Stable Tablet Formulation containing more than 80% of Imatinib mesylate (19-Feb-2008)

Stable Tablet Formulation containing more than 80% of Imatinib me-
sylate

Imatinib, sold unter the tradename Glivec™, is an inhibitor of the
Tyrosine kinase, established in the treatment of chronic myeloid
leukemia and gastrointestinal tumors. Tablet formulations contain
119.5 mg and 478 mg respectively of the imatinib mesylate, corre-
sponding to 100 mg and 400 mg respectively of imatinib base. A
stable formulation containing 30 to 80% of imatinib or a pharma-
ceutically acceptable salt thereof is described and claimed in the
European Patent EP 1,501,485 B1, comprising a wet granulation
process with different excipients and subsequent compression into
tablets.

Manufacturing and dissolution of tablet formulations containing
more than 80% of imatinib mesylate based on the total weight of
the tablet were manufactured and tested. It was found that the
compressibility of the API itself is acceptable to reduce the
amount of additional tablet ingredients to a level of 2 to 13 %.
The use of a dry binder (Povidone, Hypromellose, Hydroxypropylcel-
lulose) in amounts of about 2% to 10% of the tablet weight was
sufficient to receive tablets with sufficient hardness without
significantly affecting the disintegration and dissolution. Stable
tablet formulations further included a superdisintegrant (e.g.
crosspovidone 2 to 10%), a lubricant (e.g. magnesium stearate 0.2
to 1.5 %) and a glidant (e.g. silicon dioxide colloidal 0.1 to
1.0%).

Granules and table...