Pharmaceutical formulation of palbociclib and a preparation method thereof

Abstract

The present invention belongs to the pharmaceutical field, and in particular, it relates to a pharmaceutical formulation of palbociclib and a preparation method thereof. The pharmaceutical formulation comprises palbociclib, an acidic auxiliary material, and optionally a hydrophilic high-molecular material, which has better solubility and in vitro dissolution property as compared with the conventional formulation and can be used for enhancing in vivo absorption and bioavailability of palbociclib.

1 - 20 . (canceled) 
     
     
         21 . A method of making a composition comprising an amorphous solid dispersion, comprising:
 combining palbociclib or a pharmaceutically acceptable salt thereof, an acidic auxiliary material, a solvent, and a hydrophilic high-molecular weight material;   dissolving or dispersing the palbociclib or a pharmaceutically acceptable salt thereof, and   removing the solvent.   
     
     
         22 . The method of  claim 21 , wherein the acidic auxiliary material is selected from the group consisting of tartaric acid, fumaric acid, succinic acid, citric acid, lactic acid, malic acid, an aliphatic sulfonic acid, an aromatic sulfonic acid, and combinations thereof. 
     
     
         23 . The method of  claim 21 , wherein the concentration of the palbociclib or the pharmaceutically acceptable salt thereof in the solvent is 50 mg/ml or more. 
     
     
         24 . The method of  claim 21 , wherein the concentration of the palbociclib or the pharmaceutically acceptable salt thereof in the solvent is up to 50 mg/ml. 
     
     
         25 . The method of  claim 21 , wherein the removing the solvent comprises evaporating the solvent by vacuum drying, heating drying, freeze drying, or combinations thereof. 
     
     
         26 . The method of  claim 21 , wherein the solvent comprises water, ethanol, acetone, or a mixture thereof. 
     
     
         27 . The method of  claim 21 , wherein a mass ratio of the acidic auxiliary material to the palbociclib or the pharmaceutically acceptable salt thereof ranges from 0.5:1 to 5:1. 
     
     
         28 . The method of  claim 22 , wherein the acidic auxiliary material is tartaric acid. 
     
     
         29 . The method of  claim 21 , wherein the hydrophilic high-molecular weight material is one or more selected from the group consisting of povidone K30, copovidone VA64, Soluplus, hydroxypropylmethylcellulose E5, hydroxypropylmethylcellulose acetate succinate, hydroxypropyl-P-cyclodextrin and sulfobutyl ether-P-cyclodextrin. 
     
     
         30 . The method of  claim 21 , wherein a mass ratio of the hydrophilic high-molecular weight to the palbociclib or the pharmaceutically acceptable salt thereof ranges from 0.1:1 to 10:1. 
     
     
         31 . The method of  claim 21 , wherein a mass ratio of the hydrophilic high-molecular weight to the palbociclib or the pharmaceutically acceptable salt thereof ranges from 0.1:1 to 10:1 and wherein a mass ratio of the acidic auxiliary material to the palbociclib or the pharmaceutically acceptable salt thereof ranges from 0.5:1 to 5:1. 
     
     
         32 . The method of  claim 22 , wherein the acidic auxiliary material is an aliphatic sulfonic acid. 
     
     
         33 . The method of  claim 32 , wherein the aliphatic sulfonic acid is selected from the group consisting of methanesulfonic acid, ethanesulfonic acid and isethionic acid, and the aromatic sulfonic acid is selected from the group consisting of benzenesulfonic acid and p-toluenesulfonic acid. 
     
     
         34 . The method of  claim 21 , wherein the composition is orally administered. 
     
     
         35 . The method of  claim 21 , wherein the palbociclib or the pharmaceutically acceptable salt thereof is present in an amount of 25 to 500 mg. 
     
     
         36 . The method of  claim 21 , wherein the composition is in the dosage form of a tablet or a capsule. 
     
     
         37 . A composition comprising an amorphous solid dispersion, wherein the composition is made according to the method of  claim 21 . 
     
     
         38 . A method of treating breast cancer, comprising administering to a subject having breast cancer the composition of  claim 37 . 
     
     
         39 . A method of making a composition comprising an amorphous solid dispersion, comprising:
 (a) pulverizing palbociclib or a pharmaceutically acceptable salt thereof and thereby obtaining pulverized palbociclib at a particle size to D90 at 20 μm or less;   (b) mixing the pulverized palbociclib with an acidic auxiliary material;   (c) co-pulverizing the mixture from (b) and thereby obtain a pulverized mixture of palbociclib and acidic auxiliary material at a particle size to D90 at 20 μm or less; and   wherein the method comprises adding another pharmaceutically acceptable excipient.   
     
     
         40 . A method of improving in vitro dissolution and in vivo bioavailability of palbociclib, comprising
 (a) pulverizing palbociclib or a pharmaceutically acceptable salt thereof and thereby obtaining pulverized palbociclib at a particle size to D90 at 20 μm or less;   (b) mixing the pulverized palbociclib with an acidic auxiliary material; and   (c) co-pulverizing the mixture from (b) and thereby obtain a pulverized mixture of palbociclib and acidic auxiliary material at a particle size to D90 at 20 μm or less.