SOLID DOSAGE FORMS OF VALSARTAN, AMLODIPINE AND HYDROCHLOROTHIAZIDE AND METHOD OF MAKING THE SAME

1 . A solid dosage form comprising:

valsartan;

amlodipine;

hydrochlorothiazide; and

pharmaceutically acceptable additives suitable for the preparation of solid dosage forms of valsartan.

2 . The solid dosage form of claim 1 , wherein the amlodipine is provided in the form of amlodipine besylate.

3 . The solid dosage form of claim 1 , wherein the solid dosage form takes the form of a monolayer tablet.

4 . The solid dosage form of claim 1 , wherein the solid dosage form takes the form of a bilayer tablet.

5 . The solid dosage form of claim 4 , wherein the bilayer tablet has the valsartan and the hydrochlorothiazide in a first layer and the amlodipine in a second layer.

6 . The solid dosage form of claim 4 , wherein the bilayer tablet has the valsartan in a first layer and the amlodipine and the hydrochlorothiazide in a second layer.

7 . The solid dosage form of claim 1 , wherein the valsartan is employed in an amount ranging from about 80 mg to about 640 mg.

8 . The solid dosage form of claim 7 , wherein the valsartan is employed in an amount selected from 160 mg and 320 mg.

9 . The solid dosage form of claim 1 , wherein the amlodipine is employed in an amount ranging from about 2.5 mg to about 20 mg.

10 . The solid dosage form of claim 9 , wherein the amlodipine is employed in an amount selected from 5 mg and 10 mg.

11 . The solid dosage form of claim 1 , wherein the hydrochlorothiazide is employed in an amount ranging from about 6.25 mg to about 50 mg.

12 . The solid dosage form of claim 11 , wherein the hydrochlorothiazide is employed in an amount selected from 12.5 mg and 25 mg.

13 . The solid dosage form of claim 1 , wherein the pharmaceutically acceptable additives are selected from the group consisting of diluents, disintegrants, glidants, lubricants, binders, colorants and combinations thereof.

14 . A method of making a solid dosage form comprising the steps of:

(a) blending valsartan, amlodipine, hydrochlorothiazide and pharmaceutically acceptable additives to form a blended material;

(b) sieving the blended material to form a sieved material;

(c) blending the sieved material to form a blended/sieved material;

(d) compacting the blended/sieved material to form a compacted material;

(e) milling the compacted material to form a milled material;

(f) blending the milled material to form blended/milled material; and

(g) compressing the blended/milled material to form a monolayer solid dosage form.

15 . The method of claim 14 further comprising the step of:

(h) film coating the monolayer solid dosage form.

16 . A method of making a solid dosage form comprising the steps of:

(a) granulating valsartan, pharmaceutically acceptable additives and optionally hydrochlorothiazide to form a valsartan granulation;

(b) blending amlodipine, pharmaceutically acceptable additives and optionally hydrochlorothiazide to form an amlodipine blend; and

(c) compressing the valsartan granulation and the amlodipine blend together to form a bilayer solid dosage form,

wherein hydrochlorothiazide is present in the valsartan granulation and/or the amlodipine blend.

17 . The method of claim 16 , wherein step (a) comprises the steps of:

(a1) blending valsartan, pharmaceutically acceptable additives and hydrochlorothiazide to form a blended material;

(a2) sieving the blended material to form a sieved material;

(a3) blending the sieved material to form a blended/sieved material;

(a4) compacting the blended/sieved material to form a compacted material;

(a5) milling the compacted material to form a milled material; and

(a6) blending the milled material to form the valsartan granulation.

18 . The method of claim 16 , wherein step (a) comprises the steps of:

(a1) blending valsartan and pharmaceutically acceptable additives to form a blended material;

(a2) sieving the blended material to form a sieved material;

(a3) blending the sieved material to form a blended/sieved material;

(a4) compacting the blended/sieved material to form a compacted material;

(a5) milling the compacted material to form a milled material; and

(a6) blending the milled material and hydrochlorothiazide to form the valsartan granulation.

19 . The method of claim 16 , wherein step (b) comprises a granulation process comprising the steps of:

(b1) blending amlodipine, pharmaceutically acceptable additives and hydrochlorothiazide to form a blended material;

(b2) sieving the blended material to form a sieved material;

(b3) blending the sieved material to form a blended/sieved material;

(b4) compacting the blended/sieved material to form a compacted material;

(b5) milling the compacted material to form a milled material; and

(b6) blending the milled material to form an amlodipine granulation.

20 . The method of claim 16 , wherein step (b) comprises a granulation process comprising the steps of:

(b1) blending amlodipine and pharmaceutically acceptable additives to form a blended material;

(b2) sieving the blended material to form a sieved material;

(b3) blending the sieved material to form a blended/sieved material;

(b4) compacting the blended/sieved material to form a compacted material;

(b5) milling the compacted material to form a milled material; and

(b6) blending the milled material and hydrochlorothiazide to form an amlodipine granulation.

21 . The method of claim 16 further comprising the step of:

(d) film coating the bilayer solid dosage form.

22 . A method of making a solid dosage form comprising the steps of:

(a) granulating valsartan, pharmaceutically acceptable additives and amlodipine to form a valsartan granulation;

(b) blending hydrochlorothiazide, pharmaceutically acceptable additives to form a hydrochlorothiazide blend; and

(c) compressing the valsartan granulation and the hydrochlorothiazide blend together to form a bilayer solid dosage form.

23 . The method of claim 22 , wherein step (a) comprises the steps of:

(a1) blending valsartan, pharmaceutically acceptable additives and amlodipine to form a blended material;

(a2) sieving the blended material to form a sieved material;

(a3) blending the sieved material to form a blended/sieved material;

(a4) compacting the blended/sieved material to form a compacted material;

(a5) milling the compacted material to form a milled material; and

(a6) blending the milled material to form the valsartan granulation.

24 . The method of claim 22 , wherein step (a) comprises the steps of:

(a1) blending valsartan and pharmaceutically acceptable additives to form a blended material;

(a2) sieving the blended material to form a sieved material;

(a3) blending the sieved material to form a blended/sieved material;

(a4) compacting the blended/sieved material to form a compacted material;

(a5) milling the compacted material to form a milled material; and

(a6) blending the milled material and amlodipine to form the valsartan granulation.

25 . The method of claim 22 , wherein step (b) comprises a granulation process comprising the steps of:

(b1) blending hydrochlorothiazide and pharmaceutically acceptable additives to form a blended material;

(b2) sieving the blended material to form a sieved material;

(b3) blending the sieved material to form a blended/sieved material;

(b4) compacting the blended/sieved material to form a compacted material;

(b5) milling the compacted material to form a milled material; and

(b6) blending the milled material to form a hydrochlorothiazide granulation.

26 . The method of claim 22 further comprising the step of:

(d) film coating the bilayer solid dosage form.

27 . A method of treating hypertension, congestive heart failure, angina, myocardial infarction, arteriosclerosis, diabetic nephropathy, diabetic cardiac myopathy, renal insufficiency, peripheral vascular disease, stroke, left ventricular hypertrophy, cognitive dysfunction, headache, or chronic heart failure, wherein the method comprises administering a solid dosage form as defined in claim 1 to a subject in need of such treatment.

28 . The method of treating according to claim 27 , wherein the solid dosage form is orally administered to the subject.