Sustained release parenteral formulation used for ionic peptide drugs, useful e.g. for treating hormone dependent diseases, comprises active agent mixed with aqueous salt solution at specific concentrations

摘要

Pharmaceutical formulation (A) comprises at least one ionic peptide active agent (I) in a predetermined amount, mixed with an aqueous solution of an inorganic or acetate salt (II) of a predetermined concentration, where the amount and concentration values are determined by specific test procedures based on blood plasma levels and times to reach these levels. Pharmaceutical formulation (A) comprises at least one ionic peptide active agent (I) in a predetermined amount Xoptimum (in mg of (I) per ml of (A)), mixed with an aqueous solution of an inorganic or acetate salt (II) of a predetermined concentration Yoptimum (in % w/v). The value of Xoptimum is determined by supplying various amounts Xn (n being 1 or more) of (I), as a mixture with isotonic aqueous mannitol solution to a test system and selecting the amount Xoptimum giving the best blood plasma (I) levels regarding Cmax (maximum blood plasma concentration) and tmax (time to reach Cmax). The value of Yoptimum is determined by supplying an amount Xoptimum of (I), as a mixture with aqueous solutions containing various amounts Yn (n being 1 or more) of (I) to a test system and selecting the concentration Yoptimum giving the highest plasma (I) concentration Cactive, where Cactive is between Cmax and Cminimum (Cmin being the lowest plasma concentration at which (I) shows pharmaceutical activity). (II) also has an effect on the time period tactive to reach the highest plasma concentration, so that tactive is more than tmax. Independent claims are included for: (1) the preparation of (A); and (2) a kit for the production of (A), which comprises a fixed amount (X mg per mol of final formulation) of (I) in lyophilized form and an aqueous solution of a fixed amount (Y% w/v) of (II).