Process for the preparation of epoprostenol sodium of enhanced stability
AssigneeChinoin GyóGyszer éS VegyéSzeti TerméKek GyáRa Zrt.
InventorsIrén HORTOBÁGYI, István LÁSZLÓFI, Zsuzsanna KARDOS, József MOLNÁR, László TAKÁCS, Róbertné TORMÁSI
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Abstract
The invention provides a stable epoprostenol sodium and a process for the preparation this pharmaceutically active ingredient.
Claims15
Stable epoprostenol sodium drug substance which can be stored in deep freezer (−20±5° C.) for at least 3 years, characterized by that the lyophilized drug substance contains epoprostenol sodium salt and, related to the amount of the epoprostenol sodium salt, it contains in 3-7.5 mass % inorganic base or basic-hydrolyzing inorganic salt.
Process for the preparation of stable epoprostenol sodium which can be stored in deep freezer (−20±5° C.) for at least 3 years, characterized by that the aqueous solution of the epoprostenol sodium salt is lyophilized in the presence of such an amount of inorganic base or basic-hydrolyzing inorganic salt ensuring a pH>11 medium, that the lyophilisate contains 3-7.5 mass %, preferably 4-6 mass % of excess sodium hydroxide, related to the amount of the epoprostenol sodium salt.
Process for the preparation of stable epoprostenol sodium comprising cyclisation with iodine and by hydrogen iodide elimination, wherein
- a.) as starting material unprotected PGF2α is applied,
- b.) as iodine source, sodium iodide-sodium iodate mixture is applied,
- c.) the cyclisation and the hydrogen iodide elimination are performed in the same solvent,
- d.) the aqueous solution of the epoprostenol sodium salt is lyophilized in the presence of inorganic base or basic-hydrolysing inorganic salt ensuring a pH>11 medium.
Dependencies are inferred from the claim text.