Patent application EP16460027A (EP), filed 2016-05-13
Publication number: EP3243505A1
Title: A PHARMACEUTICAL COMPOSITION COMPRISING AMORPHOUS APIXABAN
Abstract: The present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of apixaban or a salt thereof together with one or more pharmaceutically acceptable excipients or carriers, wherein apixaban is amorphous and the composition exhibits an in vitro dissolution profile measured in phosphate buffer at pH 6.8 containing 0.05 % weight/volume of sodium lauryl sulfate according to which: at least 30% of apixaban is dissolved after 5 minutes and at least 60% of apixaban is dissolved after 10 minutes; processes for its preparation and its use for the treatment of thromboembolic diseases or disorders.
IPC codes: A61K   9/    14            A I
A61K   9/    16            A I
A61K   9/    20            A I
Claims: number: 1
text: A pharmaceutical composition comprising a therapeutically effective amount of apixaban or a salt thereof together with one or more pharmaceutically acceptable excipients or carriers, wherein apixaban is amorphous and the composition exhibits an in vitro dissolution profile measured in phosphate buffer at pH 6.8 containing 0.05% weight/volume of sodium lauryl sulfate according to which:
number: 2
text: The composition according to claim 1, wherein the composition exhibits an in vitro dissolution profile measured in phosphate buffer at pH 6.8 containing 0.05% weight/volume of sodium lauryl sulfate according to which:
number: 3
text: The composition according to any of the claims 1-2, wherein the composition is a wet granulation tablet or a hot-melt extruded tablet.
number: 4
text: The composition according to claim 3, wherein the composition is a wet granulation tablet and comprises:
number: 5
text: The composition according to claim 3, wherein the composition is a hot-melt extruded tablet and comprises:
number: 6
text: The composition as defined in any of the claims 4-5, wherein the filler is lactose monohydrate.
number: 7
text: A process for the preparation of a composition as defined in any of the claims 1-4 and 6, which comprises:
number: 8
text: The process according to claim 7, wherein step (i) of the process is performed by heating a mixture of C<1> -C<4> ketone, C<1> -C<4> alcohol, and water, being C<1> -C<4> ketone acetone, C<1> -C<4> alcohol isopropanol and being the weight ratio between C<1> -C<4> ketone, C<1> -C<4> alcohol and water of 1:1:1.
number: 9
text: The process according to any of the claims 7-8, wherein the concentration of apixaban in the granulation dispersion is from 1% to 5%.
number: 10
text: The process according to any of the claims 7-9, further comprises additional steps (c)-(f) after step (b):
number: 11
text: A process for the preparation of a composition as defined in any of the claims 1-3, 5 and 6 which comprises:
number: 12
text: The process according to claim 11, wherein the hot-melt extrudable polymer is a vinylpyrrolidone-vinyl acetate copolymer and the hot-melt extrudable plasticizer is polyethylene glycol, or alternatively the hot-melt extrudable polymer is a vinylpyrrolidone-vinyl acetate copolymer and the hot-melt extrudable plasticizer is polyethylene oxide-polypropylen oxide copolymer.
number: 13
text: The process according to any of the claims 11-12, wherein step (ii) is performed at a melting temperature from 140°C to 240°C and at a feeding rate from 0.05 kg/h to 1.5 kg/h.
number: 14
text: The process according to claim 13, wherein the feeding temperature is from 15°C to 50°C and the pressure at the end of the die is from 0.5 bar to 2 bars.
number: 15
text: A pharmaceutical composition as defined in any of the claims 1-6, for use in the treatment of a venous thromboembolic disease or disorder.
Office action: search_report, dated 2017-11-15
Rejection reasons: novelty_epc_54
Prior art cited: ref_id: US6967208B2
ref_type: patent
severity: background
ref_id: WO2011106478A2
ref_type: patent
severity: background
ref_id: WO2015121472A1
ref_type: patent
severity: background
ref_id: US2007026082A1
ref_type: patent
severity: background
ref_id: WO2015121472A1
ref_type: patent
severity: background
ref_id: WO2011106478A2
ref_type: patent
severity: background
ref_id: EP2554159A1
ref_type: patent
severity: background
ref_id: CN104490834A
ref_type: patent
severity: background
ref_id: CN102908324A
ref_type: patent
severity: background
ref_id: - "Amorphous Formulations of Apixaban by Hot Melt Extrusion", RESEARCH DISCLOSURE, MASON PUBLICATIONS, HAMPSHIRE, GB, vol. 605, no. 34, 1 September 2014 (2014-09-01), pages 5, XP007143402, ISSN: 0374-4353
ref_type: npl
severity: background
ref_id: WO2011106478
ref_type: patent
severity: novelty_destroying
ref_id: EP2554159
ref_type: patent
severity: novelty_destroying
ref_id: CN102908324
ref_type: patent
severity: novelty_destroying
ref_id: CN104490834
ref_type: patent
severity: novelty_destroying
ref_id: - "Amorphous Formulations of Apixaban by Hot Melt Extrusion", RESEARCH DISCLOSURE, MASON PUBLICATIONS, HAMPSHIRE, GB, (20140901), vol. 605, no. 34, ISSN 0374-4353, page 5, XP007143402 [X] 1-3,5,6,11 * tables 1, 4 * [I] 12-14
ref_type: npl
severity: novelty_destroying
Final disposition: pending (2017-11-15)