Pharmaceutical compositions of cabozantinib
Pharmaceutical compositions are provided, which comprise cabozantinib or pharmaceutically acceptable salts thereof, and at least one pharmaceutically acceptable excipient, wherein the inventive compositions exhibit enhanced bioavailability compared to the currently marketed or commercially available formulations. The present invention also provides manufacturing processes thereof and use of the said inventive compositions for the prevention, treatment or prophylaxis of disorders in human patients in need thereof. The present invention relates to oral pharmaceutical compositions of cabozantinib, methods for their administration, processes for their production, and use of these compositions for treatment of diseases treatable by cabozantinib.
1. A pharmaceutical composition suitable for oral administration comprising cabozantinib in the form of an amorphous solid dispersion and at least one pharmaceutically acceptable excipient,
wherein said amorphous solid dispersion consists of
a) cabozantinib or a pharmaceutically acceptable salt thereof;
b) a pharmaceutically acceptable carrier selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate (HPMC-AS), polyvinyl pyrrolidine and vinyl acetate (PVP/VA) copolymer, hydroxypropyl methylcellulose phthalate (HPMCP), and mixtures thereof;
c) a pore-forming agent selected from group consisting of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), lactose, mannitol and mixtures thereof; and
d) polyethylene glycol as a plasticizer.
2. The pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable salt of cabozantinib is cabozantinib(S)-malate.
3. The pharmaceutical composition according to claim 1 , wherein a weight percentage of the plasticizer ranges from 4 to 8% w/w of the pharmaceutical composition.
4. The pharmaceutical composition according to claim 1 , wherein a weight percentage of the plasticizer ranges from 4 to 14% w/w of the amorphous solid dispersion.
5. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a tablet or a capsule.
6. The pharmaceutical composition according to claim 1 , wherein said composition provides about 30% enhanced Cmax and about 30% enhanced AUC 0-72 hr , compared to a drug product corresponding to National Drug Code Number 42388-023 and NDA 208692 having the same therapeutically effective amount of cabozantinib, following oral administration in human subjects under fasting condition.