Low-dose doxepin formulations and methods of making and using the same
The invention disclosed herein generally relates to low-dose oral doxepin pharmaceutical formulations and the use of these formulations to promote sleep.
1. A pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, and about 92% to about 99.8% w/w silicified microcrystalline cellulose.
2. The composition of claim 1 , wherein the pharmaceutical composition has dissolution and bioavailability characteristics such that after administration to a 70 kg human, the composition provides a plasma concentration of at least 0.05 ng/mL doxepin within a time frame of not more than about 90 minutes.
3. The composition of claim 1 , further comprising about 0.1 to about 1.5% w/w colloidal silicon dioxide.
4. The composition of claim 1 , further comprising about 0.25 to about 1.5% w/w magnesium stearate.
5. The composition of claim 1 , wherein the composition comprises about 0.8 to about 2 mg of doxepin or a pharmaceutically acceptable salt thereof.
6. The composition of claim 1 , wherein the composition comprises about 2.5 to about 4 mg of doxepin or a pharmaceutically acceptable salt thereof.
7. The composition of claim 1 , wherein the composition comprises about 3 mg of doxepin or a pharmaceutically acceptable salt thereof.
8. The composition of claim 1 , wherein the composition comprises about 5.5 to about 7 mg of doxepin or a pharmaceutically acceptable salt thereof.
9. The composition of claim 1 , wherein the composition comprises about 6 mg of doxepin or a pharmaceutically acceptable salt thereof.
10. The composition of claim 1 , wherein the composition comprises about 94% to about 98.5% w/w silicified microcrystalline cellulose.
11. A pharmaceutical composition comprising about 0.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, and about 92% to about 99.8% w/w silicified microcrystalline cellulose, wherein the pharmaceutical composition has dissolution and bioavailability characteristics such that after administration to a 70 kg human, the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes.
12. The composition of claim 11 , wherein the time frame to provide a plasma concentration of at least 0.1 ng/mL is not more than about 50 minutes.
13. The composition of claim 11 , further comprising about 0.1 to about 1.5% w/w colloidal silicon dioxide.
14. The composition of claim 11 , further comprising about 0.25 to about 1.5% w/w magnesium stearate.
15. The composition of claim 11 , wherein the composition comprises about 2.5 to about 4 mg of doxepin or a pharmaceutically acceptable salt thereof.
16. The composition of claim 11 , wherein the composition comprises about 3 mg of doxepin or a pharmaceutically acceptable salt thereof.
17. The composition of claim 11 , wherein the composition comprises about 5.5 to about 7 mg of doxepin or a pharmaceutically acceptable salt thereof.
18. The composition of claim 11 , wherein the composition comprises about 6 mg of doxepin or a pharmaceutically acceptable salt thereof.
19. The composition of claim 11 , wherein the composition comprises about 94% to about 98.5% w/w silicified microcrystalline cellulose.
20. A pharmaceutical composition comprising about 2.5 to about 7 mg of doxepin, or a pharmaceutically acceptable salt thereof, and about 94% to about 98.5% w/w silicified microcrystalline cellulose, wherein the pharmaceutical composition has dissolution and bioavailability characteristics such that after administration to a 70 kg human, the composition provides a plasma concentration of at least 0.1 ng/mL doxepin within a time frame of not more than about 60 minutes.