Claims for Patent: 10,166,190

Summary for Patent: 10,166,190

Title:	Stabilized tacrolimus composition
Abstract:	The invention relates to a stable pharmaceutical composition comprising comprising a solid dispersion of tacrolimus in a vehicle further comprising a stabilizing agent capable of providing a pH below 7 in the composition, as measured after re-dispersion in water, and preventing or reducing the formation upon storage of major degradation products of tacrolimus, in particular the 8-epitacrolimus.
Inventor(s):	Skak; Nikolaj (Virum, DK), Holm; Per (Vanlose, DK)
Assignee:	VELOXIS PHARMACEUTICALS A/S (Copenhagen, DK)
Application Number:	15/405,879
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,166,190
Patent Claims:	1. A sustained release tablet comprising (i) a dispersion of tacrolimus, (ii) 8-epitacrolimus, and (iii) a metal chelating agent that is an organic acid, wherein the tacrolimus is the sole active ingredient in the tablet and the tablet comprises a sufficient amount of the metal chelating agent such that the tablet comprises less than 0.5% by weight of the 8-epitacrolimus after 12 weeks of storage at 25.degree. C. and 60% relative humidity, based upon 100% total weight of tacrolimus. 2. A sustained release tablet comprising (i) a dispersion of tacrolimus, (ii) 8-epitacrolimus, and (iii) a metal chelating agent that is an organic acid, wherein the tacrolimus is the sole active ingredient in the tablet and the tablet comprises a sufficient amount of the metal chelating agent such that the tablet comprises less than 0.5% by weight of the 8-epitacrolimus after 10 months of storage at 25.degree. C. and 60% relative humidity, based upon 100% total weight of tacrolimus. 3. A sustained release tablet comprising a solid dispersion of tacrolimus in a mixture of a vehicle and a metal chelating agent that is an organic acid, wherein the tacrolimus is the sole active ingredient in the tablet and the tablet contains a sufficient amount of the metal chelating agent such that the tablet comprises (a) no more than 0.5% by weight 8-epitacrolimus after storage at 40.degree. C. at 75% relative humidity for 5 weeks compared to the tablet prior to storage, or (b) no more than 0.2% by weight 8-epitacrolimus after storage at 25.degree. C. at 60% relative humidity for 5 weeks compared to the tablet prior to storage, based upon 100% total weight of tacrolimus. 4. A stabilized sustained release tablet comprising (A) a solid dispersion of tacrolimus, (B) 8-epitacrolimus, and (C) a metal chelating agent that is an organic acid, wherein (i) the tacrolimus is the sole active ingredient in the tablet and (ii) the tablet contains a sufficient amount of the metal chelating agent such that the tablet comprises no more than 0.5% by weight of the 8-epitacrolimus after storage at 25.degree. C. at 60% relative humidity for 5 weeks, based upon 100% total weight of tacrolimus. 5. The sustained release tablet of claim 1, wherein the tablet has a pH of 2.5 to 4 as measured after re-dispersing the tablet in water. 6. The sustained release tablet of claim 2, wherein the tablet has a pH of 2.5 to 4 as measured after re-dispersing the tablet in water. 7. The sustained release tablet of claim 3, wherein the tablet has a pH of 2.5 to 4 as measured after re-dispersing the tablet in water. 8. The sustained release tablet of claim 4, wherein the tablet has a pH of 2.5 to 4 as measured after re-dispersing the tablet in water. 9. The sustained release tablet of claim 1, wherein the dispersion of tacrolimus comprises tacrolimus dispersed in a vehicle, and the metal chelating agent is dissolved in the vehicle. 10. The sustained release tablet of claim 2, wherein the dispersion of tacrolimus comprises tacrolimus dispersed in a vehicle, and the metal chelating agent is dissolved in the vehicle. 11. The sustained release tablet of claim 3, wherein the metal chelating agent is dissolved in the vehicle. 12. The sustained release tablet of claim 4, wherein the dispersion of tacrolimus comprises tacrolimus dispersed in a vehicle, and the metal chelating agent is dissolved in the vehicle. 13. The sustained release tablet of claim 1, wherein the metal chelating agent is oxalic acid. 14. The sustained release tablet of claim 2, wherein the metal chelating agent is oxalic acid. 15. The sustained release tablet of claim 3, wherein the metal chelating agent is oxalic acid. 16. The sustained release tablet of claim 4, wherein the metal chelating agent is oxalic acid.