Rapidly disintegrating solid oral dosage forms containing dasatinib
Inventors
Andersson, Per • Meijer, Thomas • Söderberg, Victor
Assignees
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Publication Number
US-10894017-B1
Publication Date
2021-01-19
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 disclosed work addresses poor aqueous solubility of dasatinib and pH-dependent dissolution, including that dasatinib is a BCS II highly variable drug. The document describes a need for a dasatinib drug product with reduced sensitivity to fed/fasted gastric transit, together with improved dissolution and bioequivalence versus Sprycel (dasatinib monohydrate).
To meet this need, the disclosure provides rapidly disintegrating solid oral dosage forms in tablet form that include dasatinib 1,2-propanediol solvate, including dasatinib (S)-1,2-propanediol solvate and dasatinib (R)-1,2-propanediol solvate options. The described tablet includes pharmaceutically acceptable excipients and a coating layer, and is characterized by a rapid dissolution profile under USP Type 2 apparatus conditions in 0.01 M hydrochloric acid.
The document further characterizes performance using bioequivalence criteria and dissolution targets, including bioequivalence framework (RSABE) and 90% confidence intervals for ratios of mean AUC and mean Cmax relative to a reference listed drug comprising dasatinib monohydrate. Representative formulations are described as tablets that release at least 80% of the dasatinib within 20 minutes in USP Type 2 (apparatus II) at 37°C and 75 rpm, and comparative PK results are reported for fasted and fed conditions.
Claims Coverage
The independent claim identified is clm-00001. It defines one core inventive tablet concept together with performance-linked dissolution requirements and dosage amount equivalence, and several dependent claims refine excipient and coating-layer details and add bioequivalence characterization metrics.
Rapidly releasing oral tablet of dasatinib (S)-1,2-propanediol solvate
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; wherein the amount of dasatinib is equivalent to 100 mg dasatinib.
Overall claim coverage centers on a coated oral tablet containing dasatinib (S)-1,2-propanediol solvate that meets a defined rapid dissolution release requirement under USP Type 2 conditions and includes dosage equivalence to 100 mg dasatinib, with dependent claims refining coating and excipient composition and adding bioequivalence metrics.
Stated Advantages
Reduced sensitivity to fed/fasted gastric transit.
Improved dissolution.
Improved bioequivalence versus Sprycel (dasatinib monohydrate).
Documented Applications
Use of tablets for oral administration in connection with bioequivalence comparisons versus Sprycel (dasatinib monohydrate), including reported fasted and fed PK crossover study results in healthy male subjects.
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