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. 0.04% (w/w) to 0.06% (w/w) of capsaicin;
b. 0.5% (w/w) to 1.5% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises
and polyethylene glycol;
c. 0.005% (w/w) to 0.015% (w/w) of an antioxidant;
d. 0.2% (w/w) to 1% (w/w) of an alkali metal acetate;
e. 0.01% (w/w) to 0.05% (w/w) of a chelating agent;
f. 0.3% (w/w) to 0.9% (w/w) of a tonicity modifier;
g. at least 96% (w/w) water; and
having a pH of 5.5;
wherein the formulation does not contain of any phospholipid, polysaccharide, protein polymer, cellulose, sorbitan ester, histidine, or polyvinylpyrrolidone polymer.
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 300 g/mol to 900 g/mol.
4. The formulation of claim 1 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of 600 g/mol to 750 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 600 g/mol to 750 g/mol.
6. The formulation of claim 1 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight of about 660 g/mol.
7. The formulation of claim 2 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight of about 660 g/mol.
8. The formulation of claim 1 , wherein the formulation has an osmolality in the range of from about 240 mOsm/kg to about 340 mOsm/kg.
9. 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.
10. The formulation of claim 1 , wherein less than 0.5% of the capsaicin degrades upon storage of the formulation at 25° C. for 24 weeks.
11. The formulation of claim 2 , wherein less than 0.5% of the capsaicin degrades upon storage of the formulation at 25° C. for 24 weeks.
12. The formulation of claim 5 , wherein less than 0.5% of the capsaicin degrades upon storage of the formulation at 25° C. for 24 weeks.
13. The formulation of claim 9 , wherein less than 0.5% of the capsaicin degrades upon storage of the formulation at 25° C. for 24 weeks.
14. The formulation of claim 1 , wherein a 2 mL aliquot of the formulation that has been stored at 25° C. and 60% Relative Humidity for a duration of 3 months contains less than 6000 particles having an average diameter of ≥10 μm.
15. The formulation of claim 1 , wherein a 2 mL aliquot of the formulation that has been stored at 25° C. and 60% Relative Humidity for a duration of 3 months contains less than 3000 particles having an average diameter of ≥10 μm.
16. The formulation of claim 1 , wherein a 2 mL aliquot of the formulation that has been stored at 25° C. and 60% Relative Humidity for a duration of 3 months contains less than 1000 particles having an average diameter of ≥10 μm.
17. The formulation of claim 5 , wherein a 2 mL aliquot of the formulation that has been stored at 25° C. and 60% Relative Humidity for a duration of 3 months contains less than 1000 particles having an average diameter of ≥10 μm.
18. The formulation of claim 1 , wherein a 2 mL aliquot of the formulation that has been stored at 25° C. and 60% Relative Humidity for a duration of 3 months contains less than 500 particles having an average diameter of ≥10 μm.
19. The formulation of claim 5 , wherein a 2 mL aliquot of the formulation that has been stored at 25° C. and 60% Relative Humidity for a duration of 3 months contains less than 500 particles having an average diameter of ≥10 μm.
20. The formulation of claim 13 , wherein a 2 mL aliquot of the formulation that has been stored at 25° C. and 60% Relative Humidity for a duration of 3 months contains less than 500 particles having an average diameter of ≥10 μm.