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 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.
2 . 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.
3 . 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.
4 . The formulation of claim 1 , wherein the formulation does not contain of any phospholipid, polysaccharide, sorbitan ester, histidine, or polyvinylpyrrolidone polymer.
5 . The formulation of claim 2 , wherein the formulation does not contain of any phospholipid, polysaccharide, sorbitan ester, histidine, or polyvinylpyrrolidone polymer.
6 . The formulation of claim 3 , wherein the formulation does not contain of any phospholipid, polysaccharide, sorbitan ester, histidine, or polyvinylpyrrolidone polymer.
7 . 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.
8 . 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.
9 . The formulation of claim 4 , 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.
10 . The formulation of claim 5 , 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.
11 . The formulation of claim 6 , 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.
12 . The formulation of claim 9 , 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.
13 . 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.
14 . The formulation of claim 11 , 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.
15 . The formulation of claim 12 , wherein the formulation comprises 1% (w/w) of the solubilizing agent and 0.05% (w/w) capsaicin.
16 . The formulation of claim 13 , wherein the formulation comprises 1% (w/w) of the solubilizing agent and 0.05% (w/w) capsaicin.
17 . The formulation of claim 14 , wherein the formulation comprises 1% (w/w) of the solubilizing agent and 0.05% (w/w) capsaicin.
18 . An aqueous, capsaicin injectable formulation, comprising:
a. 0.05% (w/w) of trans-capsaicin;
b. 1% (w/w) of a solubilizing agent, wherein the solubilizing agent is a mixture of
and polyethylene glycol; wherein the polyethylene glycolyl has a weight average molecular weight of about 660 g/mol;
c. 0.01% (w/w) dibutylhydroxytoluene;
d. 0.68% (w/w) of sodium acetate or a mixture of sodium acetate and acetic acid;
e. 0.025% (w/w) of ethylenediaminetetraacetic acid or a salt thereof;
f. 0.6% (w/w) of sodium chloride;
g. at least 97.6% (w/w) water; and
having a pH of 5.5.
19 . The formulation of claim 18 , wherein the formulation does not contain of any phospholipid, polysaccharide, sorbitan ester, histidine, or polyvinylpyrrolidone polymer.
20 . The formulation of claim 18 , wherein the formulation does not contain any cyclodextrin or hyaluronic acid.
21 . The formulation of claim 18 , 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.
22 . The formulation of claim 18 , 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.
23 . The formulation of claim 18 , 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.
24 . The formulation of claim 19 , 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.
25 . The formulation of claim 19 , 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.
26 . The formulation of claim 19 , 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.