Pharmaceutical compositions

1. A sustained release pharmaceutical composition consisting of (I) a matrix form comprising:

(a) 0.001-60% w/w of liothyronine or the sodium salt of liothyronine;

(b) 10-60% w/w of microcrystalline cellulose;

(c) 10-60% w/w of a diluent;

(d) 5-25% w/w of a glidant; and

(e) one or more of ethylcellulose having an ethoxyl substitution of from 47 to 51% and a viscosity (5% solution in 80/20 toluene/ethanol) of from 5 to 40 cps, stearic acid and a salt of stearic acid, in an amount such that the total weight of component (e) is from 10 to 60% w/w; and (II) an optional enteric coating, coating the matrix.

2. A composition as claimed in claim 1 obtained by a process comprising extrusion-spheronisation.

3. A composition as claimed in claim 1 in which component (e) of the matrix comprises from 20 to about 50% w/w of ethylcellulose, stearic acid or a salt of stearic acid or a combination thereof.

4. A composition as claimed in claim 1 , wherein component (e) is ethylcellulose only.

5. A composition as claimed in claim 1 , wherein the ethylcellulose has an ethoxyl substitution in the range 49.6 to 51.0% and a viscosity (5% solution in 80/20 toluene/ethanol) of 8 to 11 cps.

6. A composition as claimed in claim 1 , wherein the amount of stearic acid present in the matrix is 30% w/w or below.

7. A composition as claimed in claim 1 , wherein the amount of stearic acid in the matrix is from 10 to 25% w/w.

8. A composition as claimed in claim 1 , wherein the amount of stearic acid salts present in the matrix is 50% w/w or below.

9. A composition as claimed in claim 1 , wherein the amount of microcrystalline cellulose in the matrix is from 20 to 50% w/w.

10. A composition as claimed in claim 1 , wherein the glidant is talc.

11. A composition as claimed in claim 1 , wherein the amount of glidant in the matrix is from 10 to 20% w/w.

12. A composition as claimed in claim 1 , wherein the diluent is starch.

13. A composition as claimed in claim 1 , wherein the amount of diluent in the matrix is from 15 to 35% w/w.

14. A composition as claimed in claim 1 , wherein the amount of liothyronine or the sodium salt of liothyronine in the matrix is from 0.002 to 50% w/w.

15. A composition as claimed in claim 1 , which exhibits a release in an in vitro dissolution test of at least 50% of drug within a period of around 4 hours, and at least 70% within a period of around 6 hours.

16. A composition as claimed in claim 1 , which exhibits a release in an in vitro dissolution test of at least 50% of drug within a period of around 8 hours, and at least 70% within a period of around 12 hours.

17. A composition as claimed in claim 15 , in which the matrix comprises ethylcellulose, starch (as the diluent) and talc (as the glidant).

18. A composition as claimed in claim 17 , in which the matrix comprises 0.001 to 1% w/w of liothyronine or a salt thereof; 20 to 40% w/w of microcrystalline cellulose; 15 to 55% w/w of starch, 10 to 20% w/w of talc; and 15 to 25% w/w of ethylcellulose.

19. A composition as claimed in claim 16 , in which the matrix comprises stearic acid and/or a salt thereof, starch (as the diluent) and talc (as the glidant).

20. A composition as claimed in claim 19 , in which the matrix comprises 0.001 to 1% w/w of liothyronine or a salt thereof; 20 to 40% w/w of microcrystalline cellulose; 15 to 35% w/w of starch, 5 to 20% w/w of talc; 10 to 30% w/w of calcium stearate; and 5 to 15% w/w of stearic acid.

21. A composition as claimed in claim 1 , which is in the form of pellets.

22. A composition as claimed in claim 21 , wherein the pellet diameter is from 0.1 to 2 mm.

23. A composition as claimed in claim 21 , wherein the pellets are contained within hard capsules made from gelatin, hydroxypropylmethylcellulose, pullulan or starch.

24. A composition as claimed in claim 21 , wherein the pellets consist essentially of liothyronine or the sodium salt of liothyronine, microcrystalline cellulose, a diluent, a glidant and ethylcellulose.

25. A process for the preparation of a composition as defined in claim 1 , which comprises preparing a heavy granule or wet mass by mixing the ingredients with sufficient water to form a paste, passing the paste through an extruder, transferring the extrudate to a spheronizer, and then drying the particles so formed.

26. A method of providing sustained release of a drug into systemic circulation, which comprises administration of a composition as defined in claim 1 to a patient in need of such sustained release.

27. A method of treatment of congestive heart failure which comprises administration of a composition as defined in claim 1 to a patient in need of such treatment.