Tigecycline compositions and methods of preparation
View Patent ↗The present invention relates to novel tigecycline compositions with improved stability in both solid and solution states and processes for making these compositions. These compositions comprise tigecycline, a suitable carbohydrate, and an acid or buffer.
1. A composition comprising tigecycline, lactose, and an acid, wherein the molar ratio of tigecycline to lactose is between about 1:1.6 to about 1:3.3, and the pH of the composition in a solution is between about 4.0 and about 5.0, wherein the acid is hydrochloric acid, and the composition further comprises tigecycline epimer in an amount that is not more than 2.56% as measured after storage of the composition at about 40° C. and 75% relative humidity for not more 39 days.
2. The composition of claim 1 , wherein the composition is lyophilized.
3. The composition according to claim 1 further comprising a pharmaceutically acceptable diluent.
4. The composition according to claim 3 , wherein the pharmaceutically acceptable diluent is water, a saline, Lactated Ringer's Injection solution, or dextrose solution.
5. The composition of claim 1 , wherein the pH of the composition in a solution is between 4.2 and about 4.8.
6. A process for preparing a tigecycline composition comprising combining lactose with tigecycline and water to form a solution; reducing the pH of the solution with hydrochloric acid to between about 4.0 and about 5.0; and lyophilizing the solution to dryness to prepare a lyophilized composition;
wherein the lactose is capable of reducing epimer formation of tigecycline whereby the lyophilized composition further comprises tigecycline epimer in an amount that is not more than 2.56% as measured after storage of the lyophilized composition at about 40° C. and 75% relative humidity for not more 39 days, and the molar ratio of tigecycline to lactose is between about 1:1.6 to about 1:3.3.
7. The process of claim 6 further comprising combining the composition with a saline, Lactated Ringer's Injection solution or dextrose solution.
8. The process of claim 6 , wherein a solid is formed.
9. The process of claim 6 , wherein the pH of the solution is reduced to between about 4.2 and about 4.8.