Pharmaceutical formulations of a pan-RAF kinase inhibitor and processes for their preparation
The invention relates to a pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof for the treatment of cancer and a process for its preparation. The invention also relates to administering the pharmaceutical composition to a patient according to an intermittent dosing regimen.
1. A pharmaceutical composition comprising:
(1) 10% to 50% w/w of a solid dispersion extrudate comprising:
(a) about 40% w/w of (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof, and
(b) about 60% w/w of copovidone; and
(2) 90% to 50% w/w of one or more pharmaceutically acceptable excipients,
wherein the solid dispersion extrudate comprises <3% w/w of (S)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide.
2. The pharmaceutical composition of claim 1 , which comprises croscarmellose sodium.
3. The pharmaceutical composition of claim 1 , which comprises colloidal silicon dioxide.
4. The pharmaceutical composition of claim 1 , which comprises magnesium stearate.
5. The pharmaceutical composition of claim 1 , which comprises microcrystalline cellulose.
6. A process for preparing a pharmaceutical composition of claim 1 , which comprises:
(i) extruding a mixture of (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide, or a pharmaceutically acceptable salt thereof, and copovidone to form a solid dispersion extrudate; and
(ii) blending the resulting solid dispersion extrudate with one or more pharmaceutically acceptable excipients,
wherein the solid dispersion extrudate comprises <3% w/w of (S)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide.