Sustained-release tablet composition of pramipexole

• US 8,399,016 B2
• Filed: 03/03/2010
• Issued: 03/19/2013
• Est. Priority Date: 07/25/2002
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Amidon, Gregory Everett, Ganorkar, Loksidh Devi, Heimlich, John Mark, Lee, Ernest J., Noack, Robert Martin, Reo, Joseph Peter, Skoug, Connie Jo
• Primary Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US12/716,755
• Publication Number:
  US 20100316710A1
• Time in Patent Office: 1,112 Days
• Field of Search: None
• US Class Current: 424/468
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A sustained-release pharmaceutical composition in a form of an orally deliverable tablet comprises a water-soluble salt of pramipexole, dispersed in a matrix comprising a hydrophilic polymer and a starch having a tensile strength of at least about 0.15 kN cm⁻² at a solid fraction representative of the tablet.

Claims

1. A pharmaceutical composition in a form of an orally deliverable, sustained-release tablet having a core comprising pramipexole dihydrochloride monohydrate in an amount of about 0.375, 0.75, 1.5, 3 or 4.5 mg, dispersed in a matrix comprising (a) hydroxypropylmethylcellulose in an amount of about 35% to about 50% by weight of the tablet and (b) a pregelatinized starch having a tensile strength of at least about 0.15 kN cm⁻

2 at a solid fraction of 0.8 as measured using a compact consisting only of said starch, in an amount of about 45% to about 65% by weight of the tablet;

said core being substantially enclosed in a coating that constitutes about 2% to about 7% of the weight of the tablet, said coating comprising an ethylcellulose-based hydrophobic or water-insoluble component and an HPMC-based pore-forming component in an amount of about 10% to about 40% by weight of the ethylcellulose-based component, further wherein said tablet provides sustained release as compared with an immediate release pramipexole formulation.

2. The composition of claim 1 wherein the starch has a tensile strength of at least about 0.175 kN cm⁻

2.

3. The composition of claim 1 wherein the starch has a tensile strength of at least about 0.2 kN cm⁻

2.

4. A method of treatment of a subject having a condition or disorder for which a dopamine D2 receptor agonist is indicated, the method comprising orally administering not more than once daily to the subject the pharmaceutical composition of claim 1.

5. The method of claim 4 wherein the condition or disorder is Parkinson'"'"'s disease or a complication associated therewith.

6. The composition of claim 1, wherein said composition, when administered once daily, exhibits a bioavailability substantially equivalent to an equal daily dose of an immediate-release pramipexole dihydrochloride reference formulation administered three times a day.