Claims:We claim:
1. A multi-dose fludrocortisone oral solution comprising of fludrocortisone or a pharmaceutically acceptable salt thereof, at least one vehicle, at least one preservative, at least one antioxidant, at least one buffering agent and at least one flavoring agent; wherein the pH of the oral solution is about 3 to 9 and the concentration of fludrocortisone in the oral solution is about 0.05 to 0.3 mg/ml.

2. The fludrocortisone oral solution as claimed in claim 1; wherein the vehicle is selected from the group comprising of butylene glycol, polyethylene glycol, propylene glycol, glycerin monostearate, sorbitol, ethanol and propylene glycol or a combination thereof.

3. The fludrocortisone oral solution as claimed in claim 1; wherein the preservative is selected from the group comprising of benzalkonium chloride, benzoic acid, benzyl alcohol, boric acid, bronopol, butylated hydroxyanisole, butylene glycol, butylparaben, calcium acetate, cationic, and bentonite, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, dimethyl ether, ethylparaben, hexetidine, imidurea, inactivation by magnesium trisilicate, isopropyl alcohol, lactic acid, methylparaben, monothioglycerol, benzalkonium chloride, benzoic acid, benzyl alcohol, boric acid, bronopol, butylated hydroxyanisole, butylene glycol, butylparaben, calcium acetate, cationic, and bentonite, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, dimethyl ether, ethylparaben, hexetidine, imidurea, inactivation by magnesium trisilicate, isopropyl alcohol, lactic acid, methylparaben and monothioglycerol or a combination thereof.

4. The fludrocortisone oral solution as claimed in claim 1; wherein the antioxidant is selected from the group comprising of Propyl & octyl esters of gallic acid, tocopherols or vitamin E, sodium sulfite, ascorbic acid (vit. C), alpha tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, carbon dioxide, chelating agents, citric acid monohydrate, erythorbic acid, ethyl oleate, fumaric acid, malic acid, methionine, monothioglycerol, phosphoric acid, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, Sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium sulfite, sodium thiosulfate and sulfur dioxide or a combination thereof.

5. The fludrocortisone oral solution as claimed in claim 1; wherein the buffering agent is selected from the group comprising of adipic acid, tartaric acid, boric acid, citric acid monohydrate, HCL, maleic acid, adipic acid, ammonia solution, boric acid, calcium carbonate, calcium hydroxide, calcium lactate, calcium phosphate, tribasic, dibasic sodium phosphate, diethanolamine, methionine, monobasic sodium phosphate, monoethanolamine, monosodium glutamate, phosphoric acid, potassium citrate, sodium acetate, sodium bicarbonate, sodium borate, sodium carbonate, sodium citrate dihydrate, sodium hydroxide, sodium lactate and triethanolamine or a combination thereof.

6. The fludrocortisone oral solution as claimed in claim 1; wherein the flavoring agent is selected from the group comprising of anchovy, apple, banana, bubble Gum, butterscotch, marshmallow, vanilla, cherry, grape, peanut butter, peppermint, pina colada, raspberry, strawberry, tutti fruitti, vanilla butternut and venison or a combination thereof.

7. A method for treating the primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome, comprising administering to a patient in need thereof the fludrocortisone oral solution of claim 1.

, Description:TECHNICAL FIELD OF THE INVENTION
The invention in general relates to pharmaceutical dosage forms containing corticosteroid. Particularly, the invention relates to oral pharmaceutical composition comprising corticosteroid and method of administration of the said oral pharmaceutical composition.

BACKGROUND ART
Fludrocortisone is a synthetic adrenocortical steroid possessing very potent mineralocorticoid properties and high glucocorticoid activity. Fludrocortisone is indicated as a partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome. Fludrocortisone acetate tablets 0.1mg is approved by the US FDA and marketed as Florinef.
Current treatment with fludrocortisone for primary and secondary adrenocortical insufficiency in neonates and infants is unsatisfactory because the current approved adult dosage formulation of Florinef is not licensed for use in children. The approved dosage form of fludrocortisone (i.e. tablet) is difficult to administer to neonates and infants. As there is no approved fludrocortisone formulation for children under 6 years of age, fludrocortisone is often compounded by pharmacists using the Florinef tablets. The compounded fludrocortisone formulation does not provide appropriate unit dose and may give rise to inconsistencies in dose because the content uniformity of the administered dose cannot be verified.
Thus, there exists a long felt need for fludrocortisone formulations for pediatric and geriatric patient groups that provide appropriate unit dose that can be administered with ease.

SUMMARY OF THE INVENTION
Herein disclosed is a multi-dose fludrocortisone oral solution comprising of pharmaceutically effective amount of fludrocortisone or a pharmaceutically acceptable salt thereof, at least one vehicle, at least one preservative, at least one antioxidant, at least one buffering agent and at least one flavoring agent; wherein the pH of the oral solution is 3-9 and the concentration of the oral solution is about 0.05 to 0.3 mg/ml.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one vehicle selected from the group comprising of butylene glycol, polyethylene glycol, propylene glycol, glycerin monostearate, sorbitol, ethanol and propylene glycol or a combination thereof. The multi-dose fludrocortisone oral solution as disclosed herein may comprise a single vehicle or a combination one or more vehicles selected from the above listed vehicles.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one selected from the group comprising of benzalkonium chloride, benzoic acid, benzyl alcohol, boric acid, bronopol, butylated hydroxyanisole, butylene glycol, butylparaben, calcium acetate, cationic, and bentonite, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, dimethyl ether, ethylparaben, hexetidine, imidurea, inactivation by magnesium trisilicate, isopropyl alcohol, lactic acid, methylparaben, monothioglycerol, benzalkonium chloride, benzoic acid, benzyl alcohol, boric acid, bronopol, butylated hydroxyanisole, butylene glycol, butylparaben, calcium acetate, cationic, and bentonite, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, dimethyl ether, ethylparaben, hexetidine, imidurea, inactivation by magnesium trisilicate, isopropyl alcohol, lactic acid, methylparaben and monothioglycerol or a combination thereof. The multi-dose fludrocortisone oral solution as disclosed herein may comprise more than one preservative. The preservative may be a combination of two or more of the above listed preservatives.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one antioxidant selected from the group comprising of Propyl & octyl esters of gallic acid, tocopherols or vitamin E, sodium sulfite, ascorbic acid (vit. C), alpha tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, carbon dioxide, chelating agents, citric acid monohydrate, erythorbic acid, ethyl oleate, fumaric acid, malic acid, methionine, monothioglycerol, phosphoric acid, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium sulfite, sodium thiosulfate and sulfur dioxide or a combination thereof. The multi-dose fludrocortisone oral solution as disclosed herein may comprise a single antioxidant or a combination of two or more antioxidants.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one buffering agent selected from the group comprising of adipic acid, tartaric acid, boric acid, citric acid monohydrate, HCl, maleic acid, adipic acid, ammonia solution, boric acid, calcium carbonate, calcium hydroxide, calcium lactate, calcium phosphate, tribasic, dibasic sodium phosphate, diethanolamine, methionine, monobasic sodium phosphate, monoethanolamine, monosodium glutamate, phosphoric acid, potassium citrate, sodium acetate, sodium bicarbonate, sodium borate, sodium carbonate, sodium citrate dihydrate, sodium hydroxide, sodium lactate and triethanolamine or a combination thereof. The multi-dose fludrocortisone oral solution as disclosed herein may comprise a single buffering agent or may be a combination of two or more of the above said buffering agents.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one flavoring agent selected from the group comprising of anchovy, apple, banana, bubble gum, butterscotch, marshmallow, vanilla, cherry, grape, peanut butter, peppermint, pina colada, raspberry, strawberry, tutti fruitti, vanilla butternut and venison or a combination thereof. The multi-dose fludrocortisone oral solution as disclosed herein may comprise more than one flavoring agent. The flavoring agent may be single or a combination of two or more of the above said flavoring agents.
Further, the invention discloses a method of administering fludrocortisone for primary and secondary adrenocortical insufficiency, specifically in neonates and infants. The said method comprises of administering appropriate unit dose of fludrocortisone oral solution to the neonates and infants for treatment of primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome.

DETAILED DESCRIPTION OF THE INVENTION
Disclosed herein is fludrocortisone oral solution formulation for administration in neonates and infants for the treatment of primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome. The fludrocortisone oral solution formulation according to this invention provides for better treatment compliance in neonates and infants due to ease of administration and improved systemic availability.

The multi-dose fludrocortisone oral solution comprises of fludrocortisone or a pharmaceutically acceptable salt thereof, at least one vehicle, at least one preservative, at least one antioxidant, at least one buffering agent and at least one flavoring agent. The pH of the fludrocortisone oral solution as disclosed herein is 3-9 and the concentration of the fludrocortisone oral solution is about 0.05 to 0.2 mg/ml. The fludrocortisone oral solution is provided in amber colored, multi-dose bottle with dropper for easy administration to treat primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenogenital syndrome. The multi dose fludrocortisone oral solution comprises of about 0.01 mg to 0.5 mg of fludrocortisone or its pharmaceutically acceptable salts, preferably 0.05 mg to 0.3 mg of fludrocortisone acetate.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one vehicle selected from the group comprising of butylene glycol, polyethylene glycol, propylene glycol, glycerin monostearate, sorbitol, ethanol and propylene glycol or a combination thereof. The multi-dose fludrocortisone oral solution according to the invention comprises of about 40% to 90% w/w of vehicle. According to one embodiment the fludrocortisone oral solution comprises of 40% to 70% w/w of vehicle. According to another embodiment the fludrocortisone oral solution comprises of 70% to 90% w/w of vehicle. According to one embodiment the multi-dose fludrocortisone oral solution as disclosed herein comprises of more than one vehicle or a combination of two or more vehicles.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one preservative selected from the group comprising of benzalkonium chloride, benzoic acid, benzyl alcohol, boric acid, bronopol, butylated hydroxyanisole, butylene glycol, butylparaben, calcium acetate, cationic, and bentonite, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, dimethyl ether, ethylparaben, hexetidine, imidurea, inactivation by magnesium trisilicate, isopropyl alcohol, lactic acid, methylparaben, monothioglycerol, benzalkonium chloride, benzoic acid, benzyl alcohol, boric acid, bronopol, butylated hydroxyanisole, butylene glycol, butylparaben, calcium acetate, cationic, and bentonite, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, dimethyl ether, ethylparaben, hexetidine, imidurea, inactivation by magnesium trisilicate, isopropyl alcohol, lactic acid, methylparaben and monothioglycerol or a combination thereof. The multi-dose fludrocortisone oral solution according to the invention comprises of about 0.01% to 1% w/w of preservative. According to one embodiment the fludrocortisone oral solution comprises of 0.03% to 0.1% w/w of preservative. The multi-dose fludrocortisone oral solution as disclosed herein comprises of a single preservative or a combination of two or more preservatives.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one antioxidant selected from the group comprising of Propyl & octyl esters of gallic acid, tocopherols or vitamin E, sodium sulfite, ascorbic acid (vit. C), alpha tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, carbon dioxide, chelating agents, citric acid monohydrate, erythorbic acid, ethyl oleate, fumaric acid, malic acid, methionine, monothioglycerol, phosphoric acid, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, Sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium sulfite, sodium thiosulfate and sulfur dioxide or a combination thereof. The multi-dose fludrocortisone oral solution according to the invention comprises of about 0.1% to 2% w/w of antioxidant. According to one embodiment the fludrocortisone oral solution comprises of about 0.3% to 1% w/w of antioxidant. The multi-dose fludrocortisone oral solution as disclosed herein comprises of a single antioxidant or a combination of two or more antioxidants.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one buffering agent selected from the group comprising of adipic acid, tartaric acid, boric acid, citric acid monohydrate, HCl, maleic acid, adipic acid, ammonia solution, boric acid, calcium carbonate, calcium hydroxide, calcium lactate, calcium phosphate, tribasic, dibasic sodium phosphate, diethanolamine, methionine, monobasic sodium phosphate, monoethanolamine, monosodium glutamate, phosphoric acid, potassium citrate, sodium acetate, sodium bicarbonate, sodium borate, sodium carbonate, sodium citrate dihydrate, sodium hydroxide, sodium lactate and triethanolamine or a combination thereof. The multi-dose fludrocortisone oral solution according to the invention comprises of about 0.01% to 1% w/w of buffering agent. The multi-dose fludrocortisone oral solution as disclosed herein comprises of one buffering agent or a combination of two or more buffering agents.
The multi-dose fludrocortisone oral solution according to the invention comprises of at least one flavoring agent selected from the group comprising of anchovy, apple, banana, bubble Gum, butterscotch, marshmallow, vanilla, cherry, grape, peanut butter, peppermint, pina colada, raspberry, strawberry, tutti fruitti, vanilla butternut and venison or a combination thereof. The multi-dose fludrocortisone oral solution as disclosed herein may comprise more than one flavoring agent. The flavoring agent may be a combination of two or more of the above said flavoring agents.
According to one embodiment the multidose fludrocortisone oral solution is prepared by adding vehicle to the required quantity of water and stirring well to prepare the glycerin phase. To the glycerin phase a preservative is added under stirring and continuing the stirring till a clear solution is obtained. After dissolving the preservative, buffering agent is added under stirring and continuing the stirring for 10 – 15 minutes or till a clear solution is obtained (Phase – I). Dissolving the API in vehicle under stirring and continuing stirring till a clear solution is obtained. After dissolving the API, antioxidant is added and stirring is continued till a clear solution is obtained (Phase – II). Then Phase – I is added to Phase – II and stirred well. Finally, flavor is added and volume is made up to the required quantity with purified water. In one embodiment the vehicle is a combination of two vehicles.

Fludrocortisone Oral solution compositions
Table 1
S No API/Excipient(s) mg/ml % w/v
1 Fludrocortisone 0.05 0.005
2 Glycerin 150.00 15
3 PEG 600 400.00 40
4 Sodium benzoate 0.50 0.05
5 Propylene glycol 250.00 25
6 Citric acid 0.37 0.037
7 Purified water q. s.
8 pH 6 - 8

Table 2
S No API/Excipient(s) mg/ml % w/v
1 Fludrocortisone 0.05 0.005
2 Glycerin 250.00 25
3 PEG 400 400.00 40
4 Sodium benzoate 0.50 0.05
5 BHA 0.15 0.015
6 Disodium hydrogen phosphate dihydrate 0.5 0.05
7 Purified water q. s.
8 pH 3 - 5

Table 3
S No API/Excipient(s) mg/ml % w/v
1 Fludrocortisone 0.05 0.005
2 Glycerin 50.00 5
3 PEG 600 400.00 40
4 Sodium benzoate 0.50 0.05
5 BHA 0.1 0.01
6 Citric acid 0.37 0.037
7 Volume make up with propylene glycol Upto 1 ml
8 pH 6 - 8

Table 4
S No API/Excipient(s) mg/ml % w/v
1 Fludrocortisone 0.05 0.005
2 Glycerin 150.00 15
3 PEG 400 400.00 40
4 Sodium benzoate 0.50 0.05
5 Disodium hydrogen phosphate dihydrate 0.5 0.05
6 Volume make up with glycerol Upto I ml
7 pH 3 - 5

Table 5
S No API/Excipient(s) mg/ml % w/v
1 Fludrocortisone 0.05 0.005
2 Glycerin 150.00 15
3 PEG 600 400.00 40
4 Sodium benzoate 0.50 0.05
5 BHA 0.1 0.01
6 Citric acid 0.37 0.037
7 Grape flavor 1 0.1
8 Volume make up with glycerine Upto 1 ml
9 pH 3 - 6

Table 6
S No API/Excipient(s) mg/ml % w/v
1 Fludrocortisone 0.05 0.005
2 Glycerin 250.00 25
3 PEG 400 400.00 40
4 Sodium benzoate 0.50 0.05
5 BHA 0.05 0.005
6 Disodium hydrogen phosphate dihydrate 0.5 0.05
7 Honey flavor 1 0.1
8 Volume make up with PEG400 Upto 1 ml
9 pH 6 -9

Manufacturing procedures for Fludrocortisone oral solution
Example 1
Add vehicle to the required quantity of water and stir well to prepare the glycerin phase. To the glycerin phase add preservative under stirring and continue the stirring till a clear solution is obtained. After dissolving the preservative, add buffering agent under stirring and continue the stirring for 10 – 15 minutes to get a get clear solution (Phase – I). Dissolve the API in vehicle under stirring and continue stirring for 5 – 15 minutes to obtain a clear solution. After dissolving the API, add antioxidant to it and continue the stirring till a clear solution is obtained (Phase – II). Add Phase – I to Phase – II and stir well. Finally add the flavor and make up the volume to the required volume with purified water.

Example 2
Glycerin is added to the required quantity of water and stirred well to prepare the glycerin phase. To the glycerin phase, sodium benzoate is added under stirring and the stirring is continued till a clear solution is obtained. After dissolving the sodium benzoate in the glycerin phase, citric acid is added under stirring and the stirring is continued for 10 – 15 minutes to get a clear solution (Phase – I). Separately fludrocortisone is dissolved in PEG600 under stirring and continued the stirring for 5 – 15 minutes to obtain a clear solution (Phase – II). Then Phase – I is added to Phase – II and stirred well. Finally, flavor is added and volume is made up to the required volume with purified water.

Example 3
First Glycerin phase is prepared by adding glycerin to the required quantity of water and stirred well. To the glycerin phase, sodium benzoate is added under stirring and the stirring is continued till a clear solution is obtained. After dissolving the sodium benzoate in the glycerin phase, citric acid is added under stirring and the stirring is continued for 10 – 15 minutes to get a clear solution (Phase – I). Separately fludrocortisone is dissolved in PEG400 under stirring and continued the stirring for 5 – 15 minutes to obtain a clear solution. After dissolving fludrocortisone in PEG600, BHA is added to it and continued the stirring till a clear solution is obtained (Phase – II). Then Phase – I is added to Phase – II and stirred well. Finally, flavor is added and volume is made up to the required volume with purified water.

Example 4
Glycerin is added to the required quantity of water and stirred well to prepare the glycerin phase. To the glycerin phase, sodium benzoate is added under stirring and the stirring is continued till a clear solution is obtained. After dissolving the sodium benzoate in the glycerin phase, citric acid is added under stirring and the stirring is continued till a clear solution is obtained (Phase – I). Separately fludrocortisone is dissolved in PEG600 and propylene glycol under stirring and continued the stirring till a clear solution is obtained (Phase – II). Then Phase – I is added to Phase – II and stirred well. Finally, flavor is added and volume is made up to the required volume with purified water.

Example 5
Glycerin is added to the required quantity of water and stirred well to prepare the glycerin phase. To the glycerin phase, sodium benzoate is added under stirring and the stirring is continued till a clear solution is obtained. After dissolving the sodium benzoate in the glycerin phase, citric acid is added under stirring and the stirring is continued for 10 – 15 minutes to get a clear solution (Phase – I). Separately fludrocortisone is dissolved in PEG600 under stirring and continued the stirring for 5 – 15 minutes to obtain a clear solution (Phase – II). Then Phase – I is added to Phase – II and stirred well. Finally, flavor is added and volume is made up to the required volume with propylene glycol.

Example 6
First Glycerin phase is prepared by adding glycerin to the required quantity of water and stirred well. To the glycerin phase, sodium benzoate is added under stirring and the stirring is continued till a clear solution is obtained. After dissolving the sodium benzoate in the glycerin phase, citric acid is added under stirring and the stirring is continued till a clear solution is obtained (Phase – I). Separately fludrocortisone is dissolved in PEG400 under stirring and continued the stirring to obtain a clear solution (Phase – II). Then Phase – I is added to Phase – II and stirred well. Finally, flavor is added and volume is made up to the required volume with glycerol.

Example 7
Glycerin is added to the required quantity of water and stirred well to prepare the glycerin phase. To the glycerin phase, sodium benzoate is added under stirring and the stirring is continued till a clear solution is obtained. After dissolving the sodium benzoate in the glycerin phase, citric acid is added under stirring and the stirring is continued till a clear solution is obtained (Phase – I). Separately fludrocortisone is dissolved in PEG600 and propylene glycol under stirring and continued the stirring till a clear solution is obtained (Phase – II). Then Phase – I is added to Phase – II and stirred well. Finally, flavor is added and volume is made up to the required volume with propylene glycol.

Example 8
Sodium benzoate is dissolved in required quantity of glycerin under stirring with nitrogen purging, continuing the stirring till a clear solution is obtained. To this solution is added citric acid and stirred for about 10 – 15 minutes or till a clear solution is obtained. Nitrogen purging is maintained during the dissolving of citric acid. Fludrocortisone is dissolved in PEG600 and propylene glycol under stirring and continued the stirring for 5 to 15 minutes or till a clear solution is obtained (Phase – II). Then Phase – I is added to Phase – II and stirred well under nitrogen purging. Finally, flavor is added and volume is made up to the required quantity with glycerin and the solution is kept under nitrogen purging for about 30 to 60 minutes before filling the solution into container.

Example 9
Sodium benzoate is dissolved in required quantity of glycerin under stirring with nitrogen purging, continuing the stirring till a clear solution is obtained. To this solution is added citric acid and/or disodium hydrogen phosphate hydrate and stirred for about 10 – 15 minutes or till a clear solution is obtained. Nitrogen purging is maintained during the dissolving of citric acid. Fludrocortisone is dissolved in PEG400 under stirring and continued the stirring for 5 to 15 minutes or till a clear solution is obtained (Phase – II). Then Phase – I is added to Phase – II and stirred well under nitrogen purging. Finally, flavor is added and volume is made up to the required quantity with PEG400 and the solution is kept under nitrogen purging for about 30 to 60 minutes before filling the solution into container.

Example 10
Sodium benzoate is dissolved in required quantity of glycerin under stirring with nitrogen purging, continuing the stirring till a clear solution is obtained. To this solution is added citric acid and stirred for about 10 – 15 minutes or till a clear solution is obtained. Nitrogen purging is maintained during the dissolving of citric acid. Fludrocortisone is dissolved in PEG600 under stirring and continued the stirring for 5 to 15 minutes or till a clear solution is obtained (Phase – II). Then Phase – I is added to Phase – II and stirred well under nitrogen purging. Finally, flavor is added and volume is made up to the required quantity with glycerin and the solution is kept under nitrogen purging for about 30 to 60 minutes before filling the solution into container.

According to one embodiment the invention provides a method for treating the primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome comprising administering to a patient in need thereof a fludrocortisone oral solution comprising of fludrocortisone or a pharmaceutically acceptable salt thereof, at least one vehicle, at least one preservative, at least one antioxidant, at least one buffering agent and at least one flavoring agent.