Method and composition for pharmaceutical product

Abstract

This invention is directed to a composition comprising dry granulated tenofovir DF and emtricitabine, and a method for making same. Dry granulation was unexpectedly found to be important in preparing a tenofovir DF containing composition suitable for inclusion in a combination dosage form containing emtricitabine, efavirenz and tenofovir DF.

What is claimed: 
     
         1 . A composition comprising dry granulated emtricitabine and tenofovir DF. 
     
     
         2 . The composition of  claim 1  wherein the water content (Karl Fischer) is about from 0.1 to 10% by weight. 
     
     
         3 . The composition of  claim 1  wherein the bulk density of the granules is about from 0.1 to 1 g/mL. 
     
     
         4 . The composition of  claim 1  wherein the geometric mean diameter of the granules is about from 50 to 800 micrometers. 
     
     
         5 . The composition of  claim 1  further comprising a pharmaceutically acceptable disintegrant. 
     
     
         6 . The composition of  claim 5  wherein the disintegrant is croscarmellose sodium or crospovidone. 
     
     
         7 . The composition of  claim 1  further comprising a pharmaceutically acceptable filler. 
     
     
         8 . The composition of  claim 1  further comprising a pharmaceutically acceptable binder. 
     
     
         9 . The composition of  claim 1  further comprising a pharmaceutically acceptable lubricant. 
     
     
         10 . The composition of  claim 1  as a unitary dosage form. 
     
     
         11 . The composition of  claim 10  which is a tablet. 
     
     
         12 . The composition of  claim 1  wherein the amount of emtricitabine and tenofovir DF is greater than about 70% by weight of the granules. 
     
     
         13 . The composition of  claim 12  wherein the amount of emtricitabine and tenofovir DF is about 77% by weight of the granules. 
     
     
         14 . The composition of  claim 1  which further comprises at least one pharmaceutically acceptable excipient. 
     
     
         15 . The composition of  claim 1  comprising (by approximate weight percent) emtricitabine 30.6, tenofovir DF 46.0, microcrystalline cellulose 13.7, croscarmelose sodium 7.3 and magnesium stearate 2.2. 
     
     
         16 . The composition of  claim 1  wherein the LOD is about 10%. 
     
     
         17 . A method comprising granulating a composition comprising emtricitabine and tenofovir DF without contacting the composition with a destabilizing amount of liquid water. 
     
     
         18 . The method of  claim 17  wherein liquid water is not combined with the composition prior to or during granulation. 
     
     
         19 . The method of  claim 17  wherein the composition further comprises at least one pharmaceutically acceptable excipient. 
     
     
         20 . The method of  claim 17  wherein granulation comprises aggregating the composition and comminuting it to desired dimensions. 
     
     
         21 . The method of  claim 20  wherein the aggregation is accomplished by slugging or roller compaction. 
     
     
         22 . The method of  claim 20  wherein the composition is sieved to recover granules of the desired dimensions. 
     
     
         23 . The method of  claim 22  wherein the granules are retained by a 1.25 mm mesh. 
     
     
         24 . The method of  claim 19  wherein the excipient is a lubricant. 
     
     
         25 . The method of  claim 24  wherein the lubricant is an alkali metal salt of a C8-C18 fatty acid. 
     
     
         26 . A unitary dosage form made by a process comprising dry granulation of a composition comprising emtricitabine and tenofovir DF. 
     
     
         27 . A composition comprising greater than about 75% by weight emtricitabine and tenofovir DF. 
     
     
         28 . A composition comprising granules comprising tenofovir DF, emtricitabine and croscarmellose sodium in an extragranular matrix also comprising croscarmellose sodium. 
     
     
         29 . A method for antiviral therapy comprising administering an antivirally effective amount of the composition of  claim 1  to a patient in need of antiviral therapy. 
     
     
         30 . The method of  claim 29  wherein the antiviral therapy is anti-HIV therapy.