Pharmaceutical composition having uniform drug distribution and potency

Abstract

Pharmaceutical compositions having uniform drug distribution and potency utilizing laxofoxifene as an active ingredient and containing a silicon dioxide to reduce loss of the active ingredient during the manufacturing process and methods for manufacturing such compositions are disclosed.

What is claimed is:  
     
         1 . A pharmaceutical composition comprising a tablet core or capsule fill, the core or fill containing about 0.3 w/w % to about 14.0 w/w % of (-)-cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol; a prodrug thereof, or a pharmaceutically acceptable salt, hydrate or solvate of the compound or the prodrug, about 3.0 w/w % of a disintegrant, about 0.5 w/w % of a glidant, about 1.0 w/w % of a lubricant and about 81.0 w/w % to about 95.0 w/w % of a diluent/filler.  
     
     
         2 . The composition according to  claim 1  wherein the disintegrant is selected from the group consisting of sodium starch glycolate, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, polyvinylpyrrolidone, methyl cellulose, microcrystalline cellulose, powdered cellulose, lower alkyl-substituted hydroxypropyl cellulose, polacrilin potassium, starch, pregelatinized, starch and sodium alginate; the glidant is selected from the group consisting of silicon dioxide, talc and corn starch; the lubricant is selected from the group consisting of calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated vegetable oil, light mineral oil, magnesium stearate, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc and zinc stearate; and the diluent/filler is selected from the group consisting of lactose, mannitol, xylitol, dextrose, sucrose, sorbitol, compressible sugar, microcrystalline cellulose, powdered cellulose, starch, pregelatinized starch, dextrates, dextran, dextrin, dextrose, maltodextrin, calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, magnesium carbonate, magnesium oxide, poloxamers such as polyethylene oxide and hydroxypropyl methyl cellulose.  
     
     
         3 . The composition according to  claim 1  wherein the disintegrant is croscarmellose sodium; the glidant is silicon dioxide; the lubricant is magnesium stearate; the diluent/filler is lactose and microcrystalline cellulose.  
     
     
         4 . A pharmaceutical composition comprising a tablet core or capsule fill, the core or fill comprising about 0.3 w/w % (−)-cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol or a pharmaceutically acceptable salt thereof; about 70% w/w % lactose; about 25 w/w % microcrystalline cellulose; about 3 w/w % croscarmellose sodium; about 0.5 w/w % silicon dioxide; and about 1.0 w/w % magnesium stearate.  
     
     
         5 . A pharmaceutical composition comprising a tablet core or capsule fill, the core or fill comprising about 0.7 w/w % (-)-cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol or a pharmaceutically acceptable salt thereof; about 70% w/w % lactose; about 25 w/w % microcrystalline cellulose; about 3 w/w % croscarmellose sodium; about 0.5 w/w % silicon dioxide; and about 1.0 w/w % magnesium stearate.  
     
     
         6 . The pharmaceutical compositions of claims  1 ,  2 ,  3 ,  4  or  5 , wherein the composition is a tablet and the tablet is coated.  
     
     
         7 . The pharmaceutical compositions of claims  1 ,  2 ,  3 ,  4  or  5  wherein the (-)-cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol is in the form of the D-tartrate salt.