|Title:||Sustained-release tablet composition of pramipexole|
|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.sup.-2 at a solid fraction representative of the tablet.|
|Inventor(s):||Amidon; Gregory Everett (Portage, MI), Ganorkar; Loksidh Devi (Kalamazoo, MI), Heimlich; John Mark (Portage, MI), Lee; Ernest J. (Kalamazoo, MI), Noack; Robert Martin (Ann Arbor, MI), Reo; Joseph Peter (Kalamazoo, MI), Skoug; Connie Jo (Portage, MI)|
|Assignee:||Boehringer Ingelheim International GmbH (Ingelheim am Rhein, DE)|
|Filing Date:||Mar 03, 2010|
|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.sup.-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.sup.-2.
3. The composition of claim 1 wherein the starch has a tensile strength of at least about 0.2 kN cm.sup.-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.