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
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10894049-B2
Publication Date
2021-01-19
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 pharmaceutical composition for treating breast cancer that includes an amorphous solid dispersion. The amorphous solid dispersion comprises palbociclib or a pharmaceutically acceptable salt thereof in an amorphous state together with tartaric acid and a hydrophilic high-molecular weight material, also in an amorphous state.
The disclosed approach addresses poor dissolution and solubility associated with palbociclib by forming an amorphous solid dispersion in which the acidic auxiliary tartaric acid can convert to an amorphous state and remain stable. The composition combines palbociclib and tartaric acid with a hydrophilic high-molecular weight material to maintain the amorphous nature over time under storage conditions.
Improved dissolution and dynamic solubility are reported for the amorphous solid dispersion compared with prior palbociclib formulations. The document reports increased cumulative dissolution and higher dynamic solubility for formulations that include an acidic auxiliary such as tartaric acid, and describes the composition in the context of treating breast cancer, including ER-positive and HER-2-negative breast cancer.
Claims Coverage
The document includes one independent claim directed to a method for treating breast cancer by administering a pharmaceutical composition containing a specific amorphous solid dispersion. The independent claim is characterized by three inventive structural elements in an amorphous state: palbociclib or a pharmaceutically acceptable salt, tartaric acid, and a hydrophilic high-molecular weight material.
Amorphous solid dispersion for breast cancer treatment
A pharmaceutical composition comprising an amorphous solid dispersion, wherein the amorphous solid dispersion comprises palbociclib or a pharmaceutically acceptable salt thereof, tartaric acid, and a hydrophilic high-molecular weight material in an amorphous state.
Palbociclib dosage range within the composition
The method where palbociclib or a pharmaceutically acceptable salt thereof is present in an amount of 25 to 500 mg.
Fixed tartaric acid amount
The method where tartaric acid is present at an amount of 200 mg.
Selected hydrophilic high-molecular weight material excipients
The method where 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.
Oral administration of the amorphous solid dispersion
The method further comprises orally administering an amorphous solid dispersion.
Treatment restricted to ER-positive breast cancer subjects
The method further includes diagnosing a subject as having ER-positive breast cancer.
Overall claim coverage centers on administering, for breast cancer treatment, a pharmaceutical composition containing an amorphous solid dispersion in which palbociclib or a pharmaceutically acceptable salt is combined in an amorphous state with tartaric acid and a hydrophilic high-molecular weight material. Dependent claims further narrow palbociclib and tartaric acid amounts, restrict the hydrophilic high-molecular weight excipients to listed materials, specify oral administration, and limit the treated subject class by diagnosis of ER-positive breast cancer.
Stated Advantages
Improved dissolution and dynamic solubility versus prior palbociclib formulations.
Increased cumulative dissolution for formulations containing an acidic auxiliary such as tartaric acid.
Higher dynamic solubility for the disclosed amorphous solid dispersion compared with palbociclib API alone.
Maintained amorphous stability over one week at 40°C/75% RH.
Documented Applications
Treating breast cancer by administering the disclosed pharmaceutical composition including an amorphous solid dispersion.
Treating ER-positive and HER-2-negative breast cancer.
Interested in licensing this patent?