Delayed Release Cysteamine Bead Formulation, And Methods Of Making And Using Same
An enteric-coated bead dosage form of cysteamine, and related methods of manufacture and use, are disclosed.
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.