Delayed release cysteamine bead formulation, and methods of making and using same

Abstract

An enteric-coated bead dosage form of cysteamine, and related methods of manufacture and use, are disclosed.

1 - 20 . (canceled) 
     
     
         21 . A pharmaceutical delayed-release dosage form comprising enterically-coated beads comprising cysteamine bitartrate, or cystamine or pharmaceutically-acceptable salts thereof, or a combination thereof, wherein the coating does not release more than 10 wt. % of the cysteamine bitartrate or cystamine after 2 hours in 0.1N HCl at 22° C. 
     
     
         22 . The pharmaceutical delayed-release dosage form of  claim 21 , wherein the coating releases at least 80 wt. % of the cysteamine bitartrate, cystamine or pharmaceutically-acceptable salts thereof, or a combination thereof, after 20 minutes at pH 6.8. 
     
     
         23 . The pharmaceutical delayed-released dosage form of  claim 22 , wherein the release is measured using the method of USP 36-NF 31 section 711. 
     
     
         24 . The pharmaceutical delayed-release dosage form of  claim 21 , wherein the coating is between about 25% to about 31% as measured by weight gain compared to uncoated beads. 
     
     
         25 . The pharmaceutical delayed-release dosage form of  claim 21 , wherein the beads range from 0.84 mm to about 1.68 mm. 
     
     
         26 . The pharmaceutical delayed-release dosage form of  claim 25 , wherein the beads can be sieved such that 5% or less of the particles by weight are retained on a #12 mesh screen and 10% or less by weight pass through a #20 mesh screen. 
     
     
         27 . The pharmaceutical delayed-release dosage form of  claim 26 , wherein about 13% to about 16% of the beads are retained by a 850 μm sieve, about 19% to about 27% are retained by a 1180 μm sieve, about 56% to about 62% are retained by a 1000 μm sieve, and about 1% to about 3% are retained by a 1400 μm sieve. 
     
     
         28 . The pharmaceutical delayed-released dosage form of  claim 21 , wherein the dosage form is characterized by having less than 5 wt. % cystamine based on the amount of cysteamine. 
     
     
         29 . The pharmaceutical delayed-released dosage form of  claim 28 , wherein the dosage form is characterized by having less than 5 wt. % cystamine based on the amount of cysteamine, following 18 months storage at 25° C., and 40% RH. 
     
     
         30 . A method of treating a subject with cystinosis comprising administering a composition of  claim 21 . 
     
     
         31 . The method of  claim 30 , wherein each administration comprises an amount of cysteamine bitartrate that would yield a dose of 100 to 1000 mg cysteamine free base. 
     
     
         32 . The method according to  claim 31 , wherein the total daily dose of cysteamine free base is up to about 2 g/m 2  body surface area. 
     
     
         33 . A method of preparing the composition of  claim 21 , comprising coating beads of cysteamine bitartrate, cystamine or pharmaceutically-acceptable salts thereof, or a combination thereof, and an excipient with an enteric polymer to form an enteric coating, wherein the coating does not release more than 10 wt. % of the cysteamine bitartrate or cystamine after 2 hours in 0.1N HCl at 22° C. 
     
     
         34 . The method of  claim 33 , wherein the coating is between about 25% to about 31% as measured by weight gain compared to uncoated beads. 
     
     
         35 . The method of  claim 33 , wherein the enterically-coated beads range from 0.84 mm to about 1.68 mm. 
     
     
         36 . The method of  claim 35 , wherein the beads can be sieved such that 5% or less of the particles by weight are retained on a #12 mesh screen and 10% or less by weight pass through a #20 mesh screen. 
     
     
         37 . The method of  claim 36 , wherein about 13% to about 16% of the beads are retained by a 850 μm sieve, about 19% to about 27% are retained by a 1180 μm sieve, about 56% to about 62% are retained by a 1000 μm sieve, and about 1% to about 3% are retained by a 1400 μm sieve. 
     
     
         38 . The method of  claim 33 , wherein the composition is characterized by having less than 5 wt. % cystamine free base based on the amount of cysteamine free base, following 18 months storage at 25° C., and 40% RH.