Patent EA-003960-B1 (EA)
Title: Storable biologically active substance concentrate of formoterol
Inventor: HOCHRAINER DIETER
IPC: A61M11/02
Filed: 1999-10-09
Abstract: 1. Propellant-free active substance concentrate suitable for storage containing formoterol in the form of its free base, one of the pharmacologically acceptable salts thereof or one of the addition products thereof as the active substance, in a pharmacologically acceptable solvent or suspension agent, wherein the concentration of formoterol is between 75 mg/ml and 500 mg/ml. 2. Active substance concentrate according to claim 1, characterised in that the concentration of formoterol is between 100 mg/ml and 400 mg/ml. 3. Active substance concentrate according to claim 1, characterised in that the concentration of formoterol is between 250 mg/ml and 350 mg/ml. 4. Active substance concentrate according to one of the preceding claims, characterised in that the solvent or suspension agent is a polar, preferably a protonic liquid. 5. Active substance concentrate according to one of the preceding claims, characterised in that the solvent or suspension agent is water, an aqueous saline solution, preferably a sodium chloride solution, ethanol or a mixture thereof. 6. Active substance concentrate according to one of the preceding claims 1 to 5, characterised in that the formoterol is dissolved. 7. Active substance concentrate according to one of the preceding claims 1 to 5, characterised in that the formoterol is suspended in water or an aqueous saline solution. 8. Active substance concentrate according to one of the preceding claims 1 to 7, characterised in that the formulation contains a surfactant such as sorbitan ester, preferably sorbitan trioleate, oleic acid and/or lecithin. 9. Active substance concentrate according to one of the preceding claims 1 to 8, characterised in that the active substance concentrate contains a pharmacologically acceptable acid such as e.g. hydrochloric acid, nitric acid, sulphuric acid, phosphoric acid, ascorbic acid, citric acid, malic acid, tartaric acid, malefic acid, fumaric acid, succinic acid, acetic acid, formic acid and/or propionic acid, preferably hydrochloric acid and/or fumaric acid. 10. Active substance concentrate according to one of the preceding claims 1 to 9, characterised in that the pH of the active substance concentrate is between 2.0 and 7.0, preferably between 4.0 and 6.0 and most preferably between 4.5 and 5.5. 11. Active substance concentrate according to one of the preceding claims 1 to 10, characterised in that the active substance concentrate contains a preservative, antioxidant and/or a complexing agent. 12. Active substance concentrate according to one of the preceding claims 1 to 11, characterised in that the formulation contains one or more additional inhalatively active pharmaceutical substances, preferably selected from the group comprising the betamimetics, anticholinergics, antiallergics, leukotriene antagonists and/or steroids. 13. Active substance concentrate suitable for storage, containing formoterol as active substance, characterised in that formoterol is present as a suspension in water in a concentration of between 250 mg/ml and 350 mg/ml and in that the active substance concentrate is adjusted to a pH of 4.5 to 5.5 and optionally contains a pharmacologically acceptable salt in an amount such that formoterol is dissolved to an extent of less than 0.5 % (w/w), preferably less than 0.1% (w/w). 14. Use of a formoterol active substance concentrate according to one of the preceding claims 1 to 13 for administration by inhalation, characterised in that the formulation is diluted before administration with a propellant-free, pharmacologically acceptable diluent so that the concentration of formoterol is between 0.9 and 1.5 mg/ml. 15. Use of a formoterol active substance concentrate according to claim 14, characterised in that the diluent is water, an aqueous saline solution, ethanol or a mixture thereof. 16. Use of a formoterol active substance concentrate according to claim 14, characterised in that the formoterol formulation is a formulation according to claim 13 and the diluent is a water/ethanol mixture which contains a preservative and Na-EDTA and is adjusted to a pH of between 4.5 and 5.5. 17. Formulation of a solution for inhalation therapy, containing a solvent mixture of ethanol/water which is adjusted to a pH of about 4.5 to 5.5, dissolved formoterol in a concentration of about 0.9 to 1.5 mg/ml based on formoterol, a preservative in a pharmacologically acceptable amount and Na-EDTA in a pharmacologically acceptable amount. 18. Use of a formoterol active substance concentrate according to one of claims 1 to 13 for preparing a formoterol-containing aerosol formulation for administration by inhalation. 19. Use of a formoterol active substance concentrate according to one of the preceding claims 1 to 13 and 17 in inhalators for inhalation therapy.