Claims for Patent: 9,649,280

Summary for Patent: 9,649,280

Title:	Composition comprising hydrocortisone
Abstract:	The disclosure relates to pharmaceutical compositions useful in the treatment of adrenal insufficiency in paediatric or elderly subjects.
Inventor(s):	Huatan; Hiep (Maidstone, GB), Ross; Richard (Sheffield, GB), Whitaker; Martin (Nottingham, GB), Poellinger; Norbert (Mullheim, DE), Grave; Annette (Lorrach, DE)
Assignee:	Diurnal Limited (Cardiff, GB)
Application Number:	14/888,648
Patent Claims:	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 .mu.m. 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 .mu.m 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 .mu.m 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.