Rapidly disintegrating solid oral dosage forms containing dasatinib
Inventors
Andersson, Per • Meijer, Thomas • Soderberg, Victor
Assignees
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Publication Number
US-10874613-B1
Publication Date
2020-12-29
Expiration Date
Abstract
The instant application relates to the field of pharmaceutical compositions comprising dasatinb. Furthermore, the instant application relates to a method of treating proliferative disorders in a patient in need thereof, comprising administering a therapeutically effective amount of said compositions.
Core Innovation
The invention relates to orally administered dasatinib solid dosage forms intended to achieve rapid dissolution and bioequivalence to Sprycel. Dasatinib is described as a weakly basic drug and a BCS Class II compound, for which variability and fed/fasted effects are problematic for demonstrating bioequivalence.
The invention addresses the need to reduce variability and to mitigate fed/fasted effects by formulating dasatinib as a 1,2-propanediol solvate in solid oral dosage forms. The described formulations include tablets and other oral forms comprising dasatinib 1,2-propanediol solvate, including (S)-1,2-propanediol solvate and also (R)-1,2-propanediol solvate.
In the claimed tablet embodiment, the tablet includes dasatinib (S)-1,2-propanediol solvate, at least one pharmaceutically acceptable excipient, and a coating layer. The tablet is characterized by a dissolution performance criterion and, in additional embodiments, by pharmacokinetic/bioequivalence acceptance criteria comparing oral administration to a reference listed drug comprising dasatinib monohydrate.
Claims Coverage
The partial content identifies one independent claim focused on a specific tablet composition and performance criteria. The dependent claims refine excipient/coating details and add pharmacokinetic/bioequivalence and patient-treatment scope features, including an indication tied to Philadelphia chromosome-positive leukemia populations.
S-enantiomer dasatinib 1,2-propanediol solvate tablet with coating layer and rapid dissolution
A tablet for oral administration comprising dasatinib (S)-1,2-propanediol solvate, at least one pharmaceutically acceptable excipient, and a coating layer, wherein the tablet releases at least 80% of the dasatinib within 20 minutes when tested in a USP Type 2 apparatus in 500 mL of 0.01 M hydrochloric acid at about 37°C and about 75 RPM, and wherein the amount of dasatinib is equivalent to 20 mg dasatinib.
Across the identified claim family, the core coverage is a coated oral tablet formulation containing dasatinib (S)-1,2-propanediol solvate with rapid dissolution, further refined by coating-layer composition/loading and, in dependent embodiments, pharmacokinetic/bioequivalence criteria versus a reference listed drug containing dasatinib monohydrate and inclusion of Philadelphia chromosome-positive leukemia treatment populations.
Stated Advantages
Rapid dissolution performance, characterized by at least 80% dasatinib release within 20 minutes under USP Type 2 test conditions.
Bioequivalence performance characterized by 90% confidence interval ratios for AUC and Cmax within 80–125% versus a reference listed drug comprising dasatinib monohydrate.
Reduced variability and mitigation of fed/fasted effects.
Documented Applications
Treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) using a therapeutically effective amount of a composition according to claim 1, including patient populations resistant or intolerant to prior therapy including imatinib.
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