Pralsetinib pharmaceutical compositions
The present disclosure relates to pharmaceutical composition comprising 1) an amorphous solid dispersion comprising pralsetinib, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable hydrophilic polymer; and 2) an effervescent couple; and crystalline forms of pralsetinib and pralsetinib hydrochloride salt, which are useful as a RET selective inhibitors. The present disclosure also provides pharmaceutically acceptable compositions comprising the crystalline forms and methods of using said compositions in the treatment of various disorders.
1 . An immediate release oral dosage form comprising:
a) an amorphous solid dispersion comprising: pralsetinib, or a pharmaceutically acceptable salt thereof, and hydroxypropyl methylcellulose E3, wherein the pralsetinib or an equivalent amount of pharmaceutically acceptable salt thereof and the hydroxypropyl methyl cellulose E3 are in about a 1:1 weight ratio;
b) an effervescent couple comprising about 3 to about 13 w/w % citric acid and about 7 to about 30 w/w % sodium bicarbonate; wherein w/w % is based on the total weight of the oral dosage form;
c) a diluent; and
d) moisture scavenger and a lubricant,
wherein the immediate release oral dosage form comprises the amorphous solid dispersion from about 25% to about 65% percent by weight of the immediate release oral dosage form, based on the total weight of the oral dosage form, and
the immediate release oral dosage form is a tablet or a capsule.
2 . The oral dosage form of claim 1 , wherein the amorphous solid dispersion comprises about 30 mg, about 50 mg, about 60 mg or about 100 mg of pralsetinib or an equivalent amount of a pharmaceutically acceptable salt thereof.
3 . The composition of claim 1 , wherein the dosage form is a capsule, wherein the capsule disintegrates in about 7 to 15 minutes using USP <701>, with Basket Type A and a disc with a maintained temperature at 37° C.±2° C.
4 . The composition of claim 1 , wherein the dosage form is a capsule, wherein at least 80% of the pralsetinib is released in about 120 minutes using USP <711> with a Type 2 Apparatus with a media containing 900 mL pH 6.8 sodium phosphate buffer with 0.5% CTAB and a paddle speed of 75 rpm±2 rpm.
5 . An immediate release oral dosage form comprising:
a) about 55 w/w % of an amorphous solid dispersion comprising: pralsetinib, or a pharmaceutically acceptable salt thereof, and hydroxypropyl methylcellulose E3, wherein the pralsetinib or an equivalent amount of pharmaceutically acceptable salt thereof and the hydroxypropyl methyl cellulose E3 are in about a 1:1 weight ratio;
b) an effervescent couple comprising about 9 w/w % citric acid and about 22 w/w % sodium bicarbonate;
c) about 9 w/w % microcrystalline cellulose;
d) about 4 w/w % pregelatinized starch; and
e) about 1 w/w % magnesium stearate,
wherein w/w % is based on the total weight of the oral dosage form, and the immediate release oral dosage form is a tablet or a capsule.