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.

What is claimed is: 
     
         1 .- 48 . (canceled) 
     
     
         49 . A pharmaceutical dosage form comprising delayed-release cysteamine beads, the beads comprising: (i) a core particle comprising a mixture of cysteamine, or a pharmaceutically acceptable salt thereof, and a binder, and (ii) an enteric membrane surrounding the core particle; wherein the beads have a distribution of particle sizes in a range of about 0.7 mm to about 2.8 mm and wherein the pharmaceutical dosage form is characterized by having less than 5 wt. % cystamine, based on the amount of cysteamine, following storage at 25° C. and 60% relative humidity for 6 months, as determined by reverse phase HPLC with UV detection at 210 nm. 
     
     
         50 . The pharmaceutical dosage form of  claim 49 , wherein the pharmaceutical dosage form is characterized by having less than 5 wt. % cystamine, based on the amount of cysteamine, following storage at 25° C. and 60% relative humidity for 12 months, as determined by reverse phase HPLC with UV detection at 210 nm. 
     
     
         51 . The pharmaceutical dosage form of  claim 50 , wherein the pharmaceutical dosage form is characterized by having less than 5 wt. % cystamine, based on the amount of cysteamine, following storage at 25° C. and 60% relative humidity for 18 months, as determined by reverse phase HPLC with UV detection at 210 nm. 
     
     
         52 . The pharmaceutical dosage form of  claim 51 , wherein the pharmaceutical dosage form is characterized by having less than 5 wt. % cystamine, based on the amount of cysteamine, following storage at 25° C. and 60% relative humidity for 24 months, as determined by reverse phase HPLC with UV detection at 210 nm. 
     
     
         53 . The pharmaceutical dosage form of  claim 49 , further characterized by having less than 8 wt. % total related substances (impurities) based on the amount of cysteamine, under the described storage conditions and times, as determined by reverse phase HPLC with UV detection at 210 nm. 
     
     
         54 . The pharmaceutical dosage form of  claim 49 , wherein the binder comprises microcrystalline cellulose. 
     
     
         55 . The pharmaceutical dosage form of  claim 49 , wherein the binder comprises hypromellose. 
     
     
         56 . The pharmaceutical dosage form of  claim 49 , wherein the enteric membrane is present in an amount in a range of about 20% to about 40% by weight, based on the weight of the core particles. 
     
     
         57 . The pharmaceutical dosage form of  claim 49 , wherein the enteric membrane is present in an amount in a range of about 25% to about 35% by weight, based on the weight of the core particles. 
     
     
         58 . The pharmaceutical dosage form of  claim 49 , wherein the cysteamine (as free base) is present in the bead core particle in an amount of at least 10 wt. %. 
     
     
         59 . The pharmaceutical dosage form of  claim 49 , wherein the cysteamine or pharmaceutically acceptable salt thereof is a pharmaceutically acceptable salt of cysteamine. 
     
     
         60 . The pharmaceutical dosage form of  claim 59 , wherein the pharmaceutically acceptable salt of cysteamine is cysteamine bitartrate. 
     
     
         61 . The pharmaceutical dosage form of  claim 49 , further comprising a capsule shell enclosing the beads. 
     
     
         62 . A pharmaceutical dosage form comprising delayed-release cysteamine beads, the beads comprising: (i) a core particle comprising a mixture of cysteamine bitartrate and a binder, and (ii) an enteric membrane surrounding the core particle; wherein the beads have a distribution of particle sizes in a range of about 0.7 mm to about 2.8 mm and wherein the pharmaceutical dosage form is characterized by having less than 5 wt. % cystamine, based on the amount of cysteamine, following storage at 40° C. and 75% relative humidity for 3 months, as determined by reverse phase HPLC with UV detection at 210 nm. 
     
     
         63 . The pharmaceutical dosage form of  claim 62 , wherein the pharmaceutical dosage form is characterized by having less than 5 wt. % cystamine, based on the amount of cysteamine, following storage at 40° C. and 75% relative humidity for 6 months, as determined by reverse phase HPLC with UV detection at 210 nm. 
     
     
         64 . The pharmaceutical dosage form of  claim 62 , further characterized by having less than 8 wt. % total related substances (impurities) based on the amount of cysteamine, under the described storage conditions and times, as determined by reverse phase HPLC with UV detection at 210 nm. 
     
     
         65 . The pharmaceutical dosage form of  claim 62 , wherein the binder comprises microcrystalline cellulose. 
     
     
         66 . The pharmaceutical dosage form of  claim 62 , wherein the binder comprises hypromellose. 
     
     
         67 . The pharmaceutical dosage form of  claim 62 , wherein the enteric membrane is present in an amount in a range of about 20% to about 40% by weight, based on the weight of the core particles. 
     
     
         68 . The pharmaceutical dosage form of  claim 62 , wherein the enteric membrane is present in an amount in a range of about 25% to about 35% by weight, based on the weight of the core particles. 
     
     
         69 . The pharmaceutical dosage form of  claim 62 , wherein the cysteamine (as free base) is present in the bead core particle in an amount of at least 10 wt. %. 
     
     
         70 . The pharmaceutical dosage form of  claim 62 , wherein the cysteamine or pharmaceutically acceptable salt thereof is a pharmaceutically acceptable salt of cysteamine. 
     
     
         71 . The pharmaceutical dosage form of  claim 70 , wherein the pharmaceutically acceptable salt of cysteamine is cysteamine bitartrate. 
     
     
         72 . The pharmaceutical dosage form of  claim 62 , further comprising a capsule shell enclosing the beads.