High-Stability Packaged Solutions of T4 Thyroid Hormone

Abstract

The invention relates to highly stable alcohol-free, water-glycerol solutions of T4 thyroid hormone, with a reduced amount of T3 impurity, packaged via specific container arrangements. The containers are multi-barrier ones, in which a number of layers of specific materials separate the solution from contact with the external environment.

1 . A pharmaceutical preparation of T4 thyroid hormone, in ready-to-use packaging, consisting of a container pre-filled with an alcohol-free water-glycerol solution of hormone T4, said container being selected from:
 (a) a one-component LDPE plastic container, placed in a sealed sachet consisting of laminated films made of a plurality of different materials selected from the following: polyethylene, aluminium, polyethylene terephthalate, ionomer resins, paper, ethylene vinyl alcohol, copolymer resins, propylene, and fluorinated-chlorinated resins; or   (b) a multi-component laminated plastic container, said container comprising multiple layers of plastic materials selected from: polyethylene, ethylene vinyl alcohol copolymer resins, polyvinyl chloride, polyvinylidene chloride; polyvinyl acetate, fluorinated-chlorinated resins, ionomer resins, cyclic olefin copolymers, polyamide, polystyrene, polycarbonate, laminated metals and aluminium bonded to plastics.   
     
     
         2 . A pharmaceutical preparation according to  claim 1 , wherein the T4/glycerol weight ratio in the water-glycerol solution is in the range from about 4 to about 400 ppm. 
     
     
         3 . A pharmaceutical preparation according to  claim 1 , wherein the water-glycerol solution contains less than about 2.5% of T3 impurity. 
     
     
         4 . A pharmaceutical preparation according to  claim 1 , wherein the water-glycerol solution contains less than about 2.0% of T3 impurity. 
     
     
         5 . A pharmaceutical preparation according to  claim 1 , wherein the water-glycerol solution contains less than about 1.8% of T3 impurity. 
     
     
         6 . A pharmaceutical preparation according to  claim 1 , wherein the preparation is in a single-dose form and contains about 5 μg to about 350 m T4 thyroid hormone. 
     
     
         7 . A pharmaceutical preparation according to  claim 1 , wherein the preparation is in a single-dose form and contains about 5 μg to about 250 m T4 thyroid hormone. 
     
     
         8 . A pharmaceutical preparation according to  claim 1 , wherein the plastic container has a thickness of between about 150 μm to about 1000 μm. 
     
     
         9 . A pharmaceutical preparation according to  claim 1 , wherein the plastic container has a thickness of between about 200 μm and about 800 μm. 
     
     
         10 . A pharmaceutical preparation according to  claim 1 , wherein the sachet comprises laminated films selected from the group consisting of: polyethylene, aluminium and polyethylene terephthalate; polyethylene, aluminium and paper; or the group consisting of ionomer resins, aluminium and paper. 
     
     
         11 . A pharmaceutical preparation according to  claim 1 , wherein the sachet has an overall thickness of between about 40 and about 100 μm. 
     
     
         12 . A pharmaceutical preparation according to  claim 1 , wherein the sachet has an overall thickness of between about 50 and about 90 μm. 
     
     
         13 . A method of treating a disease associated with T3 and/or T4 hormone deficiency, the method comprising administering a pharmaceutical preparation according to  claim 1  to a patient in need thereof. 
     
     
         14 . A pharmaceutical preparation comprising:
 (a) a composition of an alcohol-free water/glycerol solution of T4 thyroid hormone;   (b) a single-dose container for containing the solution;   whereby less than 2.5% of the T4 thyroid hormone in the solution converts to T3 thyroid hormone after 12 months under Long Term Storage Conditions.   
     
     
         15 . A pharmaceutical preparation according to  claim 14  wherein the conversion of T4 thyroid hormone to T3 thyroid hormone is less than for a pharmaceutical preparation in a similar single-dose container comprising a water-glycerol-alcohol solution of T4 thyroid hormone after 12 months under Long-Term Storage Conditions. 
     
     
         16 . A pharmaceutical composition comprising an alcohol-free water/glycerol solution of T4 thyroid hormone that is capable of storage in a single-dose container whereby the pharmaceutical composition demonstrates less the 2.5% conversion of T4 thyroid hormone to T3 thyroid hormone for 12 months under Long Term Storage Conditions. 
     
     
         17 . A method of treating thyroid hormone deficiency comprising administering the composition of the alcohol-free water/glycerol solution of T4 thyroid hormone according to  claim 14  to a patient in need thereof. 
     
     
         18 . A method of treating thyroid hormone deficiency comprising administering a pharmaceutical composition according to  claim 16  to a patient in need thereof. 
     
     
         19 . A ready-to-use pharmaceutical preparation of T4 thyroid hormone packaged in a container which is pre-filled with an alcohol-free water-glycerol solution of hormone T4, said container being selected from:
 (a) a one-component LDPE plastic container, placed in a sealed sachet consisting of laminated films made of a plurality of materials selected from the following: polyethylene, aluminium, polyethylene terephthalate, ionomer resins, paper, ethylene vinyl alcohol, copolymer resins, propylene, and fluorinated-chlorinated resins; or   (b) a multi-component laminated plastic container comprising a plurality of layers of plastic materials selected from the group consisting of: polyethylene, ethylene vinyl alcohol copolymer resins, polyvinyl chloride, polyvinylidene chloride, polyvinyl acetate, fluorinated-chlorinated resins, ionomer resins, cyclic olefin copolymers, polyamide, polystyrene, polycarbonate, laminated metals, aluminium bonded to plastics, and combinations thereof.   
     
     
         20 . A ready-to-use package of a pharmaceutical preparation of T4 thyroid hormone, the package comprising a container which is pre-filled with an alcohol-free water-glycerol solution of hormone T4, wherein the container is selected from:
 (a) a one-component LDPE plastic container, placed in a sealed sachet formed from laminated films comprising a plurality of materials selected from the following: polyethylene, aluminium, polyethylene terephthalate, ionomer resins, paper, ethylene vinyl alcohol, copolymer resins, propylene, and fluorinated-chlorinated resins; or   (b) a multi-component laminated plastic container comprising a plurality of layers of plastic materials selected from the group consisting of: polyethylene, ethylene vinyl alcohol copolymer resins, polyvinyl chloride, polyvinylidene chloride, polyvinyl acetate, fluorinated-chlorinated resins, ionomer resins, cyclic olefin copolymers, polyamide, polystyrene, polycarbonate, laminated metals, aluminium bonded to plastics, and combinations thereof.   
     
     
         21 . A method of treating patients who undergo bariatric surgery, patients whose gastric pH is altered and have absorption problems, or patients having absorption problems caused by intake of food, the method comprising administering the composition of the pharmaceutical preparation according to  claim 14  to a patient in need thereof.