Immediate release dosage forms containing solid drug dispersions

Abstract

High loading immediate release dosage forms containing at least 30 wt % of a solid drug dispersion, at least 5 wt % of a disintegrant and a porosigen are disclosed that exhibit excellent strength and aqueous solubility.

1 . A high loading immediate release dosage form comprising: 
 (a) at least 30 wt % of a solid dispersion formed by spray-drying, said dispersion comprising a low solubility drug and a concentration-enhancing polymer, said polymer being present in said dispersion in an amount sufficient to provide enhancement of the concentration of said drug in a use environment relative to a control composition consisting essentially of an equivalent amount of said drug alone;    (b) at least 5 wt % of a disintegrant; and    (c) a porosigen    wherein said dosage form disintegrates in 10 minutes or less following introduction to a disintegration medium.    
     
     
         2 . A high loading immediate release dosage form comprising: 
 (a) at least 30 wt % of a solid dispersion formed by spray-drying, said dispersion comprising a low solubility drug and a concentration-enhancing polymer, said polymer being present in said dispersion in an amount sufficient to provide enhancement of the concentration of said drug in a use environment relative to a control composition consisting essentially of an equivalent amount of said drug alone;    (b) at least 5 wt % of a disintegrant; and    (c) a porosigen    wherein said dosage form releases at least 70% of said drug within 15 minutes following introduction to a dissolution medium.    
     
     
         3 . A high loading immediate release dosage form comprising: 
 (a) at least 50 wt % of a solid dispersion, said dispersion comprising a low solubility drug and a concentration-enhancing polymer, said polymer being present in said dispersion in an amount sufficient to provide enhancement of the concentration of said drug in a use environment relative to a control composition consisting essentially of an equivalent amount of said drug alone;    (b) at least 5 wt % of a disintegrant; and    (c) a porosigen    wherein said dosage form disintegrates in 10 minutes or less following introduction to a disintegration medium.    
     
     
         4 . A high loading immediate release dosage form comprising: 
 (a) at least 50 wt % of a solid dispersion, said dispersion comprising a low solubility drug and a concentration-enhancing polymer, said polymer being present in said dispersion in an amount sufficient to provide enhancement of the concentration of said drug in a use environment relative to a control composition consisting essentially of an equivalent amount of said drug alone;    (b) at least 5 wt % of a disintegrant; and    (c) a porosigen    wherein said dosage form releases at least 70% of said drug within 15 minutes following introduction to a dissolution medium.    
     
     
         5 . The dosage form of any of claims  1 - 4  wherein said porosigen is present in an amount of at least 10 wt %.  
     
     
         6 . The dosage form of any of claims  1 - 4  wherein said disintegrant provides a swelling energy of at least about 0.05 J/g within about 10 minutes after introduction to an environment of use.  
     
     
         7 . The dosage form of  claim 1  or  2  wherein said solid dispersion is present in an amount of at least 50 wt %.  
     
     
         8 . The dosage form of any of claims  1 - 4  wherein said dosage form provides a maximum concentration of said drug in said use environment that is at least 1.25-fold the equilibrium concentration of said drug provided by said control composition.  
     
     
         9 . The dosage form of any of claims  1 - 4  wherein said dosage form provides in said use environment an area under the concentration versus time curve for any period of at least 90 minutes between the time of introduction into said use environment and about 270 minutes following introduction to said use environment that is at least about 1.25-fold that of said control composition.  
     
     
         10 . The dosage form of any of claims  1 - 4  wherein said dosage form provides a relative bioavailability that is at least 1.25-fold that of said control composition.  
     
     
         11 . The dosage form of any of claims  1 - 4  wherein said concentration-enhancing polymer is selected from the group consisting of hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxymethyl ethyl cellulose, hydroxypropyl methyl cellulose acetate succinate, hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, polyvinyl alcohols that have at least a portion of their repeat units in hydrolyzed form, polyvinyl pyrrolidone, poloxamers and blends thereof.  
     
     
         12 . The dosage form of any of claims  1 - 4  wherein said drug is selected from the group consisting of antihypertensives, antianxiety agents, anticlotting agents, anticonvulsants, blood glucose-lowering agents, decongestants, antihistamines, antitussives, antineoplastics, beta blockers, anti-inflammatories, antipsychotic agents, cognitive enhancers, anti-atherosclerotic agents, cholesterol-reducing agents, antiobesity agents, autoimmune disorder agents, anti-impotence agents, antibacterial and antifungal agents, hypnotic agents, anti-Parkinsonism agents, anti-Alzheimer's disease agents, antibiotics, anti-depressants, antiviral agents, glycogen phosphorylase inhibitors, and cholesterol ester transfer protein inhibitors.  
     
     
         13 . The dosage form of any of claims  1 - 4  wherein said drug is selected from the group consisting of [2R,4S]-4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, [2R,4S]-4-[3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester and [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester.  
     
     
         14 . A method of treating an animal in need of treatment by a drug, comprising administering to said animal the dosage form of any of claims  1 - 4  containing an effective amount of an appropriate therapeutic drug.