Extended release compositions comprising trihexyphenidyl

A pharmaceutical pellet composition comprising:

• a) a core comprising an organic acid;
• b) a first drug layer encompassing at least a portion of the core, wherein the first drug layer comprises trihexyphenidyl or a pharmaceutically acceptable salt thereof;
• and
• c) a functional coat encompassing at least a portion of the drug layer,
• wherein the functional coat comprises a nonionic water-insoluble polymer and a pore former,
• wherein the composition provides extended release of trihexyphenidyl a pharmaceutically acceptable salt thereof, with a Cmin:Cmax ratio of ≥0.4, for a period of at least 12 hours, and
• wherein the composition improves solubility of trihexyphenidyl or a pharmaceutically acceptable salt thereof at a pH of greater than or equal to 5 to maintain a therapeutic plasma concentration of trihexyphenidyl or a pharmaceutically acceptable salt thereof for at least about 12 hours.

A therapeutic method for treating dystonia, sialorrhea, or dyskinesia, the method comprising orally administering to a subject in need thereof an extended release trihexyphenidyl composition comprising:

• a) a core comprising an organic acid;
• b) a drug layer encompassing at least a portion of the core, wherein the drug layer comprises trihexyphenidyl or a pharmaceutically acceptable salt thereof;
• and
• c) a functional coat encompassing at least a portion of the drug layer, wherein the functional coat comprises a nonionic water-insoluble polymer and a pore former,
• wherein the composition is for oral administration,
• wherein the composition provides extended release of trihexyphenidyl or a pharmaceutically acceptable salt thereof, with a Cmin:Cmax ratio of ≥0.4, for a period of at least about 12 hours, and
• wherein the composition improves solubility of trihexyphenidyl or a pharmaceutically acceptable salt thereof at a pH of greater than or equal to about 5 to maintain a therapeutic concentration of trihexyphenidyl or a pharmaceutically acceptable salt thereof for at least about 12 hours.

A method for improving patient compliance, the method comprising orally administering to a patient in need thereof, an extended release trihexyphenidyl composition comprising,

• a) a core comprising an organic acid;
• b) a drug layer encompassing at least a portion of the core, wherein the drug layer comprises trihexyphenidyl or a pharmaceutically acceptable salt thereof;
• and
• c) a functional coat encompassing at least a portion of the drug layer,
• wherein the functional coat comprises a nonionic water-insoluble polymer and a pore former,
• wherein the composition improves solubility of trihexyphenidyl or a pharmaceutically acceptable salt thereof at a pH of greater than or equal to about 5 to maintain a therapeutically effective concentration of trihexyphenidyl or a pharmaceutically acceptable salt thereof, for a period of at least about 12 hours, and
• wherein the composition reduces side effects associated with high peak serum concentration (Cmax) and low trough-to-peak concentration ratios (Cmin:Cmax) of <0.4.

A method of making a pharmaceutical pellet composition comprising trihexyphenidyl or a pharmaceutically acceptable salt thereof, the method comprising:

• coating a core comprising an organic acid with a drug layer comprising trihexyphenidyl or a pharmaceutically acceptable salt thereof to obtain a drug layered core, and coating the drug layered core with a functional coat comprising a nonionic water-insoluble polymer and a pore former,
• wherein, the nonionic water-insoluble polymer is selected from the group consisting of ethyl cellulose, cellulose acetate, a polyvinyl acetate dispersion, and combinations thereof;
• wherein the pore former is a nonionic water-soluble polymer, an enteric polymer, or a plasticizer;
• and
• wherein the core consists of one or more organic acids, or is a nonpareil seed coated with an organic acid layer.