Pharmaceutical compositions of tedizolid phosphate
Disclosed are pharmaceutical compositions comprising tedizolid phosphate, methods of preparing such pharmaceutical compositions, and methods of treating bacterial infections with such pharmaceutical compositions. Specifically, a pharmaceutical composition comprising tedizolid phosphate, an acid; and a suspending agent; and wherein the pH of the composition upon constitution with water is between about pH 2-4.5, is provided, wherein the acid is not citric acid or malic acid.
1. A pharmaceutical composition comprising:
(a) about 1-28% by weight of tedizolid phosphate, or a pharmaceutically acceptable salt thereof; and
(b) about 0.2-14% by weight of a suspending agent; and
wherein the pH of the composition upon constitution with water is between about pH 3-5.5.
2. The pharmaceutical composition of claim 1 further comprising about 0.2-14% by weight of an acid.
3. The pharmaceutical composition of claim 2 additionally comprising
a) about 45-98.5% by weight of a filler; and/or
b) about 0.1-7% by weight of a glidant.
4. The pharmaceutical composition of claim 2 additionally comprising about 0.1-4% by weight of an antimicrobial agent.
5. The pharmaceutical composition of claim 3 wherein
the filler is selected from:
1) sugar,
2) mannitol, and
3) microcrystalline cellulose; and
the glidant is selected from:
1) colloidal silicon dioxide,
2) calcium phosphate tribasic,
3) magnesium silicate, and
4) talc.
6. The pharmaceutical composition of claim 2 wherein
(a) about 1.5-10% by weight of tedizolid phosphate, or a pharmaceutically acceptable salt thereof;
(b) about 0.8-4% by weight of an acid; and
(c) about 0.5-3% by weight of a suspending agent; and
wherein the pH of the composition upon constitution with water is between about pH 3-5.5, provided that the acid is not citric acid or malic acid.
7. The pharmaceutical composition of claim 6 wherein
the acid is selected from:
1) succinic acid, and
2) fumaric acid; and
the suspending agent is selected from:
1) xanthan gum,
2) guar gum,
3) sodium carboxymethylcellulose, and
4) a mixture of sodium carboxymethylcellulose and microcrystalline cellulose.
8. The pharmaceutical composition of claim 4 wherein
the antimicrobial agent is selected from:
1) methylparabens,
2) potassium sorbate,
3) propylparabens, and
4) sodium benzoate.
9. The pharmaceutical composition of claim 5 wherein the acid is succinic acid; the suspending agent is xanthan gum; the filler is sugar; and the glidant is colloidal silicon dioxide.
10. The pharmaceutical composition of claim 8 wherein the antimicrobial agent is potassium sorbate.
11. A pharmaceutical composition comprising:
a) about 1-28% by weight of tedizolid phosphate;
b) about 0.2-14% by weight of an acid;
c) about 0.2-14% by weight of a suspending agent;
d) about 45-98.5% by weight of a filler;
e) about 0.1-7% by weight of a glidant; and
f) optionally about 0.1-4% by weight of an antimicrobial agent; and
wherein the pH of the composition upon constitution with water is between about pH 3-5.5, provided that the acid is not citric acid or malic acid.
12. A pharmaceutical composition comprising:
a) about 1.5-10% by weight of tedizolid phosphate;
b) about 0.8-4% by weight of an acid;
c) about 0.5-3% by weight of a suspending agent;
d) about 80-96% by weight of a filler;
e) about 0.3-1.5% by weight of a glidant; and
f) optionally about 0.2-1% by weight of an antimicrobial agent; and
wherein the pH of the composition upon constitution with water is between about pH 3-5.5, provided that the acid is not citric acid or malic acid.
13. The pharmaceutical composition of claim 3 comprising:
a) about 7.2% by weight of tedizolid phosphate;
b) about 1.7% by weight of an acid;
c) about 1.1% by weight of a suspending agent;
d) about 89.1% by weight of a filler;
e) about 0.5% by weight of a glidant; and
f) optionally about 0.4% by weight of an antimicrobial agent; and
wherein the pH of the composition upon constitution with water is between about pH 3-5.5, provided that the acid is not citric acid or malic acid; wherein the pharmaceutical composition is constituted with water to give a 20 mg/mL dosage strength.
14. The pharmaceutical composition of claim 3 comprising:
a) about 1.9% by weight of tedizolid phosphate;
b) about 1.8% by weight of an acid;
c) about 1.1% by weight of a suspending agent;
d) about 94.1% by weight of a filler;
e) about 0.6% by weight of a glidant; and
f) optionally about 0.4% by weight of an antimicrobial agent; and
wherein the pH of the composition upon constitution with water is between about pH 3-5.5, provided that the acid is not citric acid or malic acid; and wherein, the pharmaceutical composition is constituted with water to give a 5 mg/mL dosage strength.
15. The pharmaceutical composition of claim 3 comprising:
a) about 7.2% by weight of tedizolid phosphate;
b) about 2.2% by weight of an acid;
c) about 1.1% by weight of a suspending agent;
d) about 88.4% by weight of a filler;
e) about 0.5% by weight of a glidant; and
f) optionally about 0.6% by weight of an antimicrobial agent; and
wherein the pH of the composition upon constitution with water is between about pH 3-5.5, provided that the acid is not citric acid or malic acid; and wherein the pharmaceutical composition is constituted with water to give a 20 mg/mL dosage strength.
16. The pharmaceutical composition of claim 3 wherein
the acid is selected from:
1) succinic acid, and
2) fumaric acid;
the suspending agent is selected from:
1) xanthan gum,
2) guar gum,
3) sodium carboxymethylcellulose, and
4) a mixture of sodium carboxymethylcellulose and microcrystalline cellulose;
the filler is selected from:
1) sugar,
2) mannitol, and
3) microcrystalline cellulose; and
the glidant is selected from:
1) colloidal silicon dioxide,
2) calcium phosphate tribasic,
3) magnesium silicate, and
4) talc.
17. The pharmaceutical composition of claim 16 wherein the acid is succinic acid; the suspending agent is xanthan gum; the filler is sugar; the glidant is colloidal silicon dioxide.
18. The pharmaceutical composition of claim 16 wherein the antimicrobial agent is potassium sorbate.
19. The pharmaceutical composition of claim 3 comprising:
a) about 7.21% by weight of tedizolid phosphate;
b) about 1.08% by weight of xanthan gum;
c) about 89.06% by weight of sugar; and
d) about 1.75% by weight of succinic acid.
20. The pharmaceutical composition of claim 1 wherein tedizolid phosphate is present in an unit dosage strength of 20 mg/mL or 5 mg/mL after constitution with water.
21. The pharmaceutical composition of claim 1 wherein the composition is a powder for oral suspension dosage form.
22. A method of treating a bacterial infection in a human in need thereof comprising orally administering to the human a pharmaceutical composition of claim 1 .
23. The method of claim 22 wherein the bacterial infection is a gram positive bacterial infection.
24. The method of claim 22 wherein the bacterial infection is selected from: a Staphylococcus aureus infection, a methicillin-resistant Staphylococcus aureus infection, a methicillin-susceptible Staphylococcus aureus infection, a Streptococcus pyogenes infection, a Streptococcus agalactiae infection, a Streptococcus anginosus infection, a Streptococcus intermedius infection, a Streptococcus constellatus infection, and an Enterococcus faecalis infection.