Patent EA-004068-B1 (EA)
Title: Controlled-release pharmaceutical formulations containing a cgmp pde-5 inhibitor
Inventor: KING ELIZABETH
IPC: A61P15/10
Filed: 1999-10-04
Abstract: 1. A controlled-release formulation for oral administration containing a cGMP PDE-5 inhibitor (cGMP -cyclic guanozine -3`,5`-monophosphate). 2. A formulation as claimed in claim 1, wherein up to 75% by weight of the cGMP PDE-5 inhibitor is released from the formulation into the gastrointestinal tract after a period of time in the range 1-24 hours following administration. 3. A formulation as claimed in claim 1 or claim 2, wherein the cGMP PDE-S inhibitor is embedded in a matrix from which it is released by diffusion or erosion. 4. A formulation as claimed in any one of claims 1 to 3, wherein the cGMP PDE 5 inhibitor is present in a core which is coated with a release rate-controlling membrane. 5. A formulation as claimed in any one of claims 1 to 4, which comprises a core containing the cGMP PDE-5 inhibitor and an outer coating impermeable to the cGMP PDE-5 inhibitor. the outer coating having an aperture for release of the cGMP PDE-5 inhibitor. 6. A formulation as claimed in any one of the preceding claims, wherein the cGMP PDE-5 inhibitor is sildenafil, or a pharmaceutically acceptable salt thereof. 7. A formulation as claimed in claim 6, wherein the cGMP PDE-5 inhibitor is sildenafil citrate. 8. A formulation as claimed in claim 3, which also contains hydroxypropylmethyl cellulose. 9. A formulation as claimed in claim 3 or claim 8, which also contains a buffering agent. 10. A formulation as claimed in claim 8 or claim 9, wherein the hydroxypropylmethyl cellulose has a number average molecular weight in the range 80,000-250,000. 11. A formulation as claimed in any one of claims 8 to 10, wherein the hydroxypropylmethyl cellulose has a degree of methyl substitution in the range 19-30%. 12. A formulation as claimed in any one of claims 8 to 11, wherein the hydroxypropylmethyl cellulose has a degree of hydroxy substitution in the range 7-12%. 13. A formulation as claimed in any one of claims 8 to 12, wherein the hydroxypropylmethyl cellulose makes up 10-50% by weight of the formulation. 14. A formulation as claimed in claim 4, wherein a multiplicity of coated cores is present. 15. A formulation as claimed in claim 14, wherein the core also includes a buffering agent. 16. A formulation as claimed in claim 4 claim 14 or claim 15, wherein the release ratecontrolling membrane comprises an ammonia methacrylate copolymer and a plasticizer. 17. A formulation as claimed in any one of the preceding claims, which is provided with a cosmetic coating. 18. A formulation as claimed in any one of the preceding claims, wherein the cGMP PDE-5 inhibitor makes up 5-50% by weight of the formulation. 19. A formulation as claimed in any one of the preceding claims, characterized in that the rate at which the cGMP PDE-5 inhibitor is released therefrom is substantially independent of the pH of the surroundings. 20. A process for the production of a formulation as claimed in claim 3, which includes mixing the cGMP PDE-5 inhibitor with a matrix material, and pressing into tablets. 21. A process for the production of a formulation as claimed in claim 4, which includes forming a core comprising the cGMP PDE-5 inhibitor and, optionally, the matrix substance and then coating the core with a release rate-controlling membrane. 22. A process for the production of a formulation as claimed in claim 4, which includes forming a core comprising the cGMP PDE-5 inhibitor and, optionally, the matrix substance and then coating the core with a coating impermeable to the cGMP PDE-5 inhibitor; and forming the aperture in said coating. 23. Use of a cGMP PDE-5 inhibitor in the manufacture of a formulation of claim 1 for the treatment or prevention of sexual dysfunction, characterized in that, following administration, the. formulation releases the inhibitor over or after a sustained period of time. 24. Use of a cGMP PDE-5 inhibitor in the manufacture of a formulation of claim 1 for improving sexual dysfunction in a mammal. 25. The use of claim 23 or claim 24, characterized in that, following administration, the mammal's sexual function is substantially improved for or after a sustained period of time. 26. Use of a cGMP PDE-5 inhibitor in the manufacture of a formulation of claim 1 for increasing the probability of a nocturnal erection in a male mammal. 27. A dual release formulation for oral administration having: a) a first portion comprising a controlled-release formulation comprising a cGMP PDE-5 inhibitor and b) a second portion comprising a cGMP PDE-5 inhibitor in immediate release form. 28. Products containing a controlled-release formulation as defined in claim 1, and a cGMP PDE-5 inhibitor in immediate release form, as a combined preparation for simultaneous, separate or sequential use in the treatment or prevention of sexual dysfunction. 29. A controlled-release formulation for oral administration containing a cGMP PDE-5 inhibitor provided that it consists substantially of sildenafil, low molecular polyetheleneoxide, hydroxypropylmethyl cellulose, excipients used in tabletting, and, optionally one or more intestinal soluable polymer.