Nasal calcitonin formulation
View Patent ↗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.