Pharmaceutical Composition Containing Sympathomimetic Amine Salt and Co-distillable Additive

Abstract

A pharmaceutical composition is provided which contains a water soluble acid salt of a sympathomimetic amine, e.g., pseudoephedrine, and an additive, e.g., a volatile amine or other odorant, that is co-distillable, e.g., by steam distillation, with the sympathomimetic amine and/or its derivatives, e.g., its free base.

1 . A pharmaceutical composition comprising a mixture which contains: i) a water soluble acid salt of a sympathomimetic amine, and ii) an additive that is co-distillable with the sympathomimetic amine and/or its derivatives. 
     
     
         2 . (canceled) 
     
     
         3 . The pharmaceutical composition of  claim 1  wherein said additive is co-distillable with the free base of said sympathomimetic amine. 
     
     
         4 . The pharmaceutical composition of  claim 1  wherein said additive is co-steam distillable with said sympathomimetic amine and/or its derivatives. 
     
     
         5 . The pharmaceutical composition of  claim 4  wherein said additive is co-steam distillable with the free base of said sympathomimetic amine. 
     
     
         6 . The pharmaceutical composition of  claim 4  wherein said additive is co-steam distillable with the free base of said sympathomimetic amine or its derivatives and is substantially unextractable from said sympathomimetic amine and/or its derivatives. 
     
     
         7 . The pharmaceutical composition of  claim 6  wherein said additive is substantially unextractable by methanol extraction, n-hexane extraction, and/or acid/base extraction. 
     
     
         8 . The pharmaceutical composition of  claim 1  wherein the additive exhibits a vapor pressure at 100° C. which ranges from about 0.1 to about 10 times that of the sympathomimetic amine. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The pharmaceutical composition of  claim 1  wherein the sympathomimetic amine is selected from the group consisting of ephedrine, phenylpropanolamine, and pseudo ephedrine. 
     
     
         12 . (canceled) 
     
     
         13 . The pharmaceutical composition of  claim 1  wherein said additive comprises a volatile amine having a vapor pressure at 100° C. of a least about 2 mm Hg. 
     
     
         14 . The pharmaceutical composition of  claim 13  wherein said R 1  R 2 R 3 N wherein R 1 R 2  and R 3  are each individually selected from —H, phenyl, alkyl-substituted phenyl, aryl-substituted phenyl, benzylsubstituted phenyl, and/or C 1  to C 8  alkyl. 
     
     
         15 . The pharmaceutical composition of  claim 1  wherein said additive comprises an odorant. 
     
     
         16 . The pharmaceutical composition of  claim 15  wherein said odorant is co-distillable with said sympathomimetic amine or its derivatives. 
     
     
         17 . The pharmaceutical composition of  claim 16  wherein said odorant is co-steam distillable with said sympathomimetic amine or its derivatives. 
     
     
         18 . The pharmaceutical composition of  claim 17  wherein said additive comprises an odorant selected from the group consisting of camphor, triethyl citrate, menthol, methyl anthranil, methyl anthanilate, isoamyl acetate, geranyl acetate, linalool, alpha ionone, ortho-nitroacetophenone, and ortho-aminoacetophenone. 
     
     
         19 . The pharmaceutical composition of  claim 15  wherein said additive comprises a mixture of two or more odorants selected from the group consisting of esters, alcohols, hydrocarbons and amines. 
     
     
         20 . (canceled) 
     
     
         21 . The pharmaceutical composition of  claim 16  wherein said odorant is present in an amount sufficient to provide a product derived from distillation overhead wherein said product contains and odorant in an amount which is detectable by the mammalian sense of smell. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . The pharmaceutical composition of  claim 1  that comprises a further active ingredient. selected from the group consisting of a fewer reducer/pain reliever, an antihistamine, a cough suppressant/antitussive, an antihistamine/topical analgesic, and an expectorant. 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . A method of reducing the isolatability of a water soluble acid salt of a sympathomimetic amine from a pharmaceutical composition containing said acid salt of a sympathomimetic amine, which comprises including within said pharmaceutical composition a compound which is co-distillable with the sympathomimetic amine or its derivatives in an amount sufficient to reduce the purity of said amine or its derivatives recovered from a distillation overhead, as compared to said purity effected in the same manner except for the absence of said included compound. 
     
     
         32 . The method of  claim 31  wherein said compound is co-steam distillable with the sympathomimetic amine or its derivatives. 
     
     
         33 . The method of  claim 32  wherein said compound is substantially incapable of separation from said sympathomimetic amine or its derivatives by a method or methods selected from the group consisting of solvent extraction, precipitation, simple distillation, and crystallization. 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled)