Pharmaceutical Compositions for Glucocorticoid Replacement Therapy

A pharmaceutical composition comprising one or more glucocorticoids, wherein a first part of one or more glucocorticoids is substantially immediately released and a second part of one or more glucocorticoids is released over an extended period of time of at least about 8 hours.

• the amount of the one or more glucocorticoids of the first part, expressed as hydrocortisone equivalents, being in a range of from about 15 to about 50% of the total hydrocortisone equivalents in the composition and determined as the amount release 1 hour after start of testing to the composition in an in vitro dissolution test according to USP employing USP Dissolution Apparatus No. 2 (paddle), 50 rpm and simulated intestinal fluid without enzymes as dissolution medium,
• wherein at least about 50% of the hydrocortisone equivalents of the first part is released within the first 45 min of the dissolution test.

A kit comprising

• i) a first component comprising one or more glucocorticoids, the first component being designed for substantially immediate release of the one or more glucocorticoids and the amount of one or more glucocorticoids of the first component, expressed as hydrocortisone equivalents, being in a range of from about 10 to about 50% of the total hydrocortisone equivalents in the kit
• ii) a second component comprising one or more glucocorticoids, the second component being designed for extended release of the one or more glucocorticoids over a period of time of at least about 8 hours.
• wherein at least about 50% of the one or more glucocorticoids of the first component are released within the first 45 min of a dissolution test employing USP Dissolution Apparatus No. 2 (paddle), 50 rpm and simulated intestinal fluid without enzymes as dissolution medium.

A kit according to claim 15, wherein the amount of one or more glucocorticoids of the first component, expressed as hydrocortisone equivalents, is in a range of from about 15 to about 50% such as, e.g., from about 20 to about 40% or from about 25 to about 35% of the total hydrocortisone equivalents in the kit.

A method for treating a subject suffering from a glucocorticoid deficiency disorder, the method comprises administering to the subject a first effective amount of one or more glucocorticoids that leads to a fast rise in the glucocorticoid serum level and a second effective amount of one or more glucocorticoids that leads to an effective serum concentration of the one or more glucocorticoids during an extended period of time of at least about 8 hours.