(S)-N-(3-6-isopropoxypyridin-3-3YL)-1H-indazol-5-yl)-1-(2-(4-4(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H-yl)-2-oxoethyl)-3(methylthio)pyrrolidine-3-carboxamide compositions for pharmaceutical preparations
A composition comprising (S)—N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-1-(2-(4-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-3-(methylthio)pyrrolidine-3-carboxamide and hypromellose acetate succinate for pharmaceutical preparations, especially capsule preparations.
1. A process for preparing a composition comprising (S)—N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-1-(2-(4-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-3-(methylthio)pyrrolidine-3-carboxamide and hypromellose acetate succinate,
wherein said process comprises the steps of:
a) blending (S)—N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-1-(2-(4-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-3-(methylthio)pyrrolidine-3-carboxamide hydrate form 2 and hypromellose acetate succinate to form a blend,
b) extruding the blend through a twin screw hot melt extruder to form an extrudate,
c) quenching the extrudate on an air cooled conveyor belt or using a chilled roller to form quenched extrudate comprising (S)—N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-1-(2-(4-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-3-(methylthio)pyrrolidine-3-carboxamide amorphous form, and
d) pelletizing the extrudate to form pellets and subsequently milling the pellets to form a ground product.
2. A The process of claim 1 , wherein the weight ratio of (S)—N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-1-(2-(4-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-3-(methylthio)pyrrolidine-3-carboxamide to hypromellose acetate succinate is between about 1:1 and 1:5.
3. A The process of claim 2 , wherein the ratio is about 1:3.