CCI-779 concentrate formulations
View Patent ↗This invention provides CCI-779 cosolvent concentrates which are useful in preparing a parenteral formulation of rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid (CCI-779) following admixture with a diluent.
1. A CCI-779 cosolvent concentrate for preparing a parenteral formulation upon admixture with a diluent, said concentrate comprising:
about 1 mg/mL to about 25 mg/mL of CCI-779;
about 15% w/v to about 60% w/v dehydrated ethanol;
about 15% w/v to about 60% w/v propylene glycol;
about 0.01% w/v to about 0.1% w/v of d,1-α-tocopherol; and
about 0.001 to about 0.005% w/v of citric acid.
2. The CCI-779 cosolvent concentrate according to claim 1 , wherein the citric acid is about 0.0025% w/v of the cosolvent concentrate.
3. The CCI-779 cosolvent concentrate according to claim 1 , wherein the dehydrated ethanol is at least about 30% w/v of the cosolvent concentrate.
4. The CCI-779 cosolvent concentrate according to claim 1 , wherein the propylene glycol is about 35% w/v to about 50% w/v of the cosolvent concentrate.
5. The CCI-779 cosolvent concentrate according to claim 1 , wherein the d,1-α-tocopherol is about 0.075% of the cosolvent concentrate.
6. The CCI-779 cosolvent concentrate according to claim 1 , comprising about 25 mg/mL CCI-779;
about 40% w/v of dehydrated ethanol;
about 0.075% w/v of d,1-α-tocopherol;
about 0.0025% w/v of citric acid; and
about 35% w/v propylene glycol.
7. The CCI-779 cosolvent concentrate according to claim 1 , which is diluted at a ratio of 1:1.5 to 1:2 concentrate to diluent to form the parenteral formulation.
8. A CCI-779 cosolvent concentrate for preparing a parenteral formulation upon admixture with a diluent, said concentrate consisting of about 1 to about 25 mg/mL of CCI-779, about 0.01 to 0.1% w/v of d,1-α-tocopherol, up to about 0.1% w/v of d,1-α-tocopherol, about 0.001 to about 0.005% w/v of citric acid, and about 15 to about 60% w/v of dehydrated ethanol and propylene glycol.
9. The CCI-779 cosolvent concentrate according to claim 8 , comprising about 40% w/v dehydrated ethanol.
10. The CCI-779 cosolvent concentrate according to claim 8 , comprising about 15% w/v to about 60% w/v propylene glycol.
11. The CCI-779 cosolvent concentrate according to claim 10 , comprising about 50% w/v propylene glycol.
12. The CCI-779 cosolvent concentrate according to claim 8 , comprising about 0.075% w/v of d,1-α-tocopherol.
13. The CCI-779 cosolvent concentrate according to claim 8 , which is diluted at a ratio of 1:1.5 to 1:2 concentrate to diluent to form the parenteral formulation.