Patent EA-002481-B1 (EA)
Title: Solubilized sertraline-based compositions
Inventor: FRIESEN DWAYNE THOMAS
IPC: A61K9/20
Filed: 1998-06-15
Abstract: 1. A composition of matter comprising sertraline or a pharmaceutically acceptable salt thereof and an amount of a solubilizing agent sufficient to produce a concentration of dissolved sertraline in a use environment containing chloride ions which is 1.5 times higher than the concentration effected by a comparative composition of matter identical thereto but for the inclusion of said solubilizing agent, provided said solubilizing agent is not alginic acid, sodium citrate, calcium carbonate, a polyethylene glycol having a molecular weight greater than 3350, sesame oil, peanut oil, sodium lauril sulfate. 2. A composition of matter as defined in claim 1, wherein said use environment is the Gl tract. 3. A composition of matter as defined in claim 1, wherein said use environment is an aqueous chloride ion-containing test medium. 4. A composition of matter as defined in claim 3, wherein said use environment is 0.075 M sodium chloride. 5. A composition of matter as defined in claim 1, which is an immediate release dosage form. 6. A composition of matter as defined in claim 1, which is a controlled release dosage form. 7. A composition of matter as defined in claim 1, wherein said solubilizing agent is selected from: 1) organic acids and organic acid salts; 2) partial glycerides; 3) glycerides; 4) glyceride derivatives; 5) polyethylene glycol esters; 6) polypropylene glycol esters; 7) polyhydric alcohol esters;  8) polyoxyethylene ethers; 9) sorbitan esters; 10) polyoxyethylene sorbitan esters; and 11) carbonate salts. 8. A composition of matter as defined in claim 4, wherein the amount of said solubilizing agent is sufficient to maintain, for at least 2 hours, the concentration of dissolved sertraline at a level which is at least 1.5 times higher than the concentration of sertraline produced by a comparative composition of matter identical thereto but for the inclusion of said solubilizing agent. 9. A composition as defined in claim 1, wherein said solubilizing agent is selected from aspartic acid, glyceryl monocaprylate, glyceryl monolaurate, calcium acetate, ascorbic acid, citric acid, glutamic acid, and calcium carbonate. 10. A composition of matter comprising sertraline or a pharmaceutically acceptable salt thereof and an amount of a solubilizing agent sufficient to produce and to maintain, for at least 2 hours in 0.075M sodium chloride, a concentration of dissolved sertraiine which is at least 1.5 times higher than the concentration effected by a comparative composition of matter identical thereto but for the inclusion of said solubilizing agent, provided said solubilizing agent is not alginic acid, sodium citrate, calcium carbonate, a polyethylene glycol having a molecular weight greater than 3350, sesame oil, peanut oil, sodium lauril sulfate. 11. A composition of matter as defined in claim 10, which is an immediate release dosage form. 12. A composition of matter as defined in claim 10, which is a controlled release dosage form. 13. A composition of matter as defined in claim 10, wherein said solubilizing agent is selected from: 1) organic acids and organic acid salts; 2) partial glycerides;  3) glycerides; 4) glyceride derivatives; 5) polyethylene glycol esters; 6) polypropylene glycol esters; 7) polyhydric alcohol esters; 8) polyoxyethylene ethers; 9) sorbitan esters; 10) polyoxyethylene sorbitan esters; and 11) carbonate salts. 14. A composition as defined in claim 10, wherein said solubilizing agent is selected from aspartic acid, glyceryl monocaprylate, glyceryl monolaurate, calcium acetate, ascorbic acid, citric acid, glutamic acid, and calcium carbonate. 15. A composition of matter comprising sertraline or a pharmaceutically acceptable salt thereof and an amount of a solubiiizing agent sufficient to effect, in vivo, a Cmax and/or an AUC which is greater by at least 10% than the Cmax and/or AUC effected by a comparative composition of matter identical thereto but for the inclusion of said solubilizing agent, provided said solubilizing agent is not alginic acid, sodium citrate, calcium carbonate, a polyethylene glycol having a molecular weight greater than 3350, sesame oil, peanut oil, sodium lauril sulfate. 16. A composition as defined in claim 15, wherein said Cmax and/or AUC effected by said solubilizing agent-containing composition is at least 15% higher than the corresponding Cmax and/or AUC effected by said comparative composition. 17. A composition as defined in claim 16, wherein said Cmax, and/or AUC effected by said solubilizing agent-containing composition is at least 20% higher than the corresponding Cmax and/or AUC effected by said comparative composition. 18. A composition of matter as defined in claim 15, which is an immediate release dosage form. 19. A composition of matter as defined in claim 15, which is a controlled release dosage form. 20. A composition of matter as defined in claim 15, wherein said solubilizing agent is selected from: 1) organic acids and organic acid salts; 2) partial glycerides; 3) glycerides; 4) glyceride derivatives; 5) polyethylene glycol esters; 6) polypropylene glycol esters; 7) polyhydric alcohol esters; 8) polyoxyethylene ethers;  11) carbonate salts. 9) sorbitan esters; 10) polyoxyethylene sorbitan esters; and 11) carbonate salts. 21. A composition of matter as defined in claim 15, wherein said solubilizing, agent is selected from aspartic acid, glyceryl monocaprylate, glyceryl monolaurate, calcium acetate, ascorbic acid, citric acid, glutamic acid, and calcium carbonate. 22. A method of increasing the solubility of sertraline in an aqueous chloride ion-containing use environment, comprising administering said sertraline to said use environment in a composition of matter additionally comprising a solubilizing agent, provided said solubilizing agent is not alginic acid, sodium citrate, calcium carbonate, a polyethylene glycol having a molecular weight greater than 3350, sesame oil, peanut oil, sodium lauril sulfate. 23. A method as defined in claim 22, wherein the concentration of dissolved sertraline in said use environment also containing said solubilizer is at least 1.5-fold higher than the concentration of sertraline effected by a comparative composition identical to said solubilizing agent-containing composition except for the inclusion of said solubilizing agent. 24. A method as defined in claim 22, wherein said use environment is the GI tract. 25. A method as defined in claim 22, wherein said use environment is an aqueous chloride ion-containing test medium. 26. A method as defined in claim 25, wherein said medium is 0.075 M sodium chloride. 27. A method as defined in claim 22, wherein said composition of matter is in the form of an immediate release dosage form. 28. A method as defined in claim 22, wherein said composition of matter is in the form of a controlled release dosage form. 29. A method as defined in claim 22, wherein said solubiiizing agent is selected from: 1) organic acids and organic acid salts; 2) partial glycerides; 3) glycerides; 4) glyceride derivatives; 5) polyethylene glycol esters; 6) polypropylene glycol esters; 7) polyhydric alcohol esters; 8) polyoxyethylene ethers; 9) sorbitan esters; and 10) polyoxyethylene sorbitan esters; 11) carbonate salts.