Pharmaceutical dosage form with multiple coatings for reduced impact of coating fractures

Abstract

The present invention relates to a pharmaceutical composition in a solid unit dosage form for oral administration in a human or lower animal comprising: a. a safe and effective amount of a therapeutically active agent; b. an inner coating layer selected from the group consisting of poly(methacrylic acid, methyl methacrylate) 1:2, poly(methacrylic acid, methyl methacrylate) 1:1, and mixtures thereof; and c. an outer coating layer comprising an enteric polymer or film coating material; wherein the inner coating layer is not the same as the outer coating layer; wherein if the inner coating layer is poly(methacrylic acid, methyl methacrylate) 1:1 then the outer coating layer is not poly(methacrylic acid, methyl methacrylate) 1:2 or is not a mixture of poly(methacrylic acid, methyl methacrylate) 1:1 and poly(methacrylic acid, methyl methacrylate) 1:2; and wherein the inner coating layer and the outer coating layer do not contain any therapeutically active agent. This invention further relates to a method of maintaining the desired site of delivery of a therapeutic agent in the gastrointestinal tract by administering the above compositions to a human or lower animal.

1 - 24 . (canceled)  
     
     
         25 . A pharmaceutical composition in a solid unit dosage form for oral administration in a human or lower animal comprising: 
 a. a safe and effective amount of a therapeutically active agent;    b. an inner coating layer selected from the group consisting of poly(methacrylic acid, methyl methacrylate) 1:2, poly(methacrylic acid, methyl methacrylate) 1:1, and mixtures thereof; and    c. an outer coating layer having a minimum thickness from about 10 μm to about 200 μm, applied to the inner coating layer, said outer coating layer comprising a film coating material selected from the group consisting of cellulose ethers, methyl cellulose, ethylcellulose, carboxymethylcellulose, carboxymethylethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, low viscosity hydroxypropyl cellulose, low viscosity hydroxypropyl methylcellulose, wax, carnauba wax, fatty alcohols, hydrogenated vegetable oils, zein, shellac, sucrose, Arabic gum, polyethylene glycol, polyvinylpyrolidone, gelatin, sodium alginate, dextrin, psyllium husk powder, cellulose acetate phthalate, cellulose acetate trimelliate, hydroxypropyl methylcellulose phthalate (HPMCP), cellulose propionate phthalate, cellulose acetate maleate, polyvinyl alcohol phthalate, hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose hexahydrophthalate, and compatible mixtures thereof;    wherein the solid unit dosage form has a total weight from about 550 mg to about 1500 mg; and    wherein the inner coating layer and the outer coating layer contain no therapeutically active agent.    
     
     
         26 . The composition of  claim 25  wherein the inner coating layer is poly(methacrylic acid, methyl methacrylate) 1:2.  
     
     
         27 . The composition of  claim 25  wherein the film coating material is selected from the group consisting of cellulose ethers, methyl cellulose, ethylcellulose, carboxymethylcellulose, carboxymethylethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, low viscosity hydroxypropyl cellulose, low viscosity hydroxypropyl methylcellulose, wax, carnauba wax, Arabic gum, polyethylene glycol, polyvinylpyrolidone, cellulose acetate phthalate, cellulose acetate trimelliate, hydroxypropyl methylcellulose phthalate (HPMCP), cellulose propionate phthalate, cellulose acetate maleate, polyvinyl alcohol phthalate, hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose hexahydrophthalate, and compatible mixtures thereof.  
     
     
         28 . The composition of  claim 27  wherein the film coating material is selected from the group consisting of cellulose ethers, methyl cellulose, ethylcellulose, carboxymethylcellulose, carboxymethylethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and compatible mixtures thereof.  
     
     
         29 . The composition of  claim 28  wherein the film coating material is a mixture of hydroxypropyl cellulose and hydroxypropyl methylcellulose.  
     
     
         30 . The composition of  claim 25  wherein the therapeutically active agent is selected from the group consisting of laxatives, anti-diarrheals, nonsteroidal anti-inflammatory agents, glucocorticoids, antimicrobials, immunosuppressants, chemotherapeutics or anti-cancer drugs, peptides, proteins, cardiovascular drugs, psychotropic drugs, H2-blockers, antiasthmatic agents, and antihistamines.  
     
     
         31 . The composition of  claim 30  wherein the therapeutically active agent is a nonsteroidal anti-inflammatory agent.  
     
     
         32 . The composition of  claim 31  wherein the nonsteroidal anti-inflammatory agent is 5-amino salicylic acid or a pharmaceutically acceptable salt or ester thereof.  
     
     
         33 . The composition of  claim 32  wherein the 5-amino salicylic acid or pharmaceutically acceptable salt or ester thereof is present in an amount from about 700 mg to about 900 mg per solid unit dosage form.  
     
     
         34 . The composition of  claim 25  wherein the outer coating layer has a minimum thickness from about 30 μm to about 150 μm.  
     
     
         35 . The composition of  claim 25  wherein the total coating thickness of the inner and outer coating layers combined is from about 5 mg/cm 2  to about 40 mg/cm 2 .  
     
     
         36 . The composition of  claim 35  wherein the total coating thickness is from about 10 mg/cm 2  to about 15 mg/cm 2 .  
     
     
         37 . The composition of  claim 25  wherein the solid dosage form is coated by continuous spray methods wherein the outer coating layer is applied after the inner coating layer but before the inner coating layer is dried or cured.  
     
     
         38 . The composition of  claim 25  wherein the solid unit dosage form has a total weight from about 600 mg to about 1200 mg.  
     
     
         39 . The composition of  claim 38  wherein the solid unit dosage form has a total weight from about 750 mg to about 1000 mg.  
     
     
         40 . The composition of  claim 25  wherein the solid dosage form is a compressed tablet.  
     
     
         41 . A method of consistent and reliable delivery and release of a therapeutically active agent to the desired region of delivery by orally administering the composition of  claim 25 .  
     
     
         42 . A pharmaceutical composition in a solid unit dosage form for oral administration in a human or lower animal comprising: 
 a. a safe and effective amount of 5-amino salicylic acid;    b. an inner coating layer comprising poly(methacrylic acid, methyl methacrylate) 1:2; and    c. an outer coating layer having a minimum thickness from about 10 μm to about 200 μm, applied to the inner coating layer, said outer coating layer comprising a mixture of hydroxypropyl cellulose and hydroxypropyl methylcellulose.    
     
     
         43 . A method of consistent and reliable delivery and release of 5-amino salicylic acid to the desired region of delivery by orally administering the composition of  claim 42.