Formulations of a bruton's tyrosine kinase inhibitor
View Patent ↗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 novel pharmaceutical formulations 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.
1. A solid dispersion formulation, wherein the formulation comprises
a) about 49 to about 51% w/w of 50% active spray-dried ibrutinib, wherein ibrutinib is a compound of formula (I),
b) about 16 to about 18% w/w of lactose,
c) about 24 to about 26% w/w of microcrystalline cellulose,
d) about 5 to about 7% w/w of croscarmellose sodium,
e) about 0.8 to about 1.2% w/w of colloidal silicon dioxide, and
f) about 0.2 to about 0.8% w/w of magnesium stearate;
and wherein the 50% active spray-dried ibrutinib is a spray-dried ibrutinib composition comprising about 50% w/w of ibrutinib dispersed into a polymer matrix; and the polymer in the polymer matrix is hydroxypropyl methyl cellulose acetate succinate (HPMCAS).
2. A solid dispersion formulation, wherein the formulation comprises
a) about 52 to about 54% w/w of 20% active spray-dried ibrutinib, wherein ibrutinib is a compound of formula (I),
b) about 13 to about 15% w/w of lactose,
c) about 24 to about 26% w/w of microcrystalline cellulose,
d) about 5 to about 7% w/w of croscarmellose sodium,
e) about 0.8 to about 1.2% w/w of colloidal silicon dioxide, and
f) about 0.4 to about 0.6% w/w of magnesium stearate;
and wherein the 20% active spray-dried ibrutinib is a spray-dried ibrutinib composition comprising about 20% w/w of ibrutinib dispersed into a polymer matrix; and the polymer in the polymer matrix is hydroxypropyl methyl cellulose acetate succinate (HPMCAS).
3. A solid dispersion formulation, wherein the formulation comprises
a) about 49 to about 51% w/w of 50% active spray-dried ibrutinib, wherein ibrutinib is a compound of formula (I),
b) about 16 to about 18% w/w of lactose,
c) about 24 to about 26% w/w of microcrystalline cellulose,
d) about 5 to about 7% w/w of croscarmellose sodium,
e) about 0.8 to about 1.2% w/w of colloidal silicon dioxide, and
f) about 0.2 to about 0.8% w/w of magnesium stearate;
and wherein the 50% active spray-dried ibrutinib is a spray-dried ibrutinib composition comprising about 50% w/w of ibrutinib dispersed into a polymer matrix; and the polymer in the polymer matrix is polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®).
4. A method for treating a cancer comprising administering to a patient in need thereof a therapeutically effective amount of the solid dispersion formulation of claim 1 , wherein the cancer is selected from chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and Waldenstrom macroglobulinemia.
5. A method for treating a cancer comprising administering to a patient in need thereof a therapeutically effective amount of the solid dispersion formulation of claim 2 , wherein the cancer is selected from chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and Waldenstrom macroglobulinemia.
6. A method for treating a cancer comprising administering to a patient in need thereof a therapeutically effective amount of the solid dispersion formulation of claim 3 , wherein the cancer is selected from chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and Waldenstrom macroglobulinemia.