Compositions and Methods for Treating Metabolic Disorders
OwnerAlain D. BARON, Mark S. FINEMAN +2inventors
InventorsAlain D. BARON, Mark S. FINEMAN, Terri KIM, Stephen Kwaku DORDUNOO
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Abstract
Compositions and methods for improving the pharmacokinetics and reducing the risk of adverse events resulting from biguanide compound administration are provided, comprising administering delayed release formulations of such compounds having a lag phase release.
Claims33
A delayed-release pharmaceutical composition for biguanide compound delivery, comprising an oral dosage form having a core comprising a therapeutically effective amount of a biguanide compound and an enteric coating surrounding said core that delays release of said biguanide compound after ingestion until reaching the distal small intestine, and further minimizes the release of said biguanide compound from said oral dosage form for a lag phase of at least about ten minutes after contacting a pH of at least about 6.0.
The pharmaceutical composition according to any one of the preceding claims, wherein said oral dosage form releases less than about 10% or 5% of the therapeutically effective amount of said biguanide compound after contacting an aqueous medium at a pH of less than about 2 for two hours, followed by contacting an aqueous medium at a pH equal to or less than about 5.5 for 30 to 45 minutes.
The pharmaceutical composition according to any one of the preceding claims, wherein said oral dosage form releases less than about 15%, 10%, or 5% of the therapeutically effective amount of said biguanide compound during said lag phase.
The pharmaceutical composition according to any one of the preceding claims, wherein said oral dosage form releases between about 75% to about 100% of the therapeutically effective amount of said biguanide compound within about 90 minutes after contacting a pH of about 6.8.
The pharmaceutical composition according to any one of the preceding claims, wherein said enteric coating comprises a polymer that is insoluble in acidic media, but dissolves above pH 7.0.
The pharmaceutical composition according to any one of the preceding claims, wherein said enteric coating further comprises a polymer that is insoluble at pH 5.5 and below, but dissolves above pH 5.5.
The pharmaceutical composition according to any one of the preceding claims, further comprising a seal coating between the core and the enteric coating, providing a total coating thickness of at least about 4% to 7% (wt./wt.) weight gain, more preferably at least about a 4.5% to 6% (wt./wt.) weight gain.
The pharmaceutical composition according to claim 16 or 17, wherein the seal coating comprises hypromellose, titanium dioxide, polyethylene glycol 400, polysorbate 80, triacetin, talc, and combinations thereof.
The pharmaceutical composition according to any one of the preceding claims, wherein said biguanide compound is selected from the group consisting of metformin, phenformin, buformin and imeglimin.
The pharmaceutical composition according to any of the preceding claims, where said oral dosage form comprises an enterically-coated tablet, capsule or microsphere.
Dependencies are inferred from the claim text.