Wet granulation using a water sequestering agent

1. A method for formulating (6-(5-fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino)-2,2-dimethyl-3-oxo-2H-pyrido[3,2-b ][1,4]oxazin-4(3H)-yl)methyl phosphate disodium salt into a formulation for tablet compression, which method comprises:

a) blending (6-(5-fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino) -2,2-dimethyl-3-oxo-2H-pyrido[3,2-b][1,4]oxazin-4(3H)-yl)methyl phosphate disodium salt with starch and optionally at least one of a filler, a lubricant, a suspending/dispersing agent, a binding agent and a disintegrant, at an impellor speed sufficient to form a homogenous powder mixture having a bulk density after drying of about 6 kp to about 30 kp;

b) spraying into the homogenous powder mixture between about 15% and about 40% by weight of water with respect to the total weight of the powder mixture plus water and mixing to form wet granules; and

c) drying the wet granules until a loss on drying of between about 5% and about 11% is achieved, to provide dried granules.

2. The method of claim 1 , wherein the dried granules are sized between about 25 μm to about 900 μm in diameter.

3. The method of claim 1 which further comprises milling the dried granules, to provide milled granules.

4. The method of claim 3 , wherein the dried granules are milled so that about 90 weight percent of the milled granules have a particle size between about 25 to about 900 μm in diameter.

5. The method of claim 4 , further comprising mixing the milled granules with a lubricant until homogenous, and then tabletting the resulting formulation.

6. A wet granulating process, comprising:

a) blending a composition comprising (6-(5-fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino)-2,2-dimethyl-3-oxo-2H-pyrido[3,2-b ][1,4]oxazin-4(3H)-yl)methyl phosphate disodium salt and a sufficient amount of a water sequestering agent for inhibiting the decomposition of (6-(5-fluoro-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-ylamino)-2,2-dimethyl-3-oxo-2H-pyrido [3,2-b][1,4]oxazin-4(3H)-yl)methyl phosphate disodium salt to form a blended mixture;

b) granulating the blended mixture while adding water to form wet granules;

c) drying the wet granules at 65 ° C. until a loss on drying of between about 5% and 11% is achieved to provide dried granules; and

d) blending a lubricant into the dried granules to provide blended granules.

7. The method of claim 6 , further comprising:

compressing the blended granules to form tablets.