Reconstitutable teverelix-TFA composition
The present invention relates to a reconstitutable teverelix-TFA composition having a predefined molar ratio of teverelix to trifluoroacetate which is below the molar ratio required for microcrystal formation. Said composition remains stable during storage e.g., at a temperature around 2-8° C. Upon reconstitution a fixed amount of trifluoroacetate can be added to said composition thereby effectively and simply achieving an exact and desired molar ratio in order to obtain a fluid, milky microcrystalline aqueous teverelix-TFA suspension.
1 . A method of preparing a reconstitutable teverelix-trifluoroacetate (TFA) composition, wherein said method comprises
mixing teverelix and trifluoroacetate at a molar ratio of between 1:1.3 and 1:1.6, as determined by measuring a content of trifluoroacetate and teverelix in an aqueous teverelix-TFA solution using an HPLC method, thereby providing the aqueous teverelix-TFA solution without any microcrystals, and
drying the aqueous teverelix-TFA solution.
2 . The method according to claim 1 , wherein the aqueous teverelix-TFA solution is dried to an extent such that the provided reconstitutable teverelix-TFA composition comprises water in an amount of between 0.3% to 5% by weight based on the total weight of the reconstitutable teverelix-TFA composition.
3 . The method according to claim 1 , wherein said method comprises adjusting the molar ratio in the aqueous teverelix-TFA solution to a specific predefined molar ratio between 1:1.3 and 1:1.6 by adding trifluoroacetate to the aqueous teverelix-TFA solution before said aqueous teverelix-TFA solution is dried.
4 . The method according to claim 1 , wherein said method comprises drying the aqueous teverelix-TFA solution to a water content between 0.3% to 5% by weight based on the total weight of the reconstitutable teverelix-TFA composition.
5 . A reconstitutable teverelix-trifluoroacetate (TFA) composition having a molar ratio of teverelix (Ac-D-Nal-D-pClPhe-D-Pal-Ser-Tyr-D-Hci-Leu-Lys (iPr)-Pro-D-Ala-NH 2 ) to trifluoroacetate between 1:1.3 and 1:1.6, as determined by measuring a content of trifluoroacetate and teverelix in an aqueous teverelix-TFA solution using an HPLC method, and wherein said composition does not comprise any microcrystals.
6 . The reconstitutable composition according to claim 5 , wherein water is present in the reconstitutable teverelix-TFA composition in an amount between 0.3% to 5% by weight based on the total weight of the reconstitutable teverelix-TFA composition.
7 . The reconstitutable composition according to claim 5 , wherein water is present in the reconstitutable teverelix-TFA composition in an amount between 1% by weight and 2% by weight.
8 . The reconstitutable composition according to claim 5 , wherein the reconstitutable composition is a powder or a cake.
9 . The reconstitutable composition according to claim 5 , wherein the reconstitutable composition is a powder obtained by lyophilization or spray-drying or a cake obtained by lyophilization.
10 . A package comprising a unit dosage of a reconstitutable teverelix-TFA composition having a molar ratio of teverelix (Ac-D-Nal-D-pClPhe-D-Pal-Ser-Tyr-D-Hci-Leu-Lys (iPr)-Pro-D-Ala-NH 2 ) to trifluoroacetate between 1:1.3 and 1:1.6, as determined by measuring a content of trifluoroacetate and teverelix in an aqueous teverelix-TFA solution using an HPLC method, and wherein said composition does not comprise any microcrystals.