Stabilized efinaconazole compositions as antifungals
The present invention provides compositions containing efinaconazole, butylated hydroxytoluene, a salt of ethylenediaminetetraacetic acid, and optional citric acid. The compositions exhibit stable color profiles and are useful in the treatment of fungal infections.
1. A semisolid composition comprising:
(a) about 0.5% to about 15% efinaconazole (w/w);
(b) butylated hydroxytoluene (BHT); and
(c) a salt of ethylenediaminetetraacetic acid (EDTA);
wherein the amounts of butylated hydroxytoluene (BHT) and salt of ethylenediaminetetraacetic acid (EDTA) are sufficient to ensure that the semisolid composition is:
(i) colorless upon initial formulation; and
(ii) colorless or pale yellow after storage for at least three weeks at a temperature of at least 40° C.
2. The semisolid composition of claim 1 , wherein the amount of efinaconazole in the semisolid composition is in the range of about 0.5% (w/w) to about 5% (w/w).
3. The semisolid composition of claim 2 , wherein the amount of efinaconazole in the semisolid composition is about 2% (w/w).
4. The semisolid composition of claim 1 , wherein the amount of butylated hydroxytoluene (BHT) in the semisolid composition is in the range of about 0.01% (w/w) to about 2% (w/w).
5. The semisolid composition of claim 1 , wherein the amount of the salt of ethylenediaminetetraacetic acid (EDTA) in the semisolid composition is in the range of about 0.0001% (w/w) to about 1.5% (w/w).
6. The semisolid composition of claim 5 , wherein the amount of the salt of ethylenediaminetetraacetic acid (EDTA) in the semisolid composition is in the range of about 0.01% (w/w) to about 1% (w/w).
7. The semisolid composition of claim 1 , wherein the semisolid composition further comprises citric acid in an amount in the range of about 0.01% (w/w) to about 1% (w/w).
8. The semisolid composition of claim 7 , wherein the semisolid composition further comprises citric acid in an amount in the range of about 0.05% (w/w) to about 0.25% (w/w).
9. The semisolid composition of claim 8 , wherein the semisolid composition further comprises citric acid in an amount in the range of about 0.075% (w/w) to about 0.15% (w/w).
10. The semisolid composition of claim 1 , wherein the semisolid composition is colorless or pale yellow after storage for one month at a temperature of about 65° C.
11. The semisolid composition of claim 1 , wherein the color of the semisolid composition is determined by visual inspection.
12. The semisolid composition of claim 1 , wherein the color of the semisolid composition is determined by assessing ultraviolet-visible (UV-vis) absorbance values.
13. The semisolid composition of claim 12 , wherein after storage for at least one month at a temperature of 65° C., the semisolid composition exhibits ultraviolet-visible (UV-vis) absorbance values according to any one of (i), (ii), (iii), (iv), (v), (vi), or (vii):
(i) 0.1 absorbance units (AU) or less at 400 nm; or
(ii) 0.01 absorbance units (AU) or less at 500 nm; or
(iii) 0.01 absorbance units (AU) or less at 600 nm; or
(iv) 0.1 absorbance units (AU) or less at 400 nm; and
0.01 absorbance units (AU) or less at 500 nm; or
(v) 0.1 absorbance units (AU) or less at 400 nm; and
0.01 absorbance units (AU) or less at 600 nm; or
(vi) 0.01 absorbance units (AU) or less at 500 nm; and
0.01 absorbance units (AU) or less at 600 nm; or
(vii) 0.1 absorbance units (AU) or less at 400 nm;
0.01 absorbance units (AU) or less at 500 nm; and
0.01 absorbance units (AU) or less at 600 nm.
14. The semisolid composition of claim 12 , wherein after storage for at least one month at a temperature of 65° C., the semisolid composition exhibits ultraviolet-visible (UV-vis) absorbance values according to any one of (i), (ii), (iii), (iv), (v), (vi), or (vii):
(i) 0.2 absorbance units (AU) or less at 400 nm; or
(ii) 0.03 absorbance units (AU) or less at 500 nm; or
(iii) 0.03 absorbance units (AU) or less at 600 nm; or
(iv) 0.2 absorbance units (AU) or less at 400 nm; and
0.03 absorbance units (AU) or less at 500 nm; or
(v) 0.2 absorbance units (AU) or less at 400 nm; and
0.03 absorbance units (AU) or less at 600 nm; or
(vi) 0.03 absorbance units (AU) or less at 500 nm; and
0.03 absorbance units (AU) or less at 600 nm; or
(vii) 0.2 absorbance units (AU) or less at 400 nm;
0.03 absorbance units (AU) or less at 500 nm; and
0.03 absorbance units (AU) or less at 600 nm.
15. The semisolid composition of claim 12 , wherein after storage for at least one month at a temperature of 65° C., the semisolid composition exhibits ultraviolet-visible (UV-vis) absorbance values according to any one of (i), (ii), (iii), (iv), (v), (vi), or (vii):
(i) 0.4 absorbance units (AU) or less at 400 nm; or
(ii) 0.1 absorbance units (AU) or less at 500 nm; or
(iii) 0.1 absorbance units (AU) or less at 600 nm; or
(iv) 0.4 absorbance units (AU) or less at 400 nm; and
0.1 absorbance units (AU) or less at 500 nm; or
(v) 0.4 absorbance units (AU) or less at 400 nm; and
0.1 absorbance units (AU) or less at 600 nm; or
(vi) 0.1 absorbance units (AU) or less at 500 nm; and
0.1 absorbance units (AU) or less at 600 nm; or
(vii) 0.4 absorbance units (AU) or less at 400 nm;
0.1 absorbance units (AU) or less at 500 nm; and
0.1 absorbance units (AU) or less at 600 nm.
16. The semisolid composition of claim 1 , wherein the semisolid composition is formulated as a gel, an ointment, a lotion, or a cream.
17. The semisolid composition of claim 6 , wherein the semisolid composition is formulated as a gel.
18. The semisolid composition of claim 17 , wherein the amount of the salt of ethylenediaminetetraacetic acid (EDTA) in the semisolid composition is about 0.1% (w/w) and the amount of butylated hydroxytoluene (BHT) is about 0.1% (w/w).
19. A pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier, diluent, or excipient and the semisolid composition of claim 1 .
20. A method for treating a fungal infection in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of the pharmaceutical formulation of claim 19 .
21. The method of claim 20 , wherein the method further comprises administering a therapeutically effective amount of the pharmaceutical formulation to one or more nails of the patient.