Patent application EP16163916A (EP), filed 2016-04-05
Publication number: EP3228307A1
Title: SOLID DISPERSION COMPRISING OPIOID ANTAGONISTS
Abstract: The present invention relates to a solid dispersion comprising, preferably consisting of, naloxegol salts in amorphous form and at least one pharmaceutically acceptable matrix compound and wherein the matrix compound is (i) an organic polymer, or (ii) a silicon-based inorganic adsorbent.  Further, the present invention also relates to a process for preparing a solid dispersion comprising naloxegol in amorphous form and at least one pharmaceutically acceptable matrix compound, as well as to a solid dispersion obtained or obtainable by said process. Further, the present invention relates to a pharmaceutical composition comprising such solid dispersion as well as a pharmaceutical composition for use as µ-opioid antagonists.
IPC codes: A61K   9/    10            A I
Claims: number: 1
text: A solid dispersion comprising a naloxegol salt [(5α,6α)-17-allyl-6-(2,5,8,11,14,17,20-heptaoxadocosan-22-yloxy)-4,5-epoxymorphinan-3,14-diol] in amorphous form and at least one pharmaceutically acceptable solid matrix compound.
number: 2
text: The solid dispersion according to claim 1, wherein the at least one matrix compound is
number: 3
text: The solid dispersion according to claim 1 or 2, wherein at least 80 % by weight of the naloxegol salt present in the solid dispersion is in amorphous form.
number: 4
text: The solid dispersion according to any one of claims 1 to 3, wherein the naloxegol salt is a salt of naloxegol with an organic acid.
number: 5
text: The solid dispersion according to any one of the claims 1 to 4 wherein the organic acid is selected from the group comprising tartaric acid and 1,2-ethanedisulfonic acid.
number: 6
text: The solid dispersion according to claim 5, wherein the naloxegol salt is a hemi-1,2-ethanedisulfonate salt.
number: 7
text: The solid dispersion according to claim 5, wherein the naloxegol salt is a D-tartrate salt.
number: 8
text: The solid dispersion according to any one of the claims 1 to 7, wherein the polymer (i) is a cellulose derivative or a polyvinyl caprolactam polyvinyl acetate polyethylene glycol graft polymer.
number: 9
text: The solid dispersion according to claim 8, wherein the cellulose derivative is a hydroxyalkylalkylcellulose or a mixture of two or more hydroxyalkylalkylcelluloses.
number: 10
text: The solid dispersion according to any one of the claims 8 and 9, wherein the hydroxyalkylalkylcellulose is HPMC-AS.
number: 11
text: A process for the preparation of a solid dispersion comprising a naloxegol salt in amorphous form and at least one pharmaceutical acceptable matrix compound, the process comprising
number: 12
text: The solid dispersion obtained or obtainable by the process according to claim 11.
number: 13
text: The pharmaceutical composition according to any one of claims 1 to 12 for the treatment of opiod-induced bowel dysfunction.
number: 14
text: Use of a pharmaceutically acceptable solid matrix compound for isolating a salt of an active pharmaceutical ingredient as a flowable powder, wherein said salt of said active pharmaceutical ingredient by itself cannot be isolated as a flowable powder at room temperature and at 50% relative humidity.
number: 15
text: Use of a pharmaceutically acceptable solid matrix compound for the preparation of a free-flowing powder comprising a salt of an active pharmaceutical ingredient in a solid state, wherein said salt of said active pharmaceutical ingredient by itself cannot be prepared as a free-flowing powder at room temperature and at 50% relative humidity, preferably wherein said salt of an active pharmaceutical ingredient by itself cannot be isolated as a solid at room temperature and at 50% relative humidity.
Office action: search_report, dated 2017-10-11
Rejection reasons: novelty_epc_54
inventive_step_epc_56
Prior art cited: ref_id: WO2005058367A2
ref_type: patent
severity: background
ref_id: WO2008057579A2
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severity: background
ref_id: WO2012044243A1
ref_type: patent
severity: background
ref_id: US2003163931A1
ref_type: patent
severity: background
ref_id: - WEBSTER ET AL.: "NKTR-118 Significantly Reverses Opioid-Induced-Constipation", 20TH AAPM ANNUAL CLINICAL MEETING (PHOENIX, AZ, 10 October 2009 (2009-10-10)
ref_type: npl
severity: background
ref_id: - MADRONERO ET AL: "Synthesis and study of new ganglioplegic agents", ANALES DE LA REAL ACADEMIA DE FARMACIA,, vol. 34, no. 2, 1 January 1968 (1968-01-01), pages 173 - 195, XP009190419, ISSN: 0034-0618
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severity: background
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severity: background
ref_id: - A. KAVANAGH: "Developing Amorphous Pharmaceuticals: Opportunity and Necessity", AMERICAN PHARMACEUTICAL REVIEW - THE REVIEW OF AMERICAN PHARMACEUTICAL BUSINESS & TECHNOLOGY, 21 August 2012 (2012-08-21), pages 1 - 7, XP055157921, Retrieved from the Internet <URL:http://www.americanpharmaceuticalreview.com/Featured-Articles/119521-Developing-Amorphous-Pharmaceuticals-Opportunity-and-Necessity/> [retrieved on 20141211]
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severity: background
ref_id: - K NAGAPUDI ET AL: "Amorphous Active Pharmaceutical Ingredients in Preclinical Studies: Preparation, Characterization, and Formulation", CURRENT BIOACTIVE COMPOUNDS, vol. 4, 1 December 2008 (2008-12-01), pages 213 - 224, XP055078333
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severity: background
ref_id: - DATABASE PubChem Compound [online] 24 September 2012 (2012-09-24), XP002762374, retrieved from NCBI Database accession no. 18391755
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severity: background
ref_id: - DATABASE PubChem Compound [online] 24 June 2005 (2005-06-24), XP002762375, retrieved from NCBI Database accession no. 443968
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severity: background
ref_id: - DATABASE PubChem Compound [online] 25 October 2006 (2006-10-25), XP002762376, retrieved from NCBI Database accession no. 9936934
ref_type: npl
severity: background
ref_id: US3247064
ref_type: patent
severity: novelty_destroying
ref_id: US4603143
ref_type: patent
severity: obviousness
ref_id: US2007082919
ref_type: patent
severity: obviousness
ref_id: WO2008043701
ref_type: patent
severity: background
ref_id: WO2012044243
ref_type: patent
severity: obviousness
ref_id: WO2013130766
ref_type: patent
severity: novelty_destroying
ref_id: - A. Kavanagh, "Developing Amorphous Pharmaceuticals: Opportunity and Necessity", American Pharmaceutical Review - The Review of American Pharmaceutical Business & Technology, (20120821), pages 1 - 7, URL: http://www.americanpharmaceuticalreview.com/Featured-Articles/119521-Developing-Amorphous-Pharmaceuticals-Opportunity-and-Necessity/, (20141211), XP055157921 [Y] 1-15 * pages  1,4,5 *
ref_type: npl
severity: obviousness
ref_id: - K NAGAPUDI ET AL, "Amorphous Active Pharmaceutical Ingredients in Preclinical Studies: Preparation, Characterization, and Formulation", CURRENT BIOACTIVE COMPOUNDS, (20081201), vol. 4, pages 213 - 224, XP055078333 [Y] 1-15 * paragraphs  [0002] , [ 5.1] *
ref_type: npl
severity: obviousness
ref_id: - PubChem Compound, (20120924), Database accession no. 18391755, URL: NCBI, XP002762374 [Y] 14,15 * compound 18391755 *
ref_type: npl
severity: obviousness
ref_id: - PubChem Compound, (20050624), Database accession no. 443968, URL: NCBI, XP002762375 [Y] 14,15 * compound 443968 *
ref_type: npl
severity: obviousness
ref_id: - PubChem Compound, (20061025), Database accession no. 9936934, URL: NCBI, XP002762376 [Y] 14,15 * compound 9936934 *
ref_type: npl
severity: obviousness
Final disposition: pending (2017-10-11)