Rapidly disintegrating solid oral dosage forms containing dasatinib
Inventors
Andersson, Per • Meijer, Thomas • Söderberg, Victor
Assignees
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Publication Number
US-10869836-B1
Publication Date
2020-12-22
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 a tablet for oral administration comprising dasatinib (S)-1,2-propanediol solvate, at least one pharmaceutically acceptable excipient, and a coating layer. The tablet is defined by a dissolution performance constraint in which the tablet releases at least 80% of the dasatinib within 20 minutes under specified USP Type 2 apparatus conditions in 500 mL of 0.01 M hydrochloric acid at about 37° C. and about 75 RPM. The tablet further includes an amount of dasatinib equivalent to 70 mg dasatinib.
The solution is motivated by a need to address poor aqueous solubility and to provide dissolution performance associated with bioequivalence expectations for dasatinib compared with a reference listed drug comprising dasatinib monohydrate (Sprycel). The disclosed tablet design is intended to reduce sensitivity to fed/fasted state and gastric transit while supporting dissolution and bioequivalence characterization.
Characterization constraints include bioequivalence-related acceptance criteria using 90% confidence interval ranges for ratios of mean AUC and mean Cmax versus a reference listed drug comprising dasatinib monohydrate, including criteria consistent with RSABE when reference variability exceeds a specified CV threshold. Additional constraints include an exclusion rule based on AUC(0-∞) being less than 5% of the reference.
Claims Coverage
The partial content includes one independent claim. The main claim coverage centers on a dasatinib (S)-1,2-propanediol solvate tablet with specified excipient/coating elements and performance constraints for rapid dissolution and dasatinib dose equivalence, with further dependent-claim refinement directed to coating composition/amount and bioequivalence-style characterization limits.
Dasatinib (S)-1,2-propanediol solvate oral tablet with coating
A tablet for oral administration comprising dasatinib (S)-1,2-propanediol solvate, at least one pharmaceutically acceptable excipient, and a coating layer.
Rapid dissolution under USP Type 2 conditions
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.
Dasatinib amount equivalent to 70 mg
The amount of dasatinib is equivalent to 70 mg dasatinib.
Coating layer composition options
The coating layer comprises glyceryl monostearate, hypromellose, poly(vinyl alcohol), polyethylene glycol, polysorbate 80, sodium laurylsulfate, talc, titanium dioxide, or a combination thereof.
Coating layer weight percentage range
The coating layer is present in an amount of from about 1.9% to about 2.2% by weight of the tablet.
Filler/binder selection
The tablet includes at least one filler/binder selected from mannitol, microcrystalline cellulose, lactose, isomalt, or a mixture thereof.
Disintegrant weight percentage range
The tablet comprises at least one disintegrant present in an amount of from about 0.5% to about 10% by weight of the tablet.
Bioequivalence-style 90% confidence interval limits
The tablet exhibits 90% confidence intervals for the ratio of mean AUC(0-∞) and the ratio of mean Cmax versus a reference listed drug comprising dasatinib monohydrate, each between 80% and 125%.
Overall, the claim set coverage focuses on a coated oral tablet formulation containing dasatinib (S)-1,2-propanediol solvate with a rapid dissolution requirement under USP Type 2 testing, a defined dasatinib dose equivalence, and dependent refinements specifying coating composition/amount, excipient classes/amount ranges, and bioequivalence-style 90% confidence interval criteria versus a dasatinib monohydrate reference.
Stated Advantages
Provides rapid dissolution with release of at least 80% of dasatinib within 20 minutes under specified USP Type 2 conditions.
Supports dissolution and bioequivalence characterization relative to a reference listed drug comprising dasatinib monohydrate (Sprycel).
Intended to reduce sensitivity to fed/fasted state and gastric transit.
Documented Applications
Therapeutic use for proliferative disorders including Ph+ chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia.
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