Sustained Release Particulate Oral Dosage Forms of (R)-Baclofen and Methods of Treatment
AssigneeXenoPort, Inc.
InventorsSrikonda SASTRY, Kenneth CUNDY, Manshiu LEUNG
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Abstract
Sustained release particulate oral dosage forms of (R)-baclofen prodrugs and methods of treating a disease comprising orally administering such dosage forms are disclosed.
Claims23
An oral pharmaceutical dosage form of an (R)-baclofen prodrug, comprising:
- a combination of at least two particle populations, wherein at least one of the two particle populations is chosen from (a) and (b):
- (a) a population of (R)-baclofen prodrug-containing particles, the particles when placed in an aqueous solution releasing the (R)-baclofen prodrug into the solution with a release profile that is independent of the solution pH;
- and
- (b) a population of (R)-baclofen prodrug-containing particles, the particles when placed in an aqueous solution releasing the (R)-baclofen prodrug into the solution with a release profile that is dependent on the solution pH;
- wherein the oral dosage form provides a therapeutically effective concentration of (R)-baclofen in plasma of a patient for a continuous period of time after the oral dosage form is orally administered to the patient.
An oral pharmaceutical dosage form of (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of any of the foregoing, which when administered orally to a patient provides a therapeutically effective concentration of (R)-baclofen in the plasma of the patient for a continuous period of time after the dosage form is orally administered to the patient, wherein the concentration of (R)-baclofen in the plasma of the patient does not exceed a minimum adverse concentration at any time after the dosage form is orally administered to the patient.
An oral dosage form comprising a plurality of pH-independent release particles comprising a (R)-baclofen prodrug of Formula (I), which following oral administration to a human patient provides a blood (R)-3-amino-3-(4-chlorophenyl)butanoic acid concentration characterized by:
- a Cmax/C12 ratio ranging from about 1 to about 6;
- a Cmax/dose ratio ranging from about 1.25 (106·mL)−1 to about 3.25 (106·mL)−1;
- and
- an AUCinf/dose ratio ranging from about 13 (hr/106·mL) to about 33 (hr/106·mL).
Dependencies are inferred from the claim text.