Stable aqueous capsaicin injectable formulations and medical uses thereof
The invention provides stable, aqueous capsaicin injectable formulations, a unit dose containing such injectable formulations, medical kits, and methods for using such injectable formulations and unit doses to treat patients suffering from pain, such as osteoarthritic knee pain. The stable, aqueous capsaicin injectable formulations may contain, for example, capsaicin, a solubilizing agent (e.g., a polyethylene glycol ester of a (C 15 -C 25 ) hydroxyalkanoic acid), an antioxidant, and water.
1. An aqueous, capsaicin injectable formulation, comprising
a. about 0.04% (w/w) to about 0.06% (w/w) of capsaicin;
b. about 0.5% (w/w) to about 1.5% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises
and polyethylene glycol;
c. about 0.005% (w/w) to about 0.015% (w/w) of an antioxidant;
d. about 0.2% (w/w) to about 1% (w/w) of an alkali metal acetate;
e. about 0.01% (w/w) to about 0.05% (w/w) of a chelating agent;
f. about 0.3% (w/w) to about 0.9% (w/w) of a tonicity modifier;
g. at least 96% (w/w) water; and
having a pH in the range of about 5 to about 6.
2. The formulation of claim 1 , wherein the solubilizing agent comprises (a) from 68% (w/w) to 72% (w/w) of a mixture of
and (b) from 28% (w/w) to 32% (w/w) polyethylene glycol.
3. The formulation of claim 1 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 300 g/mol to about 900 g/mol.
4. The formulation of claim 2 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 300 g/mol to about 900 g/mol.
5. The formulation of claim 2 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol.
6. The formulation of claim 2 , wherein any polyethylene glycolyl has a weight-average molecular weight of about 660 g/mol.
7. The formulation of claim 5 , wherein the formulation has an osmolality in the range of from about 240 mOsm/kg to about 340 mOsm/kg.
8. The formulation of claim 1 , wherein less than 0.5% of the capsaicin degrades upon storage at 40° C. for 24 weeks.
9. The formulation of claim 7 , wherein less than 0.5% of the capsaicin degrades upon storage at 40° C. for 24 weeks.
10. An aqueous, capsaicin injectable formulation, comprising
a. about 0.04% (w/w) to about 0.06% (w/w) of capsaicin;
b. about 0.8% (w/w) to about 1.2% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises
and polyethylene glycol;
c. about 0.005% (w/w) to about 0.015% (w/w) of dibutylhydroxytoluene;
d. about 0.2% (w/w) to about 1% (w/w) of sodium acetate;
e. about 0.01% (w/w) to about 0.05% (w/w) of ethylenediaminetetraacetic acid or a salt thereof;
f. about 0.3% (w/w) to about 0.9% (w/w) of sodium chloride;
g. at least 96% (w/w) water; and
having a pH in the range of about 5 to about 6.
11. The formulation of claim 10 , wherein the solubilizing agent comprises (a) from 68% (w/w) to 72% (w/w) of a mixture of
and (b) from 28% (w/w) to 32% (w/w) polyethylene glycol.
12. The formulation of claim 10 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 300 g/mol to about 900 g/mol.
13. The formulation of claim 11 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 300 g/mol to about 900 g/mol.
14. The formulation of claim 11 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol.
15. The formulation of claim 11 , wherein any polyethylene glycolyl has a weight-average molecular weight of about 660 g/mol.
16. The formulation of claim 14 , wherein the formulation has an osmolality in the range of from about 240 mOsm/kg to about 340 mOsm/kg.
17. The formulation of claim 10 , wherein less than 0.5% of the capsaicin degrades upon storage at 40° C. for 24 weeks.
18. The formulation of claim 16 , wherein less than 0.5% of the capsaicin degrades upon storage at 40° C. for 24 weeks.
19. The formulation of claim 10 , wherein the formulation comprises
a. about 0.04% (w/w) to about 0.06% (w/w) of capsaicin;
b. about 0.8% (w/w) to about 1.2% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises (a) about 70% (w/w) of a mixture of
and (b) about 30% (w/w) polyethylene glycol;
c. about 0.005% (w/w) to about 0.015% (w/w) of dibutylhydroxytoluene;
d. about 0.2% (w/w) to about 1% (w/w) of sodium acetate;
e. about 0.01% (w/w) to about 0.05% (w/w) of ethylenediaminetetraacetic acid or a salt thereof;
f. about 0.3% (w/w) to about 0.9% (w/w) of sodium chloride;
g. at least 96% (w/w) water; and
having a pH in the range of about 5 to about 6.
20. The formulation of claim 19 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol.
21. The formulation of claim 19 , wherein any polyethylene glycolyl has a weight-average molecular weight of about 660 g/mol.
22. The formulation of claim 21 , wherein less than 0.5% of the capsaicin degrades upon storage at 40° C. for 24 weeks.
23. An aqueous, capsaicin injectable formulation, comprising
a. about 0.05% (w/w) of capsaicin;
b. about 1% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises
and polyethylene glycol;
c. about 0.005% (w/w) to about 0.015% (w/w) of dibutylhydroxytoluene;
d. about 0.2% (w/w) to about 1% (w/w) of sodium acetate;
e. about 0.01% (w/w) to about 0.05% (w/w) of ethylenediaminetetraacetic acid or a salt thereof;
f. about 0.3% (w/w) to about 0.9%, (w/w) of sodium chloride;
g. at least 96% (w/w) water; and
having a pH of about 5.5.
24. The formulation of claim 23 , wherein the solubilizing agent comprises (a) from 68% (w/w) to 72% (w/w) of a mixture of
and (b) from 28% (w/w) to 32% (w/w) polyethylene glycol.
25. The formulation of claim 23 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 500 g/mol to about 800 g/mol.
26. The formulation of claim 24 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 500) g/mol to about 800 g/mol.
27. The formulation of claim 24 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol.
28. The formulation of claim 24 , wherein any polyethylene glycolyl has a weight-average molecular weight of about 660 g/mol.
29. The formulation of claim 27 , wherein the formulation has an osmolality in the range of from about 240 mOsm/kg to about 340 mOsm/kg.
30. The formulation of claim 27 , wherein less than 0.5% of the capsaicin degrades upon storage at 40° C. for 24 weeks.