Solid oral dosage form comprising a combination of metformin and glibenclamide

A solid pharmaceutical composition comprising metformin and glibenclamide in particulate form, wherein the size of the glibenclamide particles is such that at most 10% of the particles are less than 2 μm and at most 10% of the particles are greater than 60 μm.

A solid oral dosage form comprising a combination of metformin and glibenclamide in which the size of glibenclamide is such that at most 25% of the particles are less than 11 μm and at most 25% of the particles are greater than 46 μm.

A pharmaceutical composition comprising a single solid oral dosage form containing an effective dose of metformin and an effective dose of glibenclamide wherein, after oral administration thereof to a human, the bioavailability of glibenclamide is comparable to the bioavailability of glibenclamide achieved by oral administration of separate solid oral dosage forms to a human, one containing glibenclamide and the other metformin, in the same respective effective doses as in said single oral dosage form.

A pharmaceutical composition comprising a single solid oral dosage form containing an effective dose of metformin and an effective dose of glibenclamide wherein, after oral administration thereof to a human, the Cmax and AUC of glibenclamide are comparable to the Cmax and AUC of glibenclamide achieved by oral administration of separate solid oral dosage forms to a human, one containing glibenclamide and the other metformin, in the same respective effective doses as in said single oral dosage form.

A pharmaceutical composition comprising a single solid oral dosage form containing an effective dose of metformin and an effective dose of glibenclamide wherein, after oral administration thereof to a human, the Cmax and AUC of glibenclamide are ±25% of the Cmax and AUC, respectively, of the glibenclamide achieved by oral administration to a human of separate solid oral dosage forms, one containing glibenclamide and the other metformin, in the same respective effective doses as in said single oral dosage form.

A pharmaceutical composition comprising a single solid oral dosage form containing an effective dose of metformin and an effective dose of glibenclamide wherein, after oral administration thereof to a human, the mean Cmax and mean AUC values of glibenclamide are, respectively, ±25% of 113 ng/ml and ±25% of 842 ng/ml/hr, for a 5 mg unit dose of glibenclamide, or proportionally higher or lower values for higher or lower unit doses of glibenclamide, respectively.

A pharmaceutical composition comprising a single solid oral dosage form containing an effective dose of metformin and an effective dose glibenclamide wherein, after oral administration thereof to a human, the adjusted geometric mean Cmax and adjusted geometric mean AUC values of glibenclamide are, respectively, ±25% of 101 ng/ml and ±25% of 780 ng/ml/hr, for a 5 mg unit dose of glibenclamide, or proportionally higher or lower values for higher or lower unit doses of glibenclamide, respectively.

A method of achieving a bioavailability of glibenclamide in a human upon administering orally a single solid oral dosage form containing an effective dose of metformin and an effective dose of glibenclamide, said bioavailability being comparable to the bioavailability of glibenclamide achieved by oral administration of separate solid oral dosage forms to a human, one containing glibenclamide and the other metformin, in the same respective effective doses as in said single oral dosage form, comprising formulating glibenclamide with metformin in said single solid oral dosage form so as to assure said comparable bioavailability.

A method of increasing bioavailability of glibenclamide in a human upon administering orally a single solid oral dosage form containing an effective dose of metformin and an effective dose of glibenclamide, such that said increased bioavailability is comparable to the bioavailability of glibenclamide achieved by oral administration of separate solid oral dosage forms to a human, one containing glibenclamide and the other metformin, in the same respective effective doses as in said single oral dosage form, comprising formulating glibenclamide with metformin in said single solid oral dosage form so as to assure said comparable bioavailability.