Pharmaceutical compositions comprising nilotinib
Inventors
Fischer, Andreas • Andersson, Thomas
Assignees
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Publication Number
US-12419892-B2
Publication Date
2025-09-23
Expiration Date
Abstract
Disclosed herein is a composition comprising: an amorphous solid dispersion (ASD) comprising nilotinib and at least one polymeric stabilizing and matrix-forming component; and at least one solid organic acid in admixture with the ASD, and uses thereof in the treatment of proliferative disorder.
Core Innovation
A particulate amorphous solid dispersion (ASD) comprises nilotinib free base and copovidone. The particulate ASD is admixed with ascorbic acid in a defined weight ratio relative to the nilotinib content, and nilotinib is present in an amount of about 20% w/w to about 30% w/w of the particulate ASD.
The particulate ASD and ascorbic acid admixture are used to improve dissolution and suppress formation of Nilotinib Impurity A during storage. The ascorbic acid is present in an amount of about 0.5 to about 5 times the amount of nilotinib (weight to weight), and storage-related impurity performance includes impurity A limits in ppm.
Pharmaceutical compositions include the particulate ASD of nilotinib free base and copovidone with ascorbic acid, optionally with other pharmaceutically acceptable excipients, and are formulated for oral immediate release use. Particulate ASD physical properties such as particle size distribution and bulk/tapped density are specified, and immediate-release compositions are described with Nilotinib Impurity A acceptance limits.
Claims Coverage
The input explicitly provides one independent claim, directed to a composition comprising a particulate nilotinib free base ASD with copovidone and ascorbic acid in defined weight ratios. Dependent refinements add particulate physical-property constraints, impurity limits, immediate-release composition definitions, and pharmaceutically acceptable excipients.
Particulate nilotinib free base ASD with copovidone and ascorbic acid admixture
A composition comprising a particulate amorphous solid dispersion (ASD) comprising nilotinib free base and copovidone, and ascorbic acid in admixture with the particulate ASD, wherein nilotinib is present in an amount of from about 20% w/w to about 30% w/w of the particulate ASD, and wherein ascorbic acid is present in an amount of from about 0.5 to about 5 times the amount of nilotinib (weight to weight).
Coverage is centered on the particulate nilotinib free base ASD with copovidone combined with ascorbic acid at specified weight ratios, with dependent refinements for particulate physical properties, impurity A limits, immediate-release compositions, and excipient selection.
Stated Advantages
Improves dissolution.
Suppresses formation of Nilotinib Impurity A during storage.
Provides comparable pharmacokinetic exposure versus Tasigna®.
Reduces inter-/intra-subject pharmacokinetic variability.
Mitigates food and gastric-acid interaction concerns.
Documented Applications
Oral immediate-release pharmaceutical compositions comprising the particulate nilotinib/copolyvidone ASD admixed with ascorbic acid.
Treatment of adults with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase, or adults with chronic phase or accelerated phase Philadelphia chromosome positive chronic myeloid leukemia resistant to or intolerant of prior imatinib therapy.
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