Nasal calcitonin formulation

Abstract

A liquid pharmaceutical composition is disclosed comprising calcitonin or an acid addition salt thereof and citric acid or salt thereof in a concentration from about to about 50 mM, said composition being in a form table for nasal administration.A liquid pharmaceutical composition is provided for nasal administration of calcitonin or an acid addition salt thereof. The nasal pharmaceutical formulations contain a component selected from the group consisting of citric acid, citric acid salt and a combination thereof.

1. A liquid pharmaceutical composition comprising calcitonin or an acid addition salt thereof and citric acid and/or salt thereof in a concentration from 10 to about 50 mM, said composition being in a form suitable for nasal administration. 
     
     
       2. The liquid pharmaceutical composition of  claim 1  further comprising a pharmaceutically acceptable, aqueous liquid nasal carrier. 
     
     
       3. The liquid pharmaceutical composition of  claim 2 , wherein said carrier comprises aqueous saline. 
     
     
       4. The liquid pharmaceutical composition of  claim 1 , wherein said composition is in the form of a nasal spray. 
     
     
       5. The liquid pharmaceutical composition of  claim 4  having a viscosity of less than 0.98 cP. 
     
     
       6. The liquid pharmaceutical composition of  claim 1 , wherein the calcitonin is selected from the group consisting of salmon calcitonin, human calcitonin, porcine calcitonin and 1,7-Asu-ccl calcitonin. 
     
     
       7. The liquid pharmaceutical composition of  claim 1 , wherein the calcitonin is salmon calcitonin. 
     
     
       8. The liquid pharmaceutical composition of  claim 1 , wherein said calcitonin, or salt is present in an amount of from about 100 to about 8,000 MRC units/ml. 
     
     
       9. The liquid pharmaceutical composition of  claim 1 , wherein said calcitonin, or salt is present in an amount of from about 500 to about 4,000 MRC units/ml. 
     
     
       10. The liquid pharmaceutical composition of  claim 1 , wherein said calcitonin, or salt is present in an amount of from about 500 to about 3,000 MRC units/ml. 
     
     
       11. The liquid pharmaceutical composition of  claim 1 , wherein said calcitonin, or salt is present in an amount of from about 1,000 to about 2,500 MRC units/ml. 
     
     
       12. The liquid pharmaceutical composition of  claim 1  having a pH of from about 3 to about 5. 
     
     
       13. The liquid pharmaceutical composition of  claim 1   A liquid pharmaceutical composition for nasal administration comprising calcitonin or an acid addition salt thereof and a bioavailability enhancing agent selected from the group consisting of citric acid, citric acid salt and a combination thereof, wherein the combined concentration of all bioavailability enhancing agents is  10 - 25  mM, said composition having a pH of from about  3.5 to about  3.9. 
     
     
       14. The liquid pharmaceutical composition of claim  1    13  having a pH of about 3.7. 
     
     
       15. The liquid pharmaceutical composition of  claim 1  having an osmotic pressure of from about 250 to about 350 mOsm/liter. 
     
     
       16. The liquid pharmaceutical composition of claim  1    13  further containing at least 0.1% by weight of polyoxyethylene(20) sorbitan monooleate. 
     
     
       17. The liquid pharmaceutical composition of claim  1    13  further containing at least one preservative selected from the group consisting of benzyl alcohol, phenylethyl alcohol, methyl parabens, ethyl parabens, propyl parabens and butyl parabens. 
     
     
       18. A liquid pharmaceutical composition comprising about 2,200 MRC units of salmon calcitonin, about 10 mM citric acid, about 0.2% phenylethyl alcohol, about 0.5% benzyl alcohol, and about 0.1% polyoxyethylene(20) sorbitan monooleate. 
     
     
       19. A liquid pharmaceutical composition for nasal administration comprising about  2,200 MIC  MRC  units of salmon calcitonin, about 20 mM citric acid, about 0.2% phenylethyl alcohol, about 0.5% benzyl alcohol, and about 0.1% polyoxyethylene(20) sorbitan monooleate. 
     
     
       20. A method of administering a calcitonin to a subject requiring calcitonin treatment, which method comprises administering to said subject a composition as defined in  claim 1  via the nasal route. 
     
     
       21. The method of  claim 20 , wherein the amount of calcitonin administered is from about 200 to about 600 MRC units. 
     
     
       22. A method of improving the stability of a liquid pharmaceutical composition of calcitonin comprising adding citric acid or a salt thereof in a concentration from 10 to about 50 mM to said composition. 
     
     
       23. A method of improving the bioavailability or the concentration of plasma calcitonin in a subject following nasal administration of a liquid pharmaceutical composition of calcitonin, which method comprises adding citric acid or a salt thereof in a concentration from 10 to about 50 mM to said composition prior to said administration. 
     
     
       24. The pharmaceutical composition of  claim 13 , wherein said citric acid or citric acid salt concentration is  20  mM. 
     
     
       25. The pharmaceutical composition of  claim 13 , wherein said composition includes aqueous saline. 
     
     
       26. The pharmaceutical composition of  claim 13 , wherein said composition includes aqueous saline and has an osmotic pressure from  250  to  350  mOsm/liter. 
     
     
       27. The pharmaceutical composition of  claim 13 , wherein said composition has a viscosity of less than  0 . 98  cP. 
     
     
       28. The pharmaceutical composition of  claim 13 , wherein said calcitonin is salmon calcitonin. 
     
     
       29. The liquid pharmaceutical composition of  claim 16 , further containing at least one preservative selected from the group consisting of benzyl alcohol, phenylethyl alcohol, methyl parabens, ethyl parabens, propyl parabens and butyl parabens.