.5% (by weight of baclofen) or less of 4-(4-chlorophenyl)-2-pyrrolidone after storage at 40° C. and 75% relative humidity for at least 2 months.