Pharmaceutical dosage forms comprising 6′-fluoro-(N-methyl- or N,N-dimethyl-)-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine
A pharmaceutical dosage form for administration twice daily, once daily or less frequently, which contains 6′-fluoro-(N-methyl- or N,N-dimethyl)-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine or a physiologically acceptable salt thereof.
1. A monolithic pharmaceutical dosage form in a tablet form for oral administration once daily, wherein the dosage form comprises as pharmacologically active agent the free base of the compound of formula (I′b)
wherein the dose of the pharmacologically active agent is within the range of from 40 μg to 1000 μg; wherein the content of the pharmacologically active agent is at least 0.01 wt.-% and is at most 5 wt.-%, based on the total weight of the dosage form;
wherein the dosage form comprises an anionic surfactant having a HLB value of at least 27; wherein the content of the anionic surfactant is at least 0.2 wt.-%, based on the total weight of the dosage form;
wherein the dosage form comprises a binder;
wherein the dosage form comprises a filler and/or diluent;
wherein the dosage form comprises a lubricant, wherein the content of the lubricant is within the range of from 0.1 wt.-% to 3 wt.-%, based on the total weight of the dosage form;
wherein the dosage form comprises a disintegrant, wherein the content of the disintegrant is within the range of from 0.1 wt.-% to 3 wt.-%, based on the total weight of the dosage form;
wherein the dosage form provides immediate release of the pharmacologically active agent, such that under in vitro conditions in 900 mL artificial gastric juice at pH 1.2 and 37±0.5° C. after 30 minutes according to the paddle method with sinker at 100 rpm it has released at least 50 wt.-% of the pharmacologically active agent originally contained in the dosage form; and
wherein the dosage form provides therapeutic effective pain relief for a period of at least 24 hours when administered orally to a patient in need of such pain relief.
2. The dosage form according to claim 1 , wherein the anionic surfactant has a HLB value of at least 33.
3. The dosage form according to claim 1 , wherein the anionic surfactant is a sulfuric ester.
4. The dosage form according to claim 3 , wherein the sulfuric ester is selected from the group consisting of sodium lauryl sulfate, sodium cetyl sulfate, sodium cetylstearyl sulfate, sodium stearyl sulfate, and the corresponding potassium or calcium salts.
5. The dosage form according to claim 4 , wherein the sulfuric ester is sodium lauryl sulfate.
6. The dosage form according to claim 1 , wherein the binder is selected from the group consisting of gelatin, cellulose, methyl cellulose, polyvinyl pyrrolidone, starch and polyethylene glycol.
7. The dosage form according to claim 6 , wherein the binder is polyvinyl pyrrolidone.
8. The dosage form according to claim 1 , wherein the dosage form comprises 1 to 20 wt.-% of binder(s), based on the total weight of the dosage form.
9. The dosage form according to claim 1 , wherein the filler and/or diluent is at least one member selected from the group consisting of micro-crystalline cellulose, calcium diphosphate, lactose, sucrose, glucose, mannitol, sorbitol, and calcium carbonate.
10. The dosage form according to claim 9 , wherein the filler and/or diluent is micro-crystalline cellulose and lactose.
11. The dosage form according to claim 1 , wherein the content of filler and/or diluent is within the range of from 0.001 wt.-% to 90 wt.-%, based on the total weight of the dosage form.
12. The dosage form according to claim 1 , wherein the lubricant is selected from the group consisting of magnesium stearate, stearic acid and stearin.
13. The dosage form according to claim 1 , wherein the disintegrant is selected from the group consisting of cross-linked sodium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone and sodium starch glycolate.
14. The dosage form according to claim 13 , wherein the dosage form further comprises a film coating.
15. The dosage form according to claim 14 , wherein the film coating is polyvinyl alcohol-based.
16. The dosage form according to claim 1 , which under in vitro conditions in 900 mL artificial gastric juice at pH 1.2 and 37±0.5° C. after 30 minutes according to the paddle method with sinker at 100 rpm has released at least 80 wt.-% of the pharmacologically active agent originally contained in the dosage form.
17. A method of treating pain in a patient in need thereof, said method comprising orally administering to said patient a dosage form according to claim 1 at a frequency of once daily.