Stable formulations for parenteral injection of peptide drugs

A stable formulation for parenteral injection, comprising:

• (a) glucagon, wherein the glucagon has been dried in a non-volatile buffer, and wherein the dried glucagon has a pH memory that is about equal to the pH of the glucagon in the non-volatile buffer selected from a glycine buffer, a citrate buffer, a phosphate buffer, and mixtures thereof, wherein the pH memory of the dried glucagon is from about 2.0 to about 3.0;
• and
• (b) an aprotic polar solvent selected from dimethylsulfoxide (DMSO), n-methyl pyrrolidone (NMP), ethyl acetate, and mixtures thereof;
• wherein the moisture content of the formulation is less than 1%, and wherein the dried glucagon maintains the pH memory that is about equal to the pH of the glucagon in the non-volatile buffer when the dried glucagon is reconstituted in the aprotic polar solvent.

A stable formulation for parenteral injection, comprising:

• (a) a first peptide or a salt thereof, wherein the first peptide has been dried in a first non-volatile buffer, and wherein the first dried peptide has a first pH memory that is about equal to the pH of the first peptide in the first non-volatile buffer;
• (b) a second peptide or a salt thereof, wherein the second peptide has been dried in a second non-volatile buffer, and wherein the second dried peptide has a second pH memory that is about equal to the pH of the second peptide in the second non-volatile buffer;
• and
• (c) an aprotic polar solvent;
• wherein the moisture content of the formulation is less than 5%, wherein the first dried peptide maintains the first pH memory that is about equal to the pH of the first peptide in the first non-volatile buffer when the first dried peptide is reconstituted in the aprotic polar solvent, and wherein the second dried peptide maintains the second pH memory that is about equal to the pH of the second peptide in the second non-volatile buffer when the second dried peptide is reconstituted in the aprotic polar solvent.

A stable formulation for parenteral injection, comprising:

• (a) insulin, wherein the insulin has been dried in a first non-volatile buffer selected from a glycine buffer, a citrate buffer, a phosphate buffer, and mixtures thereof, and wherein the dried insulin has a first pH memory that is about equal to the pH of the insulin in the first non-volatile buffer, wherein the first pH memory is from about 1.5 to about 2.5 or from about 6.0 to about 8.0;
• (b) pramlintide, wherein the pramlintide has been dried in a second non-volatile buffer selected from a glycine buffer, a citrate buffer, a phosphate buffer, and mixtures thereof, and wherein the dried pramlintide has a second pH memory that is about equal to the pH of the pramlintide in the second non-volatile buffer, wherein the second pH memory is from about 3.0 to about 5.0;
• and
• (c) an aprotic polar solvent selected from dimethylsulfoxide (DMSO), n-methyl pyrrolidone (NMP), ethyl acetate, and mixtures thereof;
• wherein the moisture content of the formulation is less than 1%, wherein the dried insulin maintains the first pH memory that is about equal to the pH of the insulin in the first non-volatile buffer when the dried insulin is reconstituted in the aprotic polar solvent, and wherein the dried pramlintide maintains the second pH memory that is about equal to the pH of the pramlintide in the second non-volatile buffer when the dried pramlintide is reconstituted in the aprotic polar solvent.

A method of making a stable formulation for parenteral injection, the method comprising:

• (a) drying a mixture comprising a peptide or salt thereof in a non-volatile buffer to a dried peptide powder, wherein the dried peptide powder has a pH memory that is about equal to the pH of the peptide in the non-volatile buffer;
• and
• (b) reconstituting the dried peptide powder in an aprotic polar solvent;
• wherein the moisture content of the formulation is less than 5%, and wherein the dried peptide powder maintains the pH memory that is about equal to the pH of the peptide in the non-volatile buffer when the dried peptide powder is reconstituted in the aprotic polar solvent.

A method of making a stable formulation for parenteral injection, the method comprising:

• (a) drying a first mixture comprising a first peptide or salt thereof in a first non-volatile buffer to a first dried peptide powder, wherein the first dried peptide powder has a first pH memory that is about equal to the pH of the first peptide in the first non-volatile buffer;
• (b) drying a second mixture comprising a second peptide or salt thereof in a second non-volatile buffer to a second dried peptide powder, wherein the second dried peptide powder has a second pH memory that is about equal to the pH of the second peptide in the second non-volatile buffer;
• and
• (c) reconstituting the first dried peptide powder and the second dried peptide powder in an aprotic polar solvent;
• wherein the moisture content of the formulation is less than 5%, wherein the first dried peptide powder maintains the first pH memory that is about equal to the pH of the first peptide in the first non-volatile buffer when the first dried peptide powder is reconstituted in the aprotic polar solvent, and wherein the second dried peptide powder maintains the second pH memory that is about equal to the pH of the second peptide in the second non-volatile buffer when the second dried peptide powder is reconstituted in the aprotic polar solvent.