Oral formulations of deferasirox

Abstract

Orally administerable deferasirox formulations are disclosed having reduced release under gastric conditions and fast release at near neutral pH or at neutral pH.

1 - 24 . (canceled) 
     
     
         25 . A tablet for oral administration which contains 90 mg deferasirox or a pharmaceutically acceptable salt thereof, wherein the tablet exhibits a disintegration time of 3-10 minutes when measured by a standard USP disintegration test; and,
 wherein the tablet further comprises,   (i) at least one filler in a total amount of about to 10% to 40% by weight based on total weight of the tablet;   (ii) at least one disintegrant in a total amount of about 1% to 10% by weight based on the total weight of the tablet;   (iii) at least one binder in a total amount of about 1% to 5% by weight based on the total weight of the tablet;   (iv) at least one surfactant in a total amount of about 0.0% to 2% by weight based on the total weight of the tablet;   (v) at least one glidant in a total amount of about 0.1% to 1% by weight based on the total weight of the tablet;   (vi) at least one lubricant in a total amount of less than about 0.1% to 2% by weight based on the total weight of the tablet; and   (vii) a coating.   
     
     
         26 . A tablet for oral administration according to  claim 25  wherein,
 (i) filler is selected from the group consisting essentially of microcrystalline cellulose, lactose, and ethylcellulose; 
 (ii) disintegrant is selected from the group consisting essentially of cross-linked polyvinylpyrrolidone (crospovidone), starch, CMC-Ca, CMC-Na, microcrystalline cellulose, alginic acid, sodium alginate, and guar gum; 
 (iii) binder is selected from the group consisting essentially of polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, microcrystalline cellulose, hypromellose, and starch; 
 (iv) surfactant is selected from the group consisting essentially of poloxamer, sodium laurel sulfate, betain, quaternary ammonium salt, polysorbate, and sorbitan ester; 
 (v) glidant is selected from the group consisting essentially of fumed silica, colloidal silicon dioxide, silica, colloidal silica, magnesium trisilicate, powdered cellulose, starch, and talc; and, 
 (vi) lubricant is selected from the group consisting essentially of magnesium stearate, Al-stearate, Ca-stearate, PEG 4000-8000, talc, sodium benzoate, glyceryl mono fatty acid, glyceryl monostearate, glyceryl dibehenate, glyceryl palmito-stearic ester, polyoxyethylene glycol, hydrogenated cotton seed oil, and castor seed oil. 
 
     
     
         27 . A tablet for oral administration according to  claim 25  wherein the tablet exhibits a disintegration time of 5-10 minutes. 
     
     
         28 . A tablet for oral administration according to  claim 26  wherein the tablet exhibits a disintegration time of 5-10 minutes. 
     
     
         29 . A tablet for oral administration which contains 180 mg deferasirox or a pharmaceutically acceptable salt thereof, wherein the tablet exhibits a disintegration time of 3-10 minutes when measured by a standard USP disintegration test; and,
 wherein the tablet further comprises,   (i) at least one filler in a total amount of about to 10% to 40% by weight based on total weight of the tablet;   (ii) at least one disintegrant in a total amount of about 1% to 10% by weight based on the total weight of the tablet;   (iii) at least one binder in a total amount of about 1% to 5% by weight based on the total weight of the tablet;   (iv) at least one surfactant in a total amount of about 0.0% to 2% by weight based on the total weight of the tablet;   (v) at least one glidant in a total amount of about 0.1% to 1% by weight based on the total weight of the tablet;   (vi) at least one lubricant in a total amount of less than about 0.1% to 2% by weight based on the total weight of the tablet; and   (vii) a coating.   
     
     
         30 . A tablet for oral administration according to  claim 29  wherein,
 (i) filler is selected from the group consisting essentially of microcrystalline cellulose, lactose, and ethylcellulose; 
 (ii) disintegrant is selected from the group consisting essentially of cross-linked polyvinylpyrrolidone (crospovidone), starch, CMC-Ca, CMC-Na, microcrystalline cellulose, alginic acid, sodium alginate, and guar gum; 
 (iii) binder is selected from the group consisting essentially of polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, microcrystalline cellulose, hypromellose, and starch; 
 (iv) surfactant is selected from the group consisting essentially of poloxamer, sodium laurel sulfate, betain, quaternary ammonium salt, polysorbate, and sorbitan ester; 
 (v) glidant is selected from the group consisting essentially of fumed silica, colloidal silicon dioxide, silica, colloidal silica, magnesium trisilicate, powdered cellulose, starch, and talc; and, 
 (vi) lubricant is selected from the group consisting essentially of magnesium stearate, Al-stearate, Ca-stearate, PEG 4000-8000, talc, sodium benzoate, glyceryl mono fatty acid, glyceryl monostearate, glyceryl dibehenate, glyceryl palmito-stearic ester, polyoxyethylene glycol, hydrogenated cotton seed oil, and castor seed oil. 
 
     
     
         31 . A tablet for oral administration according to  claim 29  wherein the tablet exhibits a disintegration time of 5-10 minutes. 
     
     
         32 . A tablet for oral administration according to  claim 30  wherein the tablet exhibits a disintegration time of 5-10 minutes. 
     
     
         33 . A tablet for oral administration which contains 360 mg deferasirox or a pharmaceutically acceptable salt thereof, wherein the tablet exhibits a disintegration time of 3-10 minutes when measured by a standard USP disintegration test; and,
 wherein the tablet further comprises,   (i) at least one filler in a total amount of about to 10% to 40% by weight based on total weight of the tablet;   (ii) at least one disintegrant in a total amount of about 1% to 10% by weight based on the total weight of the tablet;   (iii) at least one binder in a total amount of about 1% to 5% by weight based on the total weight of the tablet;   (iv) at least one surfactant in a total amount of about 0.0% to 2% by weight based on the total weight of the tablet;   (v) at least one glidant in a total amount of about 0.1% to 1% by weight based on the total weight of the tablet;   (vi) at least one lubricant in a total amount of less than about 0.1% to 2% by weight based on the total weight of the tablet; and   (vii) a coating.   
     
     
         34 . A tablet for oral administration according to  claim 33  wherein,
 (i) filler is selected from the group consisting essentially of microcrystalline cellulose, lactose, and ethylcellulose; 
 (ii) disintegrant is selected from the group consisting essentially of cross-linked polyvinylpyrrolidone (crospovidone), starch, CMC-Ca, CMC-Na, microcrystalline cellulose, alginic acid, sodium alginate, and guar gum; 
 (iii) binder is selected from the group consisting essentially of polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, microcrystalline cellulose, hypromellose, and starch; 
 (iv) surfactant is selected from the group consisting essentially of poloxamer, sodium laurel sulfate, betain, quaternary ammonium salt, polysorbate, and sorbitan ester; 
 (v) glidant is selected from the group consisting essentially of fumed silica, colloidal silicon dioxide, silica, colloidal silica, magnesium trisilicate, powdered cellulose, starch, and talc; and, 
 (vi) lubricant is selected from the group consisting essentially of magnesium stearate, Al-stearate, Ca-stearate, PEG 4000-8000, talc, sodium benzoate, glyceryl mono fatty acid, glyceryl monostearate, glyceryl dibehenate, glyceryl palmito-stearic ester, polyoxyethylene glycol, hydrogenated cotton seed oil, and castor seed oil. 
 
     
     
         35 . A tablet for oral administration according to  claim 33  wherein the tablet exhibits a disintegration time of 5-10 minutes. 
     
     
         36 . A tablet for oral administration according to  claim 34  wherein the tablet exhibits a disintegration time of 5-10 minutes.