Composition comprising hydrocortisone

1. A pharmaceutical composition adapted for oral administration comprising:

a micro-particulate carrier;

a drug layer comprising an effective amount of hydrocortisone and a binding agent;

a taste masking polymer layer comprising 0.14-0.16% w/w hydroxypropylmethylcellulose and 0.58-0.62% w/w ethylcellulose; and

a sealing polymer layer that separates the drug layer and the taste masking polymer layer, wherein the sealing polymer layer consists of 14-16% w/w hydroxypropylmethylcellulose and 1-2% w/w magnesium stearate;

wherein the drug layer is in contact with the micro-particulate carrier and with the sealing polymer layer.

2. The composition according to claim 1 wherein said effective amount of hydrocortisone is between about 0.25 mg w/w and 30 mg w/w hydrocortisone per unit dose.

3. The composition according to claim 1 , wherein said carrier comprises microcrystalline cellulose particles with a diameter of between 350-500 μm.

4. The composition of claim 1 , wherein the binding agent is between 0.60-0.70% w/w of the composition.

5. The composition according to claim 1 , wherein the binding agent is hydroxypropylmethylcellulose.

6. The composition according to claim 1 , wherein the sealing layer is 15-25% w/w of the composition.

7. The composition according to claim 1 , wherein said sealing layer consists of about 15% w/w hydroxypropylmethylcellulose and about 1.5% w/w magnesium stearate.

8. The composition according to claim 1 , wherein the taste masking polymer layer is between 0.5%-1.5% w/w of the composition.

9. The composition according to claim 1 , wherein the taste masking polymer layer comprises hydroxypropylmethylcellulose is at about 0.15% w/w of the composition and ethylcellulose at about 0.60% w/w of the composition.

10. The composition according to claim 1 , wherein the weight ratio of ethylcellulose to hydroxypropylmethylcellulose is 4:1 in the taste masking layer.

11. The pharmaceutical composition of claim 1 , wherein:

i) the micro-particulate carrier comprises 80-81% w/w micro-particulates, wherein said micro-particulates are 350-500 μm in diameter;

ii) the drug layer comprises 0.64-0.66% w/w hydrocortisone and 0.64-0.66% w/w hydroxypropylmethylcellulose;

iii) the sealing layer consists of 14-16% w/w hydroxypropylmethylcellulose and 1.0-2.0% w/w magnesium stearate; and

iv) the taste masking layer further comprises 0.20-0.25% w/w magnesium stearate.

12. The pharmaceutical composition according to claim 11 wherein:

i) the micro-particulate carrier consists of 81% w/w micro-particulates;

ii) the drug layer consists of 0.66% w/w hydrocortisone and 0.66% w/w hydroxypropylmethylcellulose;

iii) the sealing layer consists of 15% w/w hydroxypropylmethylcellulose and 1.5% magnesium stearate; and

iv) the taste masking layer consists of 0.15% w/w hydroxypropylmethylcellulose, 0.61% w/w ethylcellulose, and 0.23% w/w magnesium stearate.

13. The composition according to claim 1 , wherein the composition is adapted for immediate release of hydrocortisone.

14. The composition according to claim 13 wherein hydrocortisone is not released before about 5 minutes in aqueous conditions in the mouth.

15. The composition according to claim 13 wherein hydrocortisone is released after swallowing.

16. The composition according to claim 15 , wherein:

at least 70% of hydrocortisone contained in said composition is released 15 minutes after swallowing, or

at least 90% of hydrocortisone contained in said composition is released 60 minutes after swallowing.

17. A method of treating adrenal insufficiency in a subject, comprising:

administering an effective amount of the composition of claim 1 to the subject, thereby treating the adrenal insufficiency.

18. The method according to claim 17 , wherein the adrenal insufficiency is caused by primary or secondary or tertiary adrenal failure, congenital adrenal hyperplasia, late-onset congenital adrenal hyperplasia, polycystic ovarian failure, or glucocorticoid-remediable aldosteronism (GRA).

19. The method of claim 17 , wherein the subject is a paediatric subject, and wherein the composition is administered at least once a day.

20. The method according to claim 19 , wherein said composition is administered three to four times a day at approximately six hour intervals.

21. A pharmaceutical composition adapted for oral administration, comprising:

i) a carrier comprising 80-81% w/w micro-particulates, wherein said micro-particulates are 350-500 μm in diameter;

ii) a drug layer comprising 0.64-0.66% w/w hydrocortisone and 0.64-0.66% w/w hydroxypropylmethylcellulose, in contact with the carrier;

iii) a sealing layer consisting of 14-16% w/w hydroxypropylmethylcellulose and 1.0-2.0% w/w magnesium stearate, in contact with the drug layer; and

iv) a taste masking layer comprising 0.14-0.16% w/w hydroxypropylmethylcellulose, 0.58-0.62% w/w ethylcellulose, and 0.20-0.25% w/w magnesium stearate, in contact with the sealing layer.

22. A pharmaceutical composition adapted for oral administration, comprising:

i) a carrier consisting of 81% w/w micro-particulates;

ii) a drug layer consisting of 0.66% w/w hydrocortisone and 0.66% w/w hydroxypropylmethylcellulose, in contact with the carrier;

iii) a sealing layer consisting of 15% w/w hydroxypropylmethylcellulose and 1.5% magnesium stearate, in contact with the drug layer; and

iv) a taste masking layer consisting of 0.15% w/w hydroxypropylmethylcellulose, 0.61% w/w ethylcellulose, and 0.23% w/w magnesium stearate, in contact with the sealing layer.

23. A pharmaceutical composition adapted for oral administration comprising:

a micro-particulate carrier;

a drug layer comprising an effective amount of hydrocortisone and a binding agent;

a taste masking layer comprising 0.14-0.16% w/w hydroxypropylmethylcellulose and 0.58-0.62% w/w ethylcellulose; and

a sealing polymer layer that separates the drug layer and the taste masking polymer layer wherein the sealing polymer layer consists of 15% w/w hydroxypropylmethylcellulose and 1.5% magnesium stearate;

wherein the drug layer is in contact with the micro-particulate carrier and with the sealing polymer layer.