Rapidly disintegrating solid oral dosage forms containing dasatinib
Inventors
Andersson, Per • Meijer, Thomas • Söderberg, Victor
Assignees
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Publication Number
US-11833249-B2
Publication Date
2023-12-05
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 dasatinib solid oral compositions comprising dasatinib 1,2-propanediol solvate and/or dasatinib (R)-1,2-propanediol solvate and dasatinib (S)-1,2-propanediol solvate formulated as a tablet for oral administration. The tablet further comprises at least one pharmaceutically acceptable excipient and a coating layer. The compositions are intended to treat proliferative disorders in patients in need thereof.
A central aspect is that 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. The disclosure frames this as improved dissolution behavior for dasatinib solid oral compositions. The document also addresses variability and bioequivalence challenges associated with dasatinib, including comparison against Sprycel (dasatinib monohydrate).
The disclosure provides representative tablet formulations and dissolution data, and describes single-dose fed/fasted pharmacokinetic crossover data showing bioequivalence. The data compare exposure metrics including Cmax and AUC, with acceptance criteria described using 90% confidence interval ratios. The compositions are also discussed in the context of reference-scaled average bioequivalence (RSABE) approaches, with dissolution figures and bioavailability comparison figures included.
Claims Coverage
The relevant portion identifies one independent claim directed to a treatment method using a specifically defined fast-dissolving dasatinib solvate tablet, supported by dependent claims that narrow the patient population, specify excipient categories, and constrain dasatinib dose equivalences. Across the independent and associated dependents, the inventive features are organized around the solvate form in the tablet, the presence of excipients and a coating layer, and a defined dissolution release criterion under USP Type 2 conditions.
Fast-dissolving dasatinib 1,2-propanediol solvate tablet for treating a proliferative disorder
A method of treating a proliferative disorder in a patient in need thereof by administering a therapeutically effective amount of an oral tablet comprising dasatinib 1,2-propanediol solvate, dasatinib (R)-1,2-propanediol solvate, dasatinib (S)-1,2-propanediol solvate, or a combination thereof; 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.
Claim coverage centers on oral treatment of a proliferative disorder using a tablet containing dasatinib 1,2-propanediol solvate (including specific R or S enantiomers or combinations) and comprising excipients and a coating layer, constrained by a USP Type 2 dissolution release requirement of at least 80% dasatinib in 20 minutes. Dependent features further narrow treated patient subsets, specify excipient categories such as glidants, lubricants, and disintegrants, and provide dasatinib dose-level equivalence groupings.
Stated Advantages
Improved dissolution, including release of at least 80% of dasatinib within 20 minutes under USP Type 2 conditions.
Bioequivalence to Sprycel (dasatinib monohydrate) based on Cmax and AUC metrics with described acceptance criteria (90% confidence interval ratios within limits).
Use of reference-scaled average bioequivalence (RSABE) approaches is described in connection with bioequivalence evaluation.
Documented Applications
Treating proliferative disorders in patients, including Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), with further patient subsets described as having resistance or intolerance to prior therapy including imatinib.
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