Synthetic progestogens and pharmaceutical compositions comprising the same
Described herein are synthetic progestogens, such as 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone, as well as pharmaceutical compositions comprising the same. Also described are methods of use.
1. A pharmaceutical composition comprising:
6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone in the form of particles that have: (i) a median particle size ranging from 10 micrometers (μm) to 30 μm; (ii) a d90 particle size of less than 100 μm; and (iii) a d10 particle size of more than 3 μm, wherein the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone is present in an amount ranging from 3 milligrams (mg) to 4.5 mg; and
one or more pharmaceutically acceptable excipients,
wherein the pharmaceutical composition does not comprise estrogen; and
wherein the pharmaceutical composition is formulated such that no more than 50% of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone initially present in the pharmaceutical composition is dissolved within 30 minutes if subjected to an in vitro dissolution test according to the USP XXIII Paddle Method.
2. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises a filler.
3. The pharmaceutical composition of claim 2 , wherein the filler comprises lactose anhydrous, microcrystalline cellulose, starch, pregelatinized starch, modified starch, dibasic calcium phosphate dihydrate, calcium sulfate trihydrate, calcium sulfate dihydrate, calcium carbonate, lactose, dextrose, sucrose, mannitol and sorbitol, or a combination thereof.
4. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises a lubricant.
5. The pharmaceutical composition of claim 4 , wherein the lubricant comprises magnesium stearate, calcium stearate, zinc stearate, talc, propylene glycol, PEG, stearic acid, vegetable oil, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, mineral oil polyoxyethylene monostearate, or a combination thereof.
6. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises a binder.
7. The pharmaceutical composition of claim 6 , wherein the binder comprises a starch, a gum, microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, or a combination thereof.
8. The pharmaceutical composition of claim 7 , wherein the starch comprises potato starch, wheat starch, corn starch, or a combination thereof.
9. The pharmaceutical composition of claim 7 , wherein the gum comprises gum tragacanth, acacia gum, gelatin, or a combination thereof.
10. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises a glidant.
11. The pharmaceutical composition of claim 10 , wherein the glidant comprises silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc, tribasic calcium phosphate, or a combination thereof.
12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises one or more additional excipients.
13. The pharmaceutical composition of claim 12 , wherein the one or more additional excipients are present in an amount ranging from 0.1% to 10%, by weight, of the pharmaceutical composition.
14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated as a tablet or a capsule.
15. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition further comprises a coating.
16. The pharmaceutical composition of claim 15 , wherein the coating comprises hydroxypropylmethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, or a combination thereof.
17. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated such that at least 55% of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone initially present in the pharmaceutical composition is dissolved within 4 hours if subjected to the in vitro dissolution test according to the USP XXIII Paddle Method.
18. The pharmaceutical composition of claim 1 , wherein the amount of 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present ranges from 3.0 mg to 3.5 mg.
19. The pharmaceutical composition of claim 1 , wherein the amount of 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present is about 3.5 mg.
20. The pharmaceutical composition of claim 1 , wherein the amount of 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present is about 4.0 mg.