Crystalline forms of a brutons tyrosine kinase inhibitor

Inventors

Purro, Norbert • Smyth, Mark S. • Goldman, Erick • Wirth, David D.

Assignees

Pharmacyclics LLC

Abstract

Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including crystalline forms, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Core Innovation

The invention relates to an oral pharmaceutical formulation that includes about 140 mg of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one for oral administration. The formulation further comprises one or more diluents, one or more surfactants, and one or more lubricants, and is positioned as a dosage form for oral delivery of Compound 1 in defined excipient combinations.

The disclosed oral pharmaceutical preparations encompass hard or soft sealed gelatin capsules, tablets, powders, solid dispersions or solutions, and controlled-release or pulsatile-release forms. The document further includes enteric-coated delayed-release systems and microencapsulated and multilayer plasticized formulations, as well as suspensions and packaging or kit presentations, associated with pharmaceutically acceptable excipients selected from diluents, binders, surfactants, lubricants, disintegrants, and plasticizers.

The described material forms include crystalline forms of Compound 1, solvates, solvated forms, and pharmaceutically acceptable salts, including acid addition salts. The crystalline forms are characterized using XRPD peak positions, IR spectra, DSC and TGA thermograms, solubility, melting/endotherm behavior, and stability under humidity and temperature storage, with specific solvate examples including a MIBK solvate and solvent-related solvates.

Claims Coverage

The document provides at least one independent claim covering an oral pharmaceutical formulation of Compound 1 together with excipient classes. The inventive features are centered on formulation composition for oral administration, including the specific active amount and the combination of diluents, surfactants, and lubricants, with dependent claims further constraining excipient selection and quantities.

Overall, the independent claim is directed to a specific oral formulation architecture for Compound 1 containing about 140 mg of the active with diluents, surfactants, and lubricants. Dependent claim elements refine this by adding wt% constraints and narrowing named choices for surfactants and lubricants, and by specifying a hard gelatin capsule dosage form.

Stated Advantages

Documented Applications