Immediate-release tablets containing combimetinib and methods of making and using the same

A pharmaceutical dosage unit tablet core, the tablet core comprising:

• (1) about 5 wt. % or more of a particulate pharmaceutical active drug;
• (2) a lubricant at a content based on the pharmaceutical dosage unit tablet core weight of from about 0.5 wt. % to about 5 wt. %, from about 0.5 wt. % to about 3 wt. %, from about 1 wt. % to about 3 wt. %, from about 1 wt. % to about 2.5 wt. %, or from about 1.5 wt. % to about 2 wt. %;
• (3) a disintegrant at a content based on the pharmaceutical dosage unit tablet core weight of from about 2 wt. % to about 7 wt. %, from about 2 wt. % to about 6 wt. %, from about 2 wt. % to about 5 wt. %, from about 3 wt. % to about 6 wt. %, or from about 3 wt. % to about 5 wt. %;
• (4) a filler at a content based on the pharmaceutical dosage unit tablet core weight of from about 60 wt. % to about 78 wt. %, from about 65 wt. % to about 78 wt. %, from about 65 wt. % to about 77 wt. %, from about 70 wt. % to about 77 wt. %, or from about 71 wt. % to about 75 wt. %;
• and
• (5) optionally, up to 10 wt. % of a binder,
• wherein the particulate pharmaceutical active drug is cobimetinib hemifumarate polymorph Form A.

A pharmaceutical dosage unit tablet core, the tablet core comprising:

• (1) 18.5 wt. % cobimetinib hemifumarate polymorph Form A;
• (2) 45.6 wt. % microcrystalline cellulose;
• (3) 30.4 wt. % lactose monohydrate;
• (4) 4 wt. % croscarmellose sodium;
• and
• (5) 1.5 wt. % magnesium stearate.

A coated pharmaceutical dosage unit tablet core, the coated tablet comprising:

• (1) 17.79 wt. % cobimetinib hemifumarate polymorph Form A;
• (2) 43.85 wt. % microcrystalline cellulose;
• (3) 29.23 wt. % lactose monohydrate;
• (4) 3.84 wt. % croscarmellose sodium;
• (5) 1.45 wt. % magnesium stearate;
• and
• (6) 3.85 wt. % film coating.

A process for preparing a coated pharmaceutical dosage unit tablet, the process comprising the following steps:

• (1) combining a particulate filler component, a first particulate disintegrant component and cobimetinib hemifumarate polymorph Form A in a blender and admixing said components to form a primary pre-blend;
• (2) combining a particulate first lubricant component with the primary pre-blend in a blender and admixing said first lubricant component and primary pre-blend to form a finished preblend;
• (3) dry granulating the finished pre-blend to form granules;
• (4) combining the granules and a second particulate disintegrant component in a blender and admixing said granules and disintegrant component to form a primary final blend;
• (5) combining a second particulate lubricant component and the primary final blend in a blender and admixing said second lubricant component and primary final blend to form a finished final blend;
• (6) tableting the finished final blend to form tablet cores;
• and
• (7) coating the tablet cores.