# US 2008/0187586 A1 · Pharmaceutical Compositions for Glucocorticoid Replacement Therapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2008/0187586 A1 - Document ID: US20080187586A1 - Status: Published application - Kind: A1 - Application number: 11/587,514 - Filed: 2005-04-21 - Published: 2008-08-07 - Earliest claimed: 2004-04-22 - Assignees: Duocort AB - Inventors: Stanko Skrtic; Jorgen Johnsson; Hans Lennernas; Thomas Hedner; Gudmundur Johannsson - Web page: https://patentgrep.com/patent/US20080187586A1 ## CPC - A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone - A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer} - A61K 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)} - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48) - A61P 5/42: for decreasing, blocking or antagonising the activity of mineralocorticosteroids - A61P 5/44: Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61K 9/2031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The invention relates to glucocorticoid replacement therapy and provides pharmaceutical compositions and kits designed to deliver one or more glucocorticoids to a subject in need thereof in a manner that results in serum levels of the glucocorticoid that essentially mimic that of a healthy subject for a clinically relevant period of time. The pharmaceutical composition comprises 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, and the amount of the one or more glucocorticoids of the first part, expressed as hydrocortisone equivalents, is in a range of from about 15 to about 50% of the total hydrocortisone equivalents. The invention also relates to a kit comprising a first and a second component, the first component designed to release one or more glucocorticoids substantially immediately and the second component is designed to release one or more glucocorticoids over an extended period of time of at least 8 hours. The invention also relates to a method for treating diseases requiring glucocorticoid treatment such as in subjects having a glucocorticoid deficiency disorder. In another aspect the invention relates to the use of a first and a second amount of one or more glucocorticoids for the preparation of a pharmaceutical composition or kit for the treatment of a glucocorticoid deficiency disorder. ## Claims ### Claim at position 1 1-110. (canceled) ### Claim 111 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. ### Claim 112 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 50% of the hydrocortisone equivalents of the first part are released within the first 30 min of the dissolution test. ### Claim 113 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 60% of the hydrocortisone equivalents of the first part are released within the first 30 min of the dissolution test. ### Claim 114 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 60% of the hydrocortisone equivalents of the first part are released within the first 20 min of the dissolution test. ### Claim 115 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 70% of the hydrocortisone equivalents of the first part are released within the first 30 min of the dissolution test. ### Claim 116 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 70% of the hydrocortisone equivalents of the first part are released within the first 20 min of the dissolution test. ### Claim 117 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 70% of the hydrocortisone equivalents of the first part are released within the first 30 min of the dissolution test. ### Claim 118 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 80% of the hydrocortisone equivalents of the first part are released within the first 30 min of the dissolution test. ### Claim 119 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 80% of the hydrocortisone equivalents of the first part are released within the first 20 min of the dissolution test. ### Claim 120 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 90% of the hydrocortisone equivalents of the first part are released within the first 20 min of the dissolution test. ### Claim 121 (depends on 111) A pharmaceutical composition according to claim 111, wherein the amount of one or more glucocorticoids of the first part, expressed as hydrocortisone equivalents, is in a range of form about 20 to about 40% such as, e.g. from about 25 to about 35% of the total hydrocortisone equivalents in the composition. ### Claim 122 (depends on 111) A pharmaceutical composition according to claim 111, wherein the second part of one or more glucocorticoids is released over an extended period of time of at least about 10 hours. ### Claim 123 (depends on 122) A pharmaceutical composition according to claim 122, wherein the release is determined in the dissolution test. ### Claim 124 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 50% of the total hydrocortisone equivalents in the composition are released within 10 hours after start of the dissolution test. ### Claim 125 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 50% of the total hydrocortisone equivalents in the composition are released within 8 hours after start of the dissolution test. ### Claim 126 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 80% of the total hydrocortisone equivalents in the composition are released within 24 hours after start of the dissolution test. ### Claim 127 (depends on 111) A pharmaceutical composition according to claim 111, wherein at least about 80% of the total hydrocortisone equivalents in the composition are released within 22 hours after start of the dissolution test. ### Claim 128 (depends on 111) A pharmaceutical composition according to claim 111, wherein from about 3 to about 15% of the hydrocortisone equivalents contained in the second part are released per hour during a time period of from 1 to about 8 hours after start of the dissolution test. ### Claim 129 (depends on 111) A pharmaceutical composition according to claim 111, wherein from about 3 to about 10% of the hydrocortisone equivalents contained in the second part are released per hour during a time period of from 1 to about 8 hours after start of the dissolution test. ### Claim 130 (depends on 111) A pharmaceutical composition according to claim 111, wherein from about 3 to about 15% of the hydrocortisone equivalents contained in the second part are released per hour during a time period of from 1 to about 12 hours after start of the dissolution test. ### Claim 131 (depends on 111) A pharmaceutical composition according to claim 111, wherein from about 3 to about 10% of the hydrocortisone equivalents contained in the second part are released per hour during a time period of from 1 to about 12 hours after start of the dissolution test. ### Claim 132 (depends on 111) A pharmaceutical composition according to claim 111, wherein i) from about 3 to about 15% of the hydrocortisone equivalents contained in the second part are released per hour during a time period of from 1 to about 6 hours, ii) from about 3 to about 10% of the hydrocortisone equivalents contained in the second part are released per hour during a time period of from about 6 to about 10 hours, and iii) from about 3 to about 7.5% of the hydrocortisone equivalents contained in the second part are released per hour during a time period of from about 10 to about 12 hours after start of the dissolution test. ### Claim 133 (depends on 111) A pharmaceutical composition according to claim 111, wherein the amount of hydrocortisone equivalents of the second part of the composition is determined as (Htotal-Hfirst part), wherein Htotal is the total amount of hydrocortisone equivalents released within 24 hours after start of the test and Hfirst part is the amount of hydrocortisone equivalents of the first part of the composition determined. ### Claim 134 (depends on 111) A pharmaceutical composition according to claim 111, wherein the one or more glucocorticoids is selected from the group consisting of hydrocortisone, cortisone, prednisolone, prednisone, methylprednisone, triamcinolone, paramethasone, betamethasone, dexamethasone and fludrocortisone including pharmaceutically acceptable esters, salts and complexes thereof. ### Claim 135 (depends on 111) A pharmaceutical composition according to claim 111, wherein the one or more glucocorticoids of the first and the second part are the same glucocorticoid or a mixture of the same glucocorticoids. ### Claim 136 (depends on 111) A pharmaceutical composition according to claim 111, wherein the one or more glucocorticoids of the first and the second part are different glucocorticoids or a mixture of different glucocorticoids. ### Claim 137 (depends on 111) A pharmaceutical composition according to claim 111, wherein the one or more glucocorticoids of the first part has/have an acceptable taste, is/are tasteless or can be effectively taste-masked. ### Claim 138 (depends on 111) A pharmaceutical composition according to claim 111, wherein the one or more glucocorticoids of the first part is a synthetic glucocorticoid such as, e.g., hydrocortisone 21-succinate, prednisolone, prednisone, methylprednisone, triamcinolone, paramethasone, betamethasone, dexamethasone and fludrocortisone including pharmaceutically acceptable esters, salts and complexes thereof. ### Claim 139 (depends on 111) A pharmaceutical composition according to claim 111, wherein the one or more glucocorticoid of the first part is hydrocortisone or hydrocortisone 21-succinate or a pharmaceutically acceptable salt thereof. ### Claim 140 (depends on 111) A pharmaceutical composition according to claim 111, wherein the one or more glucocorticoid of the second part is hydrocortisone. ### Claim 141 (depends on 111) A pharmaceutical composition according to claim 111 for administration once daily in the morning ### Claim 142 (depends on 111) A pharmaceutical composition according to claim 111, wherein the total amount of hydrocortisone equivalents expressed as hydrocortisone in the composition is from about 1 to about 80 mg. ### Claim 143 (depends on 142) A pharmaceutical composition according to claim 142, wherein the total amount of hydrocortisone equivalents in the composition is from about 1 to 75 mg such as, e.g., from about 1 to about 70 mg, from about 5 to about 60 mg, from about 5 to about 50 mg, from about 5 to about 40 mg or from about 10 to about 30 mg. ### Claim 144 (depends on 111) A pharmaceutical composition according to claim 111 designed for oral administration. ### Claim 145 (depends on 111) A pharmaceutical composition according to claim 111, in the form of a solid dosage form. ### Claim 146 (depends on 145) A pharmaceutical composition according to claim 145, wherein the solid dosage form is selected from the group consisting of granules, bead, pellets and powders. ### Claim 147 (depends on 111) A pharmaceutical composition according to claim 111 in the form of a unit dosage form. ### Claim 148 (depends on 147) A pharmaceutical composition according to claim 147, wherein the unit dosage form is a tablet, capsule or a sachet. ### Claim 149 (depends on 148) A pharmaceutical composition according to claim 148 in the form of a tablet, wherein the one or more glucocorticoids of the first part is comprised in a coating. ### Claim 150 (depends on 147) A pharmaceutical composition according to claim 147, wherein the one or more glucocorticoids of first and the second part are provided as pellets, granules, beads or powders ### Claim 151 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. ### Claim 152 (depends on 151) A kit according to claim 151, wherein at least about 50% of the one or more glucocorticoids of the first component are released within the first 30 min such as e.g., within the first 20 min or within the first 15 min of the dissolution test. ### Claim 153 (depends on 151) A kit according to claim 151, wherein at least about 60% of the one or more glucocorticoids of the first component are released within the first 30 min of the dissolution test. ### Claim 154 (depends on 151) A kit according to claim 151, wherein at least about 60% of the one or more glucocorticoids of the first component are released within the first 20 min of the dissolution test. ### Claim 155 (depends on 151) A kit according to claim 151, wherein at least about 70% of the one or more glucocorticoids of the first component are released within the first 30 min of the dissolution test. ### Claim 156 (depends on 151) A kit according to claim 151, wherein at least about 70% of the one or more glucocorticoids of the first component are released within the first 20 min or within the first 15 min of the dissolution test. ### Claim 157 (depends on 151) A kit according to claim 151, wherein at least about 80% of the one or more glucocorticoids of the first component are released within the first 30 min of the dissolution test. ### Claim 158 (depends on 151) A kit according to claim 151, wherein at least about 80% of the one or more glucocorticoids of the first component are released within the first 20 min of the dissolution test. ### Claim 159 (depends on 151) A kit according to claim 151, wherein at least about 90% of the one or more glucocorticoids of the first component are released within the first 30 min of the dissolution test. ### Claim 160 (depends on 151) A kit according to claim 151, wherein at least about 90% of the one or more glucocorticoids of the first component are released within the first 20 min of the dissolution test. ### Claim 161 (depends on 15) 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. ### Claim 162 (depends on 151) A kit according to claim 151, wherein the one or more glucocorticoids of the second component is released over an extended period of time of at least about 10 hours. ### Claim 163 (depends on 162) A kit according to claim 162, wherein the release is determined in the dissolution test. ### Claim 164 (depends on 151) A kit according to claim 151, wherein from about 3 to about 15% of the one or more glucocorticoids of the second component are released per hour during a time period of from 1 to about 8 hours after start of the dissolution test. ### Claim 165 (depends on 151) A kit according to claim 151, wherein from about 3 to about 10% of the one or more glucocorticoids of the second component are released per hour during a time period of from 1 to about 8 hours after start of the dissolution test. ### Claim 166 (depends on 151) A kit according to claim 151, wherein from about 3 to about 15% of the one or more glucocorticoids of the second component are released per hour during a time period of from 1 to about 10 hours or from about 1 to about 12 hours after start of the dissolution test. ### Claim 167 (depends on 151) A kit according to claim 151, wherein from about 3 to about 10% of the one or more glucocorticoids of the second component are released per hour during a time period of from 1 to about 10 hours or from about 1 to about 12 hours after start of the dissolution test. ### Claim 168 (depends on 151) A kit according to claim 151, wherein i) from about 3 to about 15% of the one or more glucocorticoids of the second component are released per hour during a time period of from 1 to about 6 hours, ii) from about 3 to about 10% of the one or more glucocorticoids of the second component are released per hour during a time period of from about 6 to about 10 hours, and iii) from about 3 to about 7.5% of the one or more glucocorticoids of the second component are released per hour during a time period of from about 10 to about 12 hours after start of the dissolution test. ### Claim 169 (depends on 151) A kit according to claim 151, wherein at least about 25% of the one or more glucocorticoids of the second component are released within 8 hours after start of the dissolution test. ### Claim 170 (depends on 151) A kit according to claim 151, wherein at least about 25% of the one or more glucocorticoids of the second component are released within 7 hours or within 6 hours after start of the dissolution test. ### Claim 171 (depends on 151) A kit according to claim 151, wherein at least about 50% of the one or more glucocorticoids of the second component are released within 12 hours after start of the dissolution test. ### Claim 172 (depends on 151) A kit according to claim 151, wherein at least about 50% of the one or more glucocorticoids of the second component are released within 10 hours or within 9 hours after start of the dissolution test. ### Claim 173 (depends on 151) A kit according to claim 151, wherein at least about 75% of the one or more glucocorticoids of the second component are released within 18 hours after start of the dissolution test. ### Claim 174 (depends on 151) A kit according to claim 151, wherein at least about 75% of the one or more glucocorticoids of the second component are released within 17 hours such as, e.g., within 16 hours, within 15 hours, within 14 hours or within 13 hours after start of the dissolution test. ### Claim 175 (depends on 151) A kit according to claim 151, wherein the amount of one or more glucocorticoids of the second component, expressed as hydrocortisone equivalents, is in a range of from about 50 to about 90% of the total hydrocortisone equivalents in the kit. ### Claim 176 (depends on 151) A kit according to claim 151, wherein the amount of one or more glucocorticoids of the second component, expressed as hydrocortisone equivalents, is in a range of from about 60 to about 80% such as, e.g., from about 65 to about 75% of the total hydrocortisone equivalents in the kit. ### Claim 177 (depends on 151) A kit according to claim 151, wherein each of the first and the second components is in the form of a solid dosage form. ### Claim 178 (depends on 177) A kit according to claim 177, wherein the solid dosage form is selected from the group consisting of granules, beads, pellets and powders. ### Claim 179 (depends on 151) A kit according to claim 151, wherein each of the first and the second components is in the form of a unit dosage form. ### Claim 180 (depends on 179) A kit according to claim 179, wherein the unit dosage form is a tablet, capsule or a sachet. ### Claim 181 (depends on 151) A kit according to claim 151, wherein the first component is in the form of a dosage form that is adapted to administration to or via a mucosa. ### Claim 182 (depends on 181) A kit according to claim 181, wherein the mucosa is selected from the mucosa in the oral cavity, the nasal cavity, the rectum, the gastrointestinal mucosa, or pulmonary, bronchial or respiratory mucosa and epithelia. ### Claim 183 (depends on 182) A kit according to claim 182, wherein the mucosa is the mucosa in the oral cavity. ### Claim 184 (depends on 183) A kit according to claim 183, wherein the first component has an acceptable taste. ### Claim 185 (depends on 151) A kit according to claim 151, wherein the first component is in liquid, semi-solid or solid form. ### Claim 186 (depends on 179) A kit according to claim 179, wherein the first component is in the form of a tablet including a chewable tablet, a suckable tablet, an effervescent tablet, a sublingual tablet, a rapid-burst tablet, immediate release tablets, rapidly dissolvable tablets or the like. ### Claim 187 (depends on 185) A kit according to claim 185, wherein the first component is in the form of a spray, a wafer, a film, a hydrogel, a bioadhesive patch, an inhaler, a powder inhaler, a sachet, a suppository, a clysma, a solution or the like. ### Claim 188 (depends on 151) A kit according to claim 151, wherein the second component is in the form of a solid unit dosage form. ### Claim 189 (depends on 151) A kit according to claim 151, wherein the total amount of hydrocortisone equivalents expressed as hydrocortisone in the kit is from about 1 to about 80 mg. ### Claim 190 (depends on 189) A kit according to claim 189, wherein the total amount of hydrocortisone equivalents in the kit is from about 1 to about 75 mg. ### Claim 191 (depends on 151) A kit according to claim 151, wherein the first and the second component are intended for substantially simultaneous administration ### Claim 192 (depends on 151) A kit according to claim 151, wherein the first and the second component are intended for sequential administration. ### Claim 193 (depends on 151) A kit according to claim 151 further comprising a third component comprising one or more glucocorticoids designed for substantially immediate release of the one or more glucocorticoids. ### Claim 194 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. ### Claim 195 (depends on 194) A method according to claim 194, wherein the first and the second effective amount of the one or more glucocorticoids are administered substantially simultaneously. ### Claim 196 (depends on 194) A method according to claim 194, wherein the first and the second effective amount of the one or more glucocorticoids are administered sequentially. ### Claim 197 (depends on 194) A kit according to claim 194, wherein the serum level obtained within 45 min after administration of the first effective amount of the one or more glucocorticoids is at least about 200 nmol/l. ### Claim 198 (depends on 194) A kit according to claim 194, wherein a serum level of at least about 200 nmol/l is obtained within 30 min or within 20 min after administration of the first effective amount of the one or more glucocorticoids. ### Claim 199 (depends on 194) A kit according to claim 194, wherein the serum level obtained 2 hours after administration of the first effective amount of the one or more glucocorticoids is in a range of from about 200 to about 1000 mmol/l. ### Claim 200 (depends on 199) A method according to claim 199, wherein the serum level obtained is in a range of from about 400 to about 700 nmol/l. ### Claim 201 (depends on 194) A method according to claim 194, wherein the serum level obtained 6 hours after administration of the first effective amount of the one or more glucocorticoids is in a range of from about 200 to about 600 nmol/l. ### Claim 202 (depends on 201) A method according to claim 201, wherein the serum level obtained is in a range of from about 200 to about 400 nmol/l. ### Claim 203 (depends on 194) A method according to claim 194, wherein the serum level obtained 10 hours after administration of the first effective amount of the one or more glucocorticoids is in a range of from about 50 to about 400 nmol/l. ### Claim 204 (depends on 203) A method according to claim 203, wherein the serum level obtained is in a range of from about 100 to about 300 mol/l. ### Claim 205 (depends on 194) A method according to claim 194, wherein the serum level obtained 14 hours after administration of the first effective amount of the one or more glucocorticoids is at the most about 300 nmol/l. ### Claim 206 (depends on 205) A method according to claim 205, wherein the serum level obtained is at the most about 200 nmol/l such as in a range of from about 50 to about 200 nmol/l. ### Claim 207 (depends on 194) A method according to claim 194, wherein the serum level obtained 18 hours after administration of the first effective amount of the one or more glucocorticoids is at the most about 100 nmol/l. ### Claim 208 (depends on 207) A method according to claim 207, wherein the serum level obtained is less than about 50 nmol/l. ### Claim 209 (depends on 194) A method according to claim 194, wherein the first and the second effective amount of the one or more glucocorticoids are administered at wake-up in the morning between about 4 am and noon. ### Claim 210 (depends on 209) A method according to claim 209, wherein the first and the second effective amount of the one or more glucocorticoids are administered at wake-up in the morning between 5 am and noon. ### Claim 211 (depends on 209) A method according to claim 209, wherein the first and the second effective amount of the one or more glucocorticoids are administered to the subject in fasted state. ### Claim 212 (depends on 194) A method according to claim 194, wherein the first and the second effective amount of the one or more glucocorticoids are administered once daily. ### Claim 213 (depends on 194) A method according to claim 194, wherein the serum level obtained in a time period corresponding to from about 0.5-1 to about 6.5-7 hours after administration of the first effective amount of the one or more glucocorticoids essentially mimics the serum level of cortisol of a healthy subject in the morning from 6 am to noon. ### Claim 214 (depends on 194) A method according to claim 194, wherein a 3 hours substantially glucocorticoid-free serum level is obtained daily in a time period of from about 10 pm to about 6 am. ### Claim 215 (depends on 194) A method according to claim 194, wherein the first and the second effective amount are administered in the form of 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. ### Claim 216 (depends on 194) A method according to claim 194, wherein the first and the second effective amount are administered in the form of 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 ### Claim 217 (depends on 111) Use of a first and a second amount of one or more glucocorticoids for the preparation of a pharmaceutical composition as recited in any of claim 111 for the treatment of a glucocorticoid deficiency disorder. ### Claim 218 (depends on 151) Use of a first and a second amount of one or more glucocorticoids for the preparation of a pharmaceutical kit as recited in any of claim 151 for the treatment of a glucocorticoid deficiency disorder. ### Claim 219 (depends on 217) Use according to claim 217, wherein the amount of one or more glucocorticoids provides a serum level.