Pharmaceutical formulation of palbociclib and a preparation method thereof
Inventors
Wang, Zeren • Xu, Jun • Qu, Long
Assignees
Shenzhen Hlk Pharmaceuticals Co Ltd • Shenzhen Pharmacin Co Ltd
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Publication Number
US-10813937-B2
Publication Date
2020-10-27
Expiration Date
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.
Core Innovation
The invention relates to a palbociclib formulation comprising an amorphous solid dispersion in which palbociclib or a pharmaceutically acceptable salt thereof is present with tartaric acid and a hydrophilic high-molecular weight material, where the components are in an amorphous state. The formulation is intended to improve aqueous solubility and in vitro dissolution, thereby improving in vivo bioavailability.
The solid-state strategy emphasizes forming an amorphous solid dispersion by solvent removal after co-dissolving palbociclib and tartaric acid, with subsequent confirmation of amorphous or solid-state changes using XRPD. The examples describe that combining the amorphous solid dispersion with particle-size reduction can increase dissolution and dynamic solubility.
The amorphous solid dispersion composition is described for oral solid dosage forms including a tablet or a capsule. The acidic auxiliary material is tartaric acid, and the hydrophilic high-molecular weight material is selectable from materials such as povidone K30, copovidone VA64, Soluplus, HPMC-E5, HPMC-AS-HF, and cyclodextrin derivatives.
Claims Coverage
The independent claims cover an amorphous solid dispersion composition with 3 core components in an amorphous state: palbociclib or a pharmaceutically acceptable salt thereof, tartaric acid, and a hydrophilic high-molecular weight material. The dependent claims refine the composition by constraining palbociclib amount, fixing tartaric acid at a specific quantity, specifying acceptable hydrophilic high-molecular materials, optionally limiting to copovidone VA64, and restricting dosage form to tablet or capsule.
Amorphous solid dispersion with palbociclib, tartaric acid, and hydrophilic high-molecular material
A composition comprising an amorphous solid dispersion wherein palbociclib or a pharmaceutically acceptable salt thereof is present in an amount of 25 to 500 mg, tartaric acid, and a hydrophilic high-molecular weight material, with the components in an amorphous state.
Palbociclib amount constraints
The composition wherein palbociclib or a pharmaceutically acceptable salt thereof is present in an amount selected from specified mg values.
Tartaric acid fixed amount
The composition wherein tartaric acid is present in an amount of 200 mg.
Hydrophilic high-molecular weight material selection list
The composition wherein the hydrophilic high-molecular weight material is selected from povidone K30, copovidone VA64, Soluplus, hydroxypropylmethylcellulose E5, hydroxypropylmethylcellulose acetate succinate, hydroxypropyl-β-cyclodextrin and sulfobutyl ether-β-cyclodextrin.
Copovidone VA64 as the hydrophilic high-molecular material
The composition wherein the hydrophilic high-molecular weight material is copovidone VA64.
Tablet or capsule dosage form
The composition provided in a dosage form selected from a tablet or a capsule.
Overall claim coverage centers on an amorphous solid dispersion of palbociclib or a pharmaceutically acceptable salt thereof with tartaric acid and a hydrophilic high-molecular weight material in an amorphous state, with dependent claims refining the palbociclib amount, fixing tartaric acid at 200 mg, defining acceptable hydrophilic high-molecular excipients, and limiting dosage form to tablets or capsules.
Stated Advantages
Improving aqueous solubility and in vitro dissolution to support improved in vivo bioavailability.
Dissolution improvement compared with a reference condition and with particle-size reduction.
Increase in dynamic solubility.
Retention of amorphous tartaric acid after storage.
Documented Applications
Oral solid dosage forms comprising the amorphous solid dispersion formulation, including tablets and capsules.
Use in contexts described with palbociclib and cyclin-dependent kinase (CDK4/6) inhibition, including reference to breast cancer in the provided description.
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