Rapidly disintegrating solid oral dosage forms containing dasatinib
Inventors
Andersson, Per • Meijer, Thomas • Söderberg, Victor
Assignees
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Publication Number
US-10799459-B1
Publication Date
2020-10-13
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 rapidly disintegrating oral solid dosage forms, in particular tablets for oral administration, that comprise dasatinib 1,2-propanediol solvate and at least one pharmaceutically acceptable excipient, and additionally include a coating layer. The dasatinib 1,2-propanediol solvate is described in stereoisomeric form as dasatinib (R)-1,2-propanediol solvate and/or dasatinib (S)-1,2-propanediol solvate, including combinations of such solvates.
The problem addressed is improving dissolution and performance of dasatinib, which is characterized as having pH-dependent solubility and weak base behavior associated with BCS II. The disclosed solution specifies that the tablet releases at least 80% of the dasatinib within 20 minutes under defined USP Type 2 conditions in 500 mL of 0.01 M hydrochloric acid at about 37°C and about 75 RPM.
The invention further supports regulatory-style bioequivalence approaches for the oral tablet when compared to a dasatinib reference listed drug containing dasatinib monohydrate (Sprycel® 100 mg). Bioequivalence acceptance is expressed using 90% confidence interval ranges for ratios involving mean AUC and mean Cmax, and additional reference-scaled average bioequivalence criteria are described for highly variable drugs.
Claims Coverage
The supplied independent claim specifies 2 inventive features. Dependent claim coverage further refines solvate stereoisomer selection, coating composition and amount, and quantitative bioequivalence metrics against a dasatinib monohydrate reference, including RSABE criteria.
Tablet comprising dasatinib 1,2-propanediol solvate with excipient and coating layer
A tablet for oral administration 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.
Rapid dissolution release at least 80% within 20 minutes under USP Type 2 conditions
The tablet releases at least 80% of the dasatinib within 20 minutes when tested in a USP Type 2 in 500 mL of 0.01 M hydrochloric acid at about 37°C and about 75 RPM.
Claim coverage centers on a tablet formulation containing dasatinib 1,2-propanediol solvate(s) and at least one pharmaceutically acceptable excipient, with a performance requirement of releasing at least 80% of dasatinib within 20 minutes under specified USP Type 2 dissolution conditions. Dependent claims add refinements including solvate stereoisomer selection, coating layer component materials and amount, and quantitative bioequivalence criteria with optional RSABE criteria.
Stated Advantages
Rapid release/dissolution performance, with the tablet releasing at least 80% of the dasatinib within 20 minutes under specified USP Type 2 conditions.
Comparable exposure to a reference listed drug containing dasatinib monohydrate using stated bioequivalence criteria based on 90% confidence intervals for AUC and Cmax.
Optional reference-scaled average bioequivalence (RSABE) criteria are described for highly variable drugs.
Documented Applications
Treating a proliferative disorder by administering a therapeutically effective amount of the claimed composition to adults with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase, including adults newly diagnosed; and to adults with Ph+ CML in chronic, accelerated, or myeloid or lymphoid blast phases with resistance or intolerance to prior therapy including imatinib.
Treating a proliferative disorder by administering a therapeutically effective amount of the claimed composition to adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
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