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

1. 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;

wherein the enteric membrane begins to dissolve within a pH range of about 4.5 to about 6.5;

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; and

wherein the pharmaceutical dosage form, upon administration in a capsule to fasted healthy normal subjects at 600 mg free cysteamine base, provides:

(a) a mean Cmax upon oral dosing in a range of 2.3±0.6 mg/L or in a range of 80% to 125% thereof; and

(b) a mean AUC (0-inf_D) upon oral dosing in a range of 0.84±0.19 min*mg/L/mg or in a range of 80% to 125% thereof.

2. The pharmaceutical dosage form of claim 1 , wherein the cysteamine (as free base) comprises at least 10 wt. % of the core particle.

3. The pharmaceutical dosage form of claim 1 , wherein the cysteamine or pharmaceutically acceptable salt thereof is cysteamine bitartrate.

4. The pharmaceutical dosage form of claim 3 , wherein the cysteamine bitartrate comprises at least 50 wt. % of the core particle.

5. The pharmaceutical dosage form of claim 1 , wherein the beads provide a mean Cmax and mean AUC (0-inf_D) upon oral dosing, fasted, when administered inside a capsule shell that are bioequivalent to the mean Cmax and mean AUC (0-inf_D) upon oral dosing, fasted, when administered without a capsule shell.

6. The pharmaceutical dosage form of claim 1 , wherein the enteric membrane comprises an enteric material that begins to dissolve at pH of about 5.5 in an aqueous solution.

7. The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form, upon administration in a capsule to fasted healthy normal subjects at 600 mg free cysteamine base, provides:

(a) a mean Cmax upon oral dosing in a range of 2.3±0.6 mg/L; and

(b) a mean AUC (0-inf_D) upon oral dosing in a range of 0.84±0.19 min*mg/L/mg.

8. The pharmaceutical dosage form of claim 1 , wherein the pharmaceutical dosage form, upon administration in a capsule to fasted healthy normal subjects at 600 mg free cysteamine base, provides:

(a) a mean Cmax upon oral dosing of 2.3 mg/L or in a range of 80% to 125% thereof; and

(b) a mean AUC (0-inf_D) upon oral dosing of 0.84 min*mg/L/mg or in a range of 80% to 125% thereof.