Oral baclofen solutions

Abstract

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 - 35 . (canceled) 
     
     
         36 . An aqueous oral solution comprising (i) baclofen wetted with glycerin and (ii) one or more preservatives, wherein (a) the solution contains 1 mg/mL baclofen as the sole active ingredient and from about 5 to about 15% w/v of glycerin and (b) the solution is stored at 2 to 8° C., wherein the solution contains less than about 0.2% of 4-(3-carboxymethyl)-3-hydroxy-2,5-dioxopyrrolidin-1-yl)-3-(4-chlorophenyl)butanoic acid. 
     
     
         37 . The oral solution of  claim 36 , wherein the solution comprises from about 8 to about 12% w/v of glycerin. 
     
     
         38 . The oral solution of  claim 36 , wherein the solution is prepared by
 (a) wetting baclofen with glycerin,   (b) heating water and adding one or more preservatives and optionally other components to the water to form a mixture,   (c) adding the wetted baclofen from step (a) to the mixture of step (b) to form an oral solution comprising 1 mg/mL baclofen as the sole active ingredient, from about 8 to about 12% w/v of glycerin, and one or more preservatives, and   (d) storing the solution at from about 2 to about 8° C., wherein the solution contains less than about 0.2% of 4-(3-carboxymethyl)-3-hydroxy-2,5-dioxopyrrolidin-1-yl)-3-(4-chlorophenyl)butanoic acid.   
     
     
         39 . The oral solution of  claim 36 , wherein the one or more preservatives are selected from methylparaben, propylparaben, sodium benzoate, sodium methylparaben, or any combination of any of the foregoing. 
     
     
         40 . The oral solution of  claim 36 , wherein the one or more preservatives are selected from methylparaben, propylparaben, or any combination of any of the foregoing. 
     
     
         41 . The oral solution of  claim 36 , wherein the solution further comprises sucralose and a flavoring agent. 
     
     
         42 . The oral solution of  claim 36 , wherein the solution comprises
 (i) about 0.15% w/v methylparaben;   (ii) about 0.02% w/v propylparaben;   (iii) about 0.025% w/v sucralose;   (iv) about 1.0% w/v flavoring agent; and   
     
     
         43 . The oral solution of  claim 42 , wherein the solution contains less than about 0.05% 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. 
     
     
         44 . An aqueous oral solution comprising (i) baclofen wetted with glycerin and (ii) one or more preservatives, wherein (a) the solution contains 1 mg/mL baclofen as the sole active ingredient and (b) the solution is stored at 2 to 8° C., wherein the solution contains less than about 0.2% of 4-(3-carboxymethyl)-3-hydroxy-2,5-dioxopyrrolidin-1-yl)-3-(4-chlorophenyl)butanoic acid. 
     
     
         45 . The oral solution of  claim 44 , wherein the solution further comprises methylparaben, propylparaben, sucralose, and a flavoring agent. 
     
     
         46 . A method of relaxing muscles or treating spasticity in a subject in need thereof comprising:
 (a) preparing an aqueous oral solution comprising (i) 1 mg/mL baclofen as the sole active ingredient wetted with glycerin and (ii) one or more preservatives,   (b) measuring the content of impurities in the solution to be less than about 0.2% of 4-(3-carboxymethyl)-3-hydroxy-2,5-dioxopyrrolidin-1-yl)-3-(4-chlorophenyl)butanoic acid;   (c) storing the solution from step (b) at 2 to 8° C.; and   (d) orally administering the solution to the subject.   
     
     
         47 . The method of  claim 46 , wherein the solution further comprises methylparaben, propylparaben, sucralose, and a flavoring agent. 
     
     
         48 . The method of  claim 46 , wherein the solution contains less than about 0.2% 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. 
     
     
         49 . The method of  claim 46 , wherein the solution comprises
 (i) about 0.15% w/v methylparaben;   (ii) about 0.02% w/v propylparaben;   (iii) about 0.025% w/v sucralose;   (iv) about 1.0% w/v flavoring agent; and   (v) about 10% w/v glycerin.