Solid oral film dosage forms and methods for making same

Abstract

Oral film dosage forms that provide improved solubilization and stabilization of an active ingredient in particle form include at least one primary crystallization inhibitor in an amount that inhibits growth and/or agglomeration of the active ingredient, a polyoxyethylated fatty acid glycerides in an amount that further enhances inhibition of crystallization, growth and agglomeration of the particles of the pharmaceutically active ingredient; and at least one plasticizer present in an amount that is effective to increase flexibility and elasticity of the film dosage form.

We claim: 
     
         1 . An oral film dosage form comprising:
 at least one active pharmaceutical in the form of particles; and   a polymer film matrix in which the active pharmaceutical particles are dispersed, the polymer film matrix including (a) at least one crystallization inhibitor selected from polyvinyl pyrrolidone, polyethylene oxide and poloxamer in an amount that inhibits growth and agglomeration of the active pharmaceutical particles, (b) from 15% to 19% by mass of the film dosage form of at least one substance that exists as a liquid at 37° C. and that enhances inhibition of growth and agglomeration of the active pharmaceutical particles; and (c) at least one plasticizer in an amount that is effective to increase flexibility of the film dosage faun.   
     
     
         2 . The dosage form of  claim 1 , wherein the substance that enhances inhibition of growth and agglomeration of the active pharmaceutical particles is a polyoxyethylated glyceride. 
     
     
         3 . The dosage form of  claim 2 , wherein the polyoxyethylated glyceride comprises at least one of oleoyl polyoxyl-6 glycerides, linoleoyl polyoxyl-6 glycerides, and lauroyl polyoxyl-6 glycerides. 
     
     
         4 . The dosage form of  claim 1 , wherein the active pharmaceutical ingredient is tadalafil. 
     
     
         5 . The dosage form of  claim 1 , in which the amount of the crystallization inhibitor is from about 25% to about 85% of the mass of the film dosage form. 
     
     
         6 . The dosage form of  claim 1 , wherein said plasticizer is selected from triethyl, tributyl, acetyl tributyl, acetyl triethyl, trioctyl, acetyl trioctyl, trihexyl citrate, dibutyl sebacate, triacetine, or derivatives thereof. 
     
     
         7 . The dosage form of  claim 1 , wherein said composition further comprises at least one penetration enhancer selected from benzalkonium chloride, cetylpyridinium chloride, cyclodextrins, dextran sulfate, lauric acid/propylene glycol, menthol, oleic acid, oleic acid derivatives, polyoxyethylene, polysorbates, sodium EDTA, sodium lauryl sulfate or sodium salicylate. 
     
     
         8 . An oral film dosage form comprising:
 at least one tadalafil in the form of particles; and   a polymer film matrix in which the tadalafil particles are dispersed, the polymer film matrix including (a) at least one crystallization inhibitor selected from polyvinyl pyrrolidone, polyethylene oxide and poloxamer in an amount that inhibits growth and agglomeration of the tadalafil particles, (b) from 15% to 19% by mass of the film dosage form of at least one substance that exists as a liquid at 37° C. and that enhances inhibition of growth and agglomeration of the tadalafil particles; and (c) at least one plasticizer in an amount that is effective to increase flexibility of the film dosage form.   
     
     
         9 . The dosage form of  claim 8 , wherein said plasticizer is selected from triethyl, tributyl, acetyl tributyl, acetyl triethyl, trioctyl, acetyl trioctyl, trihexyl citrate, dibutyl sebacate, triacetine, or derivatives thereof. 
     
     
         10 . The dosage form of  claim 8 , wherein said composition further comprises at least one penetration enhancer selected from benzalkonium chloride, cetylpyridinium chloride, cyclodextrins, dextran sulfate, lauric acid/propylene glycol, menthol, oleic acid, oleic acid derivatives, polyoxyethylene, polysorbates, sodium EDTA, sodium lauryl sulfate or sodium salicylate. 
     
     
         11 . The dosage form of  claim 8 , wherein the substance that enhances inhibition of growth and agglomeration of the active pharmaceutical particles is a polyoxyethylated glyceride. 
     
     
         12 . The dosage form of  claim 8 , wherein the active pharmaceutical ingredient is tadalafil. 
     
     
         13 . The dosage form of  claim 8 , in which the amount of the crystallization inhibitor is from about 25% to about 85% of the mass of the film dosage form. 
     
     
         14 . The dosage form of  claim 8 , in which the amount of the plasticizer is from about 2% to about 25% of the mass of the film dosage form. 
     
     
         15 . An oral film dosage form comprising:
 at least one active pharmaceutical in the form of particles; and   a polymer film matrix in which the active pharmaceutical particles are dispersed, the polymer film matrix including (a) at least one polymer that inhibits growth and agglomeration of the active pharmaceutical particles, (b) from 15% to 19% by mass of the film dosage form of at least one substance that exists as a liquid at 37° C. and that enhances inhibition of growth and agglomeration of the active pharmaceutical particles; and (c) at least one plasticizer in an amount that is effective to increase flexibility of the film dosage form.   
     
     
         16 . The dosage form of  claim 15 , wherein said plasticizer is selected from triethyl, tributyl, acetyl tributyl, acetyl triethyl, trioctyl, acetyl trioctyl, trihexyl citrate, dibutyl sebacate, triacetine, or derivatives thereof. 
     
     
         17 . The dosage form of  claim 15 , wherein said composition further comprises at least one penetration enhancer selected from benzalkonium chloride, cetylpyridinium chloride, cyclodextrins, dextran sulfate, lauric acid/propylene glycol, menthol, oleic acid, oleic acid derivatives, polyoxyethylene, polysorbates, sodium EDTA, sodium lauryl sulfate or sodium salicylate. 
     
     
         18 . The dosage form of  claim 15 , wherein the substance that enhances inhibition of growth and agglomeration of the active pharmaceutical particles is a polyoxyethylated glyceride. 
     
     
         19 . The dosage form of  claim 15 , wherein the active pharmaceutical ingredient is tadalafil. 
     
     
         20 . The dosage form of  claim 15 , in which the amount of the crystallization inhibitor is from about 25% to about 85% of the mass of the film dosage form.