Patent application EP16174466A (EP), filed 2016-06-14
Publication number: EP3257501A1
Title: MULTIPLE UNIT DOSAGE FORM COMPRISING A CORE WITH INDIVIDUAL CORE UNITS COVERED BY A MUCOADHESIVE MATERIAL, AND AN ENTERIC CORE COATING
Abstract: The present invention relates to a multiple unit dosage form comprising a core, wherein the core comprises a plurality of individual units, each unit comprising a pharmaceutically active ingredient and each unit being covered with a mucoadhesive material, and wherein the multiple unit dosage form further comprises an enteric core coating layer. The invention furthermore relates to the use of said multiple unit dosage form in the treatment of inflammatory disorders, especially for the gastrointestinal tract.
IPC codes: A61K  31/  4164            A I
A61K   9/    48            A I
A61K   9/    50            A I
A61P   1/    00            A I
Claims: number: 1
text: A multiple unit dosage form comprising
number: 2
text: The multiple unit dosage form according to claim 1, wherein the core coating (b) comprises a further coating layer (b2),
wherein said further coating layer (b2) is between the core (a) and the outer coating layer (b1), and wherein said further coating layer (b2) comprises a polymeric material which is soluble in intestinal fluid or gastric fluid and which is selected from the group consisting of a polycarboxylic acid polymer that is at least partially neutralized and a non-ionic polymer, each in combination with at least one additive selected from a buffer agent and/or a base and mixtures thereof.
number: 3
text: The multiple unit dosage form according to claim 2, wherein the further coating layer (b2) of the core coating (b) is an alkaline layer, which means that the layer material when dissolved in 10 times its weight of water provides a pH value above the pH threshold at which the enteric polymer in the outer coating (b1) dissolves.
number: 4
text: The multiple unit dosage form according to any of the preceding claims, wherein the at least one mucoadhesive material (a2) comprises chitosan or alginate, preferably chitosan.
number: 5
text: The multiple unit dosage form according to any of the preceding claims, wherein the at least one mucoadhesive material (a2) is present in a mucoadhesive controlled release coating layer covering the individual units, wherein the active ingredient is released over a time period of at least 30 minutes in simulated intestinal fluid when tested under the following conditions:
number: 6
text: The multiple unit dosage form according to any of the preceding claims, wherein the outer coating layer (b1) of core coating (b) which is an enteric coating layer comprises a polymeric material which has a pH threshold of about pH 5 or above, i.e. which dissolves at a pH threshold of about pH 5 or above and is insoluble at more acidic pH values.
number: 7
text: The multiple unit dosage form according to claim 6, wherein the outer coating layer (b1) which is an enteric coating of core coating (b) also comprises a polymeric material which is susceptible to an attack by colonic bacteria.
number: 8
text: A multiple unit dosage form according to any of the preceding claims, wherein the individual units are selected from porous microparticles, granules, pellets and mini tablets, preferably pellets.
number: 9
text: The multiple unit dosage form according any of the preceding claims, wherein each individual unit has a maximum outer diameter in the range of 100 µm to 1 mm, preferably in the range of 100 µm to 500 µm.
number: 10
text: The multiple unit dosage form according to any of the preceding claims, wherein the core is a tablet or a hard-shell capsule, preferably a hard-shell capsule.
number: 11
text: The multiple unit dosage form according to any of the preceding claims, wherein the pharmaceutically active ingredient (a1) is an anti-inflammatory agent or antibiotic.
number: 12
text: The multiple unit dosage form according to any of claims 1 to 11, wherein the pharmaceutically active ingredient (a1) is selected from metronidazole, vancomycine, 5-amino-salicylic acid, budesonide, and anti-TNFs, and is preferably metronidazole.
number: 13
text: The multiple unit dosage form according to any of the preceding claims, wherein the individual units of core (a) comprise an inert seed core onto which a first coating layer is coated containing the pharmaceutically active ingredient (a1) onto which a mucoadhesive coating layer comprising the mucoadhesive material (a2) is coated.
number: 14
text: The multiple unit dosage form according to claim 13, wherein the seed core comprises, preferably consists of functionalized calcium carbonate (FCC) as porous drug carrier.
number: 15
text: The multiple unit dosage form according to any of the preceding claims for use in the treatment of inflammatory disorders.
number: 16
text: The multiple unit dosage form according to claim 15 for use in the treatment of inflammatory bowel diseases wherein the inflammatory bowel disease is preferably selected from Crohn's disease, ulcerative colitis and other kinds of colitis including.
Office action: search_report, dated 2017-12-20
Rejection reasons: novelty_epc_54
inventive_step_epc_56
Prior art cited: ref_id: US4627851A
ref_type: patent
severity: background
ref_id: WO8300435A1
ref_type: patent
severity: background
ref_id: WO2007122374A2
ref_type: patent
severity: background
ref_id: EP2018159A2
ref_type: patent
severity: background
ref_id: WO2008135090A1
ref_type: patent
severity: background
ref_id: WO2013164315A1
ref_type: patent
severity: background
ref_id: WO2013164316A1
ref_type: patent
severity: background
ref_id: WO2015062640A1
ref_type: patent
severity: background
ref_id: EP2264108A1
ref_type: patent
severity: background
ref_id: WO2010037753A1
ref_type: patent
severity: background
ref_id: - LAMPRECHT ET AL., EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, vol. 81, 2012, pages 379 - 385
ref_type: npl
severity: background
ref_id: - JOURNAL OF PHARMACY AND PHARMACOLOGY, vol. 59, 2007, pages 209 - 223
ref_type: npl
severity: background
ref_id: WO2009138716A1
ref_type: patent
severity: background
ref_id: WO2015062640A1
ref_type: patent
severity: background
ref_id: - DATABASE EMBASE [online] ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL; January 2011 (2011-01-01), SIVAKUMAR R ET AL: "Design of mucoadhesive hydropilic beads entrapped with ketoprofen for delivery into small intestine", XP002765200, Database accession no. EMB-2011122327
ref_type: npl
severity: background
ref_id: - RESEARCH JOURNAL OF PHARMACEUTICAL, BIOLOGICAL AND CHEMICAL SCIENCES 2011 RESEARCH JOURNAL OF PHARMACEUTICAL, BIOLOGICAL AND CHEMICAL IND, vol. 2, no. 1, January 2011 (2011-01-01), pages 706 - 713, ISSN: 0975-8585
ref_type: npl
severity: background
ref_id: - ASGHAR L F A ET AL: "Multiparticulate formulation to colon specific drug delivery: current perspectives", JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, CANADIAN SOCIETY FOR PHARMACEUTICAL SCIENCES, EDMONTON, CA, vol. 9, no. 3, 16 November 2006 (2006-11-16), pages 327 - 338, XP002473928, ISSN: 1482-1826, [retrieved on 20061116]
ref_type: npl
severity: background
ref_id: - TEREZA BAUTZOVÁ ET AL: "Bioadhesive pellets increase local 5-aminosalicylic acid concentration in experimental colitis", EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS., vol. 81, no. 2, 1 June 2012 (2012-06-01), NL, pages 379 - 385, XP055329108, ISSN: 0939-6411, DOI: 10.1016/j.ejpb.2012.02.011
ref_type: npl
severity: background
ref_id: WO2009138716
ref_type: patent
severity: novelty_destroying
ref_id: WO2015062640
ref_type: patent
severity: obviousness
ref_id: - SIVAKUMAR R ET AL, "Design of mucoadhesive hydropilic beads entrapped with ketoprofen for delivery into small intestine", EMBASE, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, (201101), Database accession no. EMB-2011122327, XP002765200 [X] 1-16 * abstract *
ref_type: npl
severity: novelty_destroying
ref_id: [ ]     - RESEARCH JOURNAL OF PHARMACEUTICAL, BIOLOGICAL AND CHEMICAL SCIENCES 2011 RESEARCH JOURNAL OF PHARMACEUTICAL, BIOLOGICAL AND CHEMICAL IND, (201101), vol. 2, no. 1, ISSN 0975-8585, pages 706 - 713
ref_type: npl
severity: background
ref_id: - ASGHAR L F A ET AL, "Multiparticulate formulation to colon specific drug delivery: current perspectives", JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, CANADIAN SOCIETY FOR PHARMACEUTICAL SCIENCES, EDMONTON, CA, vol. 9, no. 3, ISSN 1482-1826, (20061116), pages 327 - 338, (20061116), XP002473928 [X] 1-16 * the whole document * * in particular page 330, right column, first full paragraph *
ref_type: npl
severity: novelty_destroying
ref_id: - TEREZA BAUTZOVÁ ET AL, "Bioadhesive pellets increase local 5-aminosalicylic acid concentration in experimental colitis", EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS., NL, (20120601), vol. 81, no. 2, doi:10.1016/j.ejpb.2012.02.011, ISSN 0939-6411, pages 379 - 385, XP055329108 [YD] 1-16 * the whole document *
ref_type: npl
severity: obviousness
Final disposition: pending (2017-12-20)