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-11464779-B2
Publication Date
2022-10-11
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 an oral palbociclib formulation provided as an amorphous solid dispersion. The amorphous solid dispersion comprises palbociclib or a pharmaceutically acceptable salt, an acidic auxiliary material, and a hydrophilic high-molecular weight material, and the palbociclib is present in an amorphous state together with the acidic auxiliary material and the hydrophilic high-molecular weight material.
The acidic auxiliary material comprises at least two pharmaceutically acceptable acids, wherein the pharmaceutically acceptable salt of palbociclib comprises one of the at least two pharmaceutically acceptable acids. The formulation is described with multi-acid options, including tartaric acid, fumaric acid, succinic acid, citric acid, lactic acid, malic acid, dihydric phosphate, bisulfate, hydrochloric acid, sulfuric acid, and phosphoric acid.
The approach is directed to improving solubility, dissolution, bioavailability, and amorphous-state stability of palbociclib after formulation. Processing features described include use of palbociclib with reduced particle size and formation of the amorphous solid dispersion by solvent co-dissolving followed by solvent removal, with analytical evaluation including dissolution/dynamic solubility and XRPD.
Claims Coverage
The document includes two independent claims. The inventive features center on an amorphous solid dispersion composition with a multi-acid auxiliary system and a hydrophilic high-molecular weight material, and a breast-cancer treatment method by administering that composition.
An amorphous solid dispersion composition with multi-acid acidic auxiliary material and hydrophilic high-molecular weight material
An amorphous solid dispersion comprising palbociclib or a pharmaceutically acceptable salt thereof, an acidic auxiliary material comprising at least two pharmaceutically acceptable acids wherein the pharmaceutically acceptable salt of the palbociclib comprises one of the at least two pharmaceutically acceptable acids, and a hydrophilic high-molecular weight material, wherein the amorphous solid dispersion is in an amorphous state.
A method for treating breast cancer by administering an oral pharmaceutical composition with the specified amorphous solid dispersion
A method for treating breast cancer comprising administering to a subject having breast cancer a pharmaceutical composition comprising an amorphous solid dispersion in an amorphous state comprising palbociclib or a pharmaceutically acceptable salt thereof, an acidic auxiliary material comprising at least two pharmaceutically acceptable acids wherein the pharmaceutically acceptable salt of the palbociclib comprises one of the at least two pharmaceutically acceptable acids, and a hydrophilic high-molecular weight material.
Across the independent claims, the core claim coverage is for an amorphous solid dispersion where palbociclib, or its pharmaceutically acceptable salt, is present in the amorphous state together with an acidic auxiliary material defined by at least two pharmaceutically acceptable acids and a hydrophilic high-molecular weight material, and a method of breast-cancer treatment by administering that pharmaceutical composition.
Stated Advantages
Improved solubility, dissolution, bioavailability.
Retention of the acid in amorphous form over storage.
Documented Applications
Treating breast cancer by administering a pharmaceutical composition comprising the specified amorphous solid dispersion.
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