Finished Pharmaceutical Dosage Form Of A Methenamine Salt Such As Methenamine Mandelate

Abstract

The present invention contemplates a high dose finished pharmaceutical dosage form comprising a methenamine salt, such as methenamine mandelate, as an active pharmaceutical ingredient wherein the methenamine salt API has a moisture content that is less than the upper limit specified in the USP. A preferred embodiment of the present invention has a moisture content that is half of the limit set forth in the USP for each particular methenamine salt. An even more preferred embodiment has a moisture content of less than or equal to one-tenth of a percent (0.1%), regardless of the methenamine salt. The present invention may include one or more pharmaceutically acceptable ingredients. The present invention also contemplates a moisture content of the high dose finished pharmaceutical dosage form that is less than one percent.

1 . A finished pharmaceutical dosage form comprising:
 a methenamine mandelate active pharmaceutical ingredient having a moisture content of no more than one-tenth of a percent by weight based on a total weight of the methenamine mandelate, the methenamine mandelate being present in an amount of at least about 75% by weight of the finished pharmaceutical dosage form, and the finished pharmaceutical dosage form having a total moisture content of less than one percent based on a total weight of the finished pharmaceutical dosage form.   
     
     
         2 . The finished pharmaceutical dosage form of  claim 1 , wherein the finished pharmaceutical dosage form is a tablet. 
     
     
         3 . The finished pharmaceutical dosage form of  claim 1 , wherein the active pharmaceutical ingredient is present in an amount of 500 mg. 
     
     
         4 . The finished pharmaceutical dosage form of  claim 1 , wherein the active pharmaceutical ingredient is present in an amount of 1000 mg. 
     
     
         5 . The finished pharmaceutical dosage form of  claim 1 , wherein the moisture content of the methenamine mandelate active pharmaceutical ingredient is measured by the general physical USP test, Loss on Drying <731>. 
     
     
         6 . A tablet comprising:
 at least one pharmaceutically acceptable excipient; and   a methenamine salt active pharmaceutical ingredient having a moisture content of less than a moisture content specification set by the USP monograph for the methenamine salt, the methenamine salt being present in an amount of at least about 75% by weight of the finished pharmaceutical dosage form;   the tablet having a total moisture content of less than one percent based on a total weight of the tablet.   
     
     
         7 . The tablet of  claim 6 , wherein the methenamine salt is methenamine mandelate having a moisture content of no more than one-tenth of a percent by weight based on a total weight of the methenamine mandelate. 
     
     
         8 . The tablet of  claim 6 , wherein the pharmaceutically acceptable excipient comprises a diluent, a binder, a filler, a disintegrant, a glidant, a lubricant, or any combination thereof. 
     
     
         9 . The tablet of  claim 6 , wherein the pharmaceutically acceptable excipient comprises starch, microcrystalline cellulose, hydroxypropyl cellulose, povidone, lactose, dicalcium phosphate, croscarmellose sodium, sodium starch, glycolate, cross-linked polyvinyl pyrrolidone, silica, talc, stearic acid, magnesium stearate, sodium stearyl fumarate, or any combination thereof. 
     
     
         10 . The tablet of  claim 8 , wherein the pharmaceutically acceptable excipient is a binder. 
     
     
         11 . The tablet of  claim 8 , wherein the pharmaceutically acceptable excipient is a lubricant. 
     
     
         12 . The tablet of  claim 8 , wherein the pharmaceutically acceptable excipient is a binder or a lubricant. 
     
     
         13 . The tablet of  claim 6 , wherein the active pharmaceutical ingredient is present in an amount of 500 mg. 
     
     
         14 . The tablet of  claim 6 , wherein the active pharmaceutical ingredient is present in an amount of 1000 mg. 
     
     
         15 . The tablet of  claim 7 , wherein the moisture content of the methenamine mandelate is measured by the general physical USP test, Loss on Drying <731>. 
     
     
         16 . A process of making a high dose tablet of methenamine mandelate comprising:
 providing 500 or 1,000 milligrams of methenamine mandelate having a reduced moisture content of 0.1% or less;   blending the methenamine mandelate with a sufficient amount of at least one pharmaceutically acceptable excipient so as to form a tablet comprised of at least about 75% methenamine mandelate by weight of the tablet to form a blend, and   compressing the blend into a tablet with a total moisture content of less than 1%.   
     
     
         17 . The process of  claim 16 , wherein the pharmaceutically acceptable excipient comprises starch, microcrystalline cellulose, hydroxypropyl cellulose, povidone, lactose, dicalcium phosphate, croscarmellose sodium, sodium starch, glycolate, cross-linked polyvinyl pyrrolidone, silica, talc, stearic acid, magnesium stearate, sodium stearyl fumarate, or any combination thereof. 
     
     
         18 . A tablet of 500 mg methenamine mandelate made by the process of  claim 16 . 
     
     
         19 . A tablet of 1,000 mg methenamine mandelate made by the process of  claim 16 .