Claims for Patent: 11,007,156

Summary for Patent: 11,007,156

Title:	Prolonged release pharmaceutical composition containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol
Abstract:	A pharmaceutical formulation for prolonged release of the active ingredient 3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol or a pharmaceutically acceptable salt thereof in a matrix containing between 1 and 80 wt. % of at least one pharmaceutically acceptable hydrophilic or hydrophobic polymer as a matrix forming agent and exhibiting in vivo the following release rate: 3 to 35% by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours; 5 to 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 1 hour; 10 to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 2 hours; 15 to 82% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 3 hours; 30 to 97% by weight 3-(3-dimethylaminol-1-ethyl-2-methyl-propyl)phenol released after 6 hours; more than 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 12 hours; more than 70% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 18 hours, and more than 80% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours.
Inventor(s):	Johannes Bartholomaeus, Iris Ziegler
Assignee:	Gruenenthal GmbH
Application Number:	US16/600,974
Patent Claims:	1. A slow-release oral pharmaceutical formulation comprising 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof as active ingredient in a matrix, wherein the matrix comprises 1 to 40% by weight of one or more pharmaceutically acceptable matrix forming agents selected from the group consisting of hydroxypropylmethyl celluloses (HPMC), hydroxyethyl celluloses, hydroxypropyl celluloses (HPC), methyl celluloses, ethyl celluloses and carboxymethyl celluloses, wherein the oral pharmaceutical formulation has the following in vitro release rate, measured by the Ph. Eur. Paddle Method at 75 rpm in a buffer (to Ph. Eur.) at a pH of 6.8 at 37° C. and detected using a UV spectrometer: 3 to 35% by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours, 5 to 50% by weight 3-(3-dimethylaminol-ethyl-2-methyl-propyl)phenol released after 1 hour, 10 to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 2 hours, 15 to 82% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 3 hours, 30 to 97% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 6 hours, more than 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 12 hours, more than 70% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 18 hours, and more than 80% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours, wherein a peak plasma level of the active ingredient is obtained in vivo, according to the plasma concentration/time graph, of between about 2 to about 10 hours after administration of the formulation, and the matrix forming agents have a viscosity of 3,000 to 150,000 mPas in a 2% by weight solution at 20° C. 2. A pharmaceutical formulation according to claim 1, wherein the matrix forming agents have a viscosity of 10,000 to 150,000 mPa·s in a 2% by weight solution at 20° C. 3. A pharmaceutical formulation according to claim 1, wherein the matrix forming agents have a viscosity of 50,000 to 150,000 mPa·s in a 2% by weight solution at 20° C. 4. A pharmaceutical formulation according to claim 1, wherein the matrix forming agent comprises at least one substance selected from the group consisting of hydroxypropylmethyl celluloses, hydroxyethyl celluloses, and hydroxypropyl celluloses. 5. A pharmaceutical formulation according to claim 1, wherein said formulation contains from 0.5 to 85% by weight active ingredient and from 8 to 40% by weight matrix forming agents. 6. A pharmaceutical formulation according to claim 1, wherein said formulation comprises from 3 to 70% by weight active ingredient and from 10 to 35% by weight matrix forming agents. 7. A pharmaceutical formulation according to claim 6, wherein said formulation comprises from 8 to 66% by weight active ingredient and from 10 to 30% by weight matrix forming agents. 8. A pharmaceutical formulation according to claim 1, wherein the peak plasma level of the active ingredient is obtained in vivo 3.5 to 6 hours after administration of the formulation. 9. A pharmaceutical formulation according to claim 1, wherein the active ingredient comprises (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof. 10. A pharmaceutical formulation according to claim 1, wherein the active ingredient comprises (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof. 11. A tablet for twice daily oral administration of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, said tablet containing a pharmaceutical formulation according to claim 1. 12. A slow-release oral pharmaceutical formulation comprising 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof as active ingredient in a matrix, wherein the matrix comprises 1 to 40% by weight of one or more pharmaceutically matrix forming agents selected from the group consisting of hydroxypropylmethyl celluloses (HPMC), hydroxyethyl celluloses, hydroxypropyl celluloses (HPC), methyl celluloses, ethyl celluloses and carboxymethyl celluloses, wherein a peak plasma level of the active ingredient is obtained in vivo, according to the plasma concentration/time graph, of between about 2 to about 10 hours after administration of the formulation, and the matrix forming agents have a viscosity of 3,000 to 150,000 mPa·s in a 2% by weight aqueous solution at 20° C. 13. A pharmaceutical formulation according to claim 12, wherein the matrix forming agents have a viscosity of 10,000 to 150,000 mPa·s in a 2% by weight solution at 20° C. 14. A pharmaceutical formulation according to claim 12, wherein the matrix forming agents have a viscosity of 50,000 to 150,000 mPa·s in a 2% by weight solution at 20° C. 15. A pharmaceutical formulation according to claim 12, wherein the matrix forming agent comprises at least one substance selected from the group consisting of hydroxypropylmethyl celluloses, hydroxyethyl celluloses, and hydroxypropyl celluloses. 16. A pharmaceutical formulation according to claim 12, wherein said formulation contains from 0.5 to 85% by weight active ingredient and from 8 to 40% by weight matrix forming agents. 17. A pharmaceutical formulation according to claim 12, wherein said formulation comprises from 3 to 70% by weight active ingredient and from 10 to 35% by weight matrix forming agents. 18. A pharmaceutical formulation according to claim 17, wherein said formulation comprises from 8 to 66% by weight active ingredient and from 10 to 30% by weight matrix forming agents. 19. A pharmaceutical formulation according to claim 12, wherein the peak plasma level of the active ingredient is obtained in vivo 3.5 to 6 hours after administration of the formulation. 20. A pharmaceutical formulation according to claim 12, wherein the active ingredient comprises (+)-(1S, 2 S)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof. 21. A pharmaceutical formulation according to claim 12, wherein the active ingredient comprises (−)-(1R,2R)-3-(3-dimethyl amino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof. 22. A tablet for twice daily oral administration of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, said tablet containing a pharmaceutical formulation according to claim 12. 23. A method of treating pain in a patient in need thereof comprising administering to said patient twice daily a tablet according to claim 11. 24. A method of treating pain in a patient in need thereof comprising administering to said patient twice daily a tablet according to claim 22. 25. A pharmaceutical formulation according to claim 1, wherein the matrix forming agent is hydroxypropylmethylcellulose having a viscosity of ca. 100,000 mPa·s in a 2 wt % solution at 20° C. 26. A pharmaceutical formulation according to claim 12, wherein the matrix forming agent is hydroxypropylmethylcellulose having a viscosity of ca. 100,000 mPa·s in a 2 wt % solution at 20° C.