LEVOTHYROXINE LIQUID FORMULATIONS
The present invention is directed to a pharmaceutical product which includes a liquid formulation comprising levothyroxine or a pharmaceutically acceptable salt thereof. The formulation of the present invention includes a cyclodextrin, water, and an amine, and has a pH above the buffering range of the amine. The liquid formulation of the invention is stable and ready-to-use.
1 . A pharmaceutical product comprising an aqueous formulation for parenteral administration, the formulation comprising levothyroxine sodium at a concentration of from about 5 mcg/mL to about 100 mcg/mL and sulfobutylether β-cyclodextrin, wherein the formulation comprises an amine capable of stabilizing the levothyroxine in the formulation and has a pH above the buffering range of the amine, wherein, following storage for one week at 55° C., the formulation contains not more than 2.0% liothyronine (T3) and not more than about 5% total impurities.
2 . The pharmaceutical product of claim 1 , wherein the formulation contains not more than 2.0% liothyronine (T3).
3 . The pharmaceutical product of claim 1 , wherein the total impurities are determined after storage for two months at 40° C.
4 . The pharmaceutical product of claim 1 , wherein the formulation retains at least about 95% of the initial concentration of levothyroxine or pharmaceutically acceptable salt thereof after storage for at least 12 months at room temperature.
5 . The pharmaceutical product of claim 1 , wherein the formulation is contained within a clear glass vial.
6 . The pharmaceutical product of claim 1 , wherein the amounts of T3 and total impurities are determined by a peak area percent method using high-performance liquid chromatography (HPLC).
7 . The pharmaceutical product of claim 1 , wherein the formulation comprises levothyroxine sodium at a concentration of about 100 mcg/mL.
8 . A pharmaceutical product comprising an aqueous formulation for parenteral administration, the formulation comprising levothyroxine sodium at a concentration of about 100 mcg/mL and sulfobutylether β-cyclodextrin, wherein the formulation comprises an amine capable of stabilizing the levothyroxine in the formulation, has a pH above the buffering range of the amine, is contained within a clear glass vial, and wherein, following storage for one week at 55° C., the formulation contains not more than 2.0% liothyronine (T3) and not more than about 5% total impurities.
9 . The pharmaceutical product of claim 8 , wherein the total impurities are determined after storage for two months at 40° C.
10 . The pharmaceutical product of claim 8 , wherein the formulation retains at least about 95% of the initial concentration of levothyroxine or pharmaceutically acceptable salt thereof after storage for at least 12 months at room temperature.
11 . The pharmaceutical product of claim 8 , wherein the amounts of T3 and total impurities are determined by a peak area percent method using high-performance liquid chromatography (HPLC).