Oral baclofen solutions
The present disclosure relates to aqueous oral solutions comprising baclofen. In one embodiment, the aqueous oral solutions comprise a buffer comprising citric acid, a salt of citric acid, or any combination thereof, and are stored at from about 2° C. to about 8° C. The present disclosure also relates to buffer free aqueous oral solutions comprising baclofen. Additionally, the present disclosure relates to an assay for determining the amount of an impurity, 4-(3-carboxymethyl)-3-hydroxy-2,5-dioxopyrrolidin-1-yl)-3-(4-chlorophenyl)butanoic acid, in a baclofen containing solution, and to methods of treatment using such aqueous oral solutions.
1 . A buffer-free aqueous oral solution consisting of:
(i) glycerin wetted baclofen, wherein the amount of glycerin is about 8 to about 12% w/v based on the volume of the solution;
(ii) methylparaben, propylparaben, or a combination thereof;
(iii) sucralose;
(iv) optionally a flavoring agent; and
(v) water;
wherein (i) the concentration of baclofen in the solution is about 2 mg/ml baclofen and (ii) the baclofen is completely dissolved in the solution.
2 . The buffer-free aqueous oral solution of claim 1 , wherein an amount of 4-(3-carboxymethyl)-3-hydroxy-2,5-dioxopyrrolidin-1-yl)-3-(4-chlorophenyl) butanoic acid in the solution after storage at 25° C. and 60% relative humidity for 6 months is less than about 0.2%.
3 . The buffer-free aqueous oral solution of claim 1 , wherein an amount of 4-(3-carboxymethyl)-3-hydroxy-2,5-dioxopyrrolidin-1-yl)-3-(4-chlorophenyl) butanoic acid after storage at 25° C. and 60% relative humidity for 6 months.
4 . The buffer-free aqueous oral solution according to claim 1 , wherein the solution is prepared by:
(a) wetting baclofen alone with glycerin;
(b) heating water and adding:
(i) sucralose,
(ii) a flavoring agent, and
(iii) methylparaben, propylparaben, or a combination thereof; to the water to form a mixture;
(c) adding the wetted baclofen from step (a) to the mixture of step (b) to form the oral solution.
5 . A buffer-free aqueous oral solution consisting of:
(i) glycerin wetted baclofen, wherein the concentration of glycerin is about 10% w/v based on the volume of the solution, and the concentration of baclofen is about 0.2% w/v based on the volume of the solution;
(ii) about 0.15% w/v methylparaben;
(iii) about 0.02% w/v propylparaben;
(iv) about 0.025% w/v sucralose;
(v) optionally about 1.0% w/v flavoring agent; and
(vi) water;
wherein the baclofen is completely dissolved in the solution.
6 . The buffer-free aqueous oral solution of claim 5 , wherein an amount of baclofen as measured by high performance liquid chromatography after 24 months of storage at room temperature is from about 90% to about 110%, based upon 100% of baclofen in the solution prior to storage.
7 . The buffer-free aqueous oral solution according to claim 5 , wherein the solution is prepared by
(a) wetting baclofen alone with glycerin,
(b) (i) heating water, (ii) adding sucralose, the flavoring agent, methylparaben, and propylparaben, to the water to form a mixture in which the methylparaben and propylparaben are completely dissolved, and (iii) reducing the temperature of the mixture to less than 25° C.,
(c) adding the wetted baclofen from step (a) to the mixture of step (b) to form the buffer-free aqueous oral solution.
8 . A method of dispensing to a patient a buffer-free aqueous oral solution comprising:
(i) storing the buffer-free aqueous oral solution of claim 5 at ambient temperature; and
(ii) dispensing the solution to a patient.
9 . A method of relaxing muscles or treating spasticity in a subject in need thereof comprising orally administering the buffer-free aqueous oral solution of claim 5 .