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-10449195-B2
Publication Date
2019-10-22
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 weight 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 solid formulation of palbociclib designed as a single amorphous solid dispersion. The single amorphous solid dispersion comprises palbociclib or a pharmaceutically acceptable salt, tartaric acid, and a hydrophilic high-molecular weight material, in which the palbociclib and tartaric acid are dispersed within the hydrophilic high-molecular weight material and are in an amorphous state.
The formulation combines an acidic auxiliary material with a hydrophilic high-molecular weight polymer or carrier to improve palbociclib solubility and oral performance. The hydrophilic high-molecular weight material is exemplified by povidone K30, copovidone VA64, Soluplus, hydroxypropylmethylcellulose derivatives, and cyclodextrin derivatives, and the tartaric acid-to-palbociclib mass ratio ranges from 0.5:1 to 5:1.
The document describes approaches intended to enhance solubility and bioavailability by increasing amorphous content and controlling solid-state characteristics. These approaches include reducing palbociclib particle size to a specified D90 range and forming amorphous solid dispersions by co-dissolution followed by solvent removal, with an emphasis on maintaining amorphous acid during storage.
Claims Coverage
The independent claim is directed to a single amorphous solid dispersion having three core components: palbociclib or a pharmaceutically acceptable salt, tartaric acid, and a hydrophilic high-molecular weight material, where palbociclib and tartaric acid are dispersed within the hydrophilic high-molecular weight material and are in an amorphous state. The claims further specify quantitative mass-ratio constraints and selected carrier materials.
Single amorphous solid dispersion with dispersed amorphous palbociclib and tartaric acid
A single amorphous solid dispersion comprising palbociclib or a pharmaceutically acceptable salt, tartaric acid, and a hydrophilic high-molecular weight material, wherein the palbociclib and the tartaric acid are dispersed within the hydrophilic high-molecular weight material and wherein the palbociclib and tartaric acid are in an amorphous state.
Tartaric acid to palbociclib mass ratio
The mass ratio of the tartaric acid to the palbociclib or the pharmaceutically acceptable salt thereof ranges from 0.5:1 to 5:1.
Selected hydrophilic high-molecular weight materials
The hydrophilic high-molecular weight material is selected from povidone K30, copovidone VA64, Soluplus, hydroxypropylmethylcellulose E5, hydroxypropylmethylcellulose acetate succinate, hydroxypropyl-β-cyclodextrin, or sulfobutyl ether-β-cyclodextrin.
Hydrophilic high-molecular weight material to palbociclib mass ratio constraint
The mass ratio of a hydrophilic high-molecular weight material to palbociclib or the pharmaceutically acceptable salt falls between 0.1:1 and 10:1.
Optional inorganic acid component
The single amorphous solid dispersion further comprises a pharmaceutically acceptable inorganic acid selected from hydrochloric acid, sulfuric acid, phosphoric acid, or combinations thereof.
Overall, the claim coverage centers on a single amorphous solid dispersion in which palbociclib or its pharmaceutically acceptable salt and tartaric acid are dispersed within a specified hydrophilic high-molecular weight material in an amorphous state, with quantitative mass-ratio constraints and further dependent refinements specifying particular polymers or carriers and optional inorganic acid.
Stated Advantages
Improves solubility of palbociclib, including improved in vitro dissolution and increased dynamic solubility.
Improves in vivo bioavailability.
Improves dissolution performance versus prior formulations, as described by dissolution and dynamic solubility results.
Documented Applications
Oral solid formulation of palbociclib for improved solubility, in vitro dissolution, and in vivo bioavailability, including for breast cancer as referenced in the document context.
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