USOO8383152B2 (12) United States Patent (10) Patent No.: US 8,383,152 B2 Jans et al. (45) Date of Patent: Feb. 26, 2013 (54) PHARMACEUTICAL DOSAGE FORM (58) Field of Classification Search .................. 424/468, 424/464, 474: 514/654 (75) Inventors: Eugeen Marie Jozef Jans, Meerhout See application file for complete search history. (BE); Filip René Irena Kiekens, Geel (BE); Jody Firmin Marceline (56) References Cited Voorspoels, Reningelst (BE); Anne U.S. PATENT DOCUMENTS Faure, Vosselaar (BE); Elisabeth 3,806,603 A 4, 1974 Gaunt et al. Arkenau-Maric, Köln (DE); Lutz 3,865,108 A 2/1975 Hartop Barnscheid, Mönchengladbach (DE); 3,966,747 A 6, 1976 Monkovic et al. Johannes Bartholomäus, Aachen (DE); 3,980,766 A 9, 1976 Shaw et al. 4,002,173 A 1/1977 Manning et al. Marc Frevel, Monschau (DE); Eric 4,014,965 A 3, 1977 Stube et al. Galia, Inden (DE); Iris Ziegler, Neusaf 4,070,494 A 1/1978 Hoffmeister et al. (DE); Andrea Schissele, Berlin (DE) (Continued) (73) Assignee: Gruenenthal GmbH, Anchen (DE) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this AR 46994 12, 2004 patent is extended or adjusted under 35 AR O45.353 10/2005 U.S.C. 154(b) by 368 days. (Continued) (21) Appl. No.: 12/358,415 OTHER PUBLICATIONS El-Egakey, Adeletal, Pharmacerutica Acta Helvetiae, vol. 46, Mar. (22) Filed: Jan. 23, 2009 19, 1970. (65) Prior Publication Data (Continued) US 2009/0202634 A1 Aug. 13, 2009 Primary Examiner — Aradhana Sasan (74) Attorney, Agent, or Firm — Norris McLaughlin & (30) Foreign Application Priority Data Marcus, P.A. Jan. 25, 2008 (EP) ..................................... O8OO1415 (57) ABSTRACT Jan. 25, 2008 (EP). ... O8OO1416 The invention relates to a pharmaceutical dosage form, pref Oct. 17, 2008 (EP) ..................................... O8O18221 erably with controlled release of a pharmacologically active (51) Int. Cl. compound (A) contained therein, the pharmaceutical dosage A6 IK 9/22 (2006.01) form very preferably being tamper-resistant and most prefer A6 IK9/20 (2006.01) ably having a breaking strength B of at least 500 N in direc A6 IK 9/28 (2006.01) tion of extension E and having a breaking strength B of less A6 IK3I/35 (2006.01) than 500 N in direction of extension E. (52) U.S. Cl. ......... 424/468; 424/464; 424/474: 514/654 79 Claims, 21 Drawing Sheets AV6 8 26 A/6 US 8,383,152 B2 Page 2 U.S. PATENT DOCUMENTS 6,238,697 B1 5/2001 Kumar et al. 6,245,357 B1 6/2001 Edgren et al. 1991, A Es Sir et al. 6,248,737 B1 6/2001 Snet al. 4.200,704 A 4/1980 Stanley et al. 3864- W R 658 rabowskihis ki et al. 4,207,893 A 6/1980 Michaels 6,306.438 B1 10/2001 Oshlack et al. 4.262,017 A 4/1981 Kuipers 6,309.668 B1 10/2001 Bastin et al. 4,343,789 A 8/1982 Kawata et al. 6,318,650 B1 1 1/2001 Breitenbach et al. 4,353,887. A 10/1982 Hess et al. 6,340.475 B2 1/2002 Shell et al. is: A 3. SR a 6,344,535 B1 2/2002 Timmermann et al. 4.462,941. A 7/1984 Lee et al. g:- - - R 53. 5.eitlin et al. 2.E. A 38. Sch 1 6,375,957 B1 4/2002 Kaiko et al. 4.62963. A 13/1986 SE a. 6,375,963 B1 4/2002 Repka et al. 4,667,013 A 5/1987 Reichle s R $39: lay s al. 4,690,822. A 9, 1987 Uemura et al. 6.436.441 B1 8/2002 SE 4,713,243 A 12/1987 Schiraldi et al. 6,461.644 B1 102002 Jackson etal 4,744.976 A 5/1988 Snipes et al. 6,488.939I wr. B1 12/2002 Zeidler et al. 3. A 3. St. et al 6,488.962 B1 12/2002 Berner et al. 4.774,074 A 9, 1988 Set al. 6,488.963 B1 12/2002 McGinity et al. pe 6,534,089 B1 3/2003 Ayer et al. 2592 A 28. SE" 6,547.997 B1 4/2003 Breithenbach et al. 4,806,337 A 2/1989 Snipes et al. 8360 R 39. E. RE33,093 E 10/1989 Schiraldi et al. 6,592.90 B2 7/2003 Duriget al. 4,880,585 A 11, 1989 Klimesch et al. 6,635,280 B2 10, 2003 Shell et al. 4,892.889.4,892.778 A 1/1990 TheeuwesKirk et al. 6,699,503w - - B1 3/2004 Sako et al. 4,940,556 A 7/1990 MacFarlane et al. 22, R: 2. SA 4,957,668 A 9/1990 Plackard et al. 6.733,783 B2 5/2004 Oshacketal 4,957,681 A 9, 1990 Klimesch et al. 6.753.009 B2 6/2004 Luber et al. 4,960,814. A 10/1990 Wu et al. 6,821,588 B1 1 1/2004 Hammer 4,992.278 A 2/1991 Khanna 7,074,430 B2 7/2006 Miller et al. 4992,279 A 2, 1991 Palmer et al. 7,129,248 B2 10/2006 Chapman et al. 5,004,601. A 4, 1991 Snipes 7,141,250 B2 11/2006 Oshlack et al. 3. A 992, Minist al. 7,157,103 B2 1/2007 Sackler 5,139,790 A 8, 1992 Stal 7,176,251 B1 2/2007 Bastioli et al. 5,169,645 A 12/1992 Shukla et al. 239, R: $39, Set al. 5, 198,226 A 3/1993 MacFarlane et al. 7.300.668 B2 11/2007 Prvce Lewis etal 5,200,1974. WW A 4/1993 Wright et al. 7,399,488- WW B2 7/2008 Hirshy et al. 5,211,892 A 5/1993 Gueret 7,674,799 B2 3/2010 Chapman et al. 357 A 392. Ri, 7,674,800 B2 3/2010 Chapman et al. 5,378.462- - W A 1/1995 Boedecker et al. 7637,683,072 (4.5 B2 3/2010s 568 ChapmanAAct et al. al. RES f $32 kNE a 7,851.482 B2 12/2010 Dung et al. 5,458.887. A 10, 1995 Chen et al. 7,939,543$65,875 B2 3.5G5/2011 KupperARGu-Marie et al. is: A 1998 SE i 8,114,383 B2 2/2012 Bartholomaus et al. 5,556.640 A 9, 1996 his et al. 8, 192,722 B2 6/2012 Arkenau-Maric et al. 5.562920 A * 10, 1996 Demmer et al. ... 424/464 2001/0038852 A1 11/2001 Kolter et al. - W4- 2002/0012701 A1 1/2002 Kolter et al. 5,593,694. A 1/1997 Hayashida et al. 2002fOO15730 A1 2/2002 Hoffmann et al. 5,601,842 A 2, 1997 Bartholomaeus 2002/0051820 A1 5, 2002. Shell et al. E.g. A 1887 St. et al. 2002/01 14838 A1 8/2002 Ayer et al. wwk 2002/0132359 A1 9, 2002 Waterman 3.- 4 A SE E. et al. 2002fO1871.922002/0176888 A1Al 12/200211/2002 JoshiBartholomaeus et al. et al. 349; A 3.32. EN Sh 2002/0192277 A1 12/2002 Oshacket al. 5,849,340 A 12/1998 East y 2003/0008409 A1 1/2003 Spearman et al. w I-1 2003, OO15814 A1 1/2003 Krull et al. 38885 A &E Syst al. 2003/0017532 A1 1/2003 Biswas et al. 5,916,584 A 6/1999 O’Donoghue et al. 38: A. 58. A. tal 5,928.739-- aw A 7/1999 Pophusen et al. 2003/0044458 A1 3/2003 WrightKi et et al. al. 3.292 A 1992 grabowski et al. 2003/0044464 A1 3/2003 Zeigler et al. 5.948.787 A 9, 1999 Sin etal 2003/0064.099 A1 4/2003 Oshlack et al. 5.968935 A 10, 1999 Knidiberge 2003/0068276 A1 4/2003 Hughes et al. 6001391. A 13/1999 E. 2003.0068370 A1 4, 2003 Sackler 60093.90 A 2, 1999 Gupta et al. 2003/0068371 A1 4/2003 Oshlack et al. 6,009,690 1/2000 Rosenberg et al. 2003.0068392 A1 4/2003 Sackler 6,096,339 A 8/2000 Ayer et al. 2003/0091630 A1 5/2003 Louie-Helmet al. 6,117,453 A 9, 2000 Seth et al. 2003. O104052 A1 6/2003 Berner et al. 6,120,802 A 9, 2000 Breitenbach et al. 2003. O104053 A1 6/2003 Gusler et al. 6,133,241. A 10/2000 Bok et al. 2003/01 18641 A1 6/2003 Maloney et al. 6,228,863 B1 5/2001 Palermo et al. 2003/O1241.85 A1 7/2003 Oshlack et al. 6,235,825 B1 5/2001 Yoshida et al. 2003/O125347 A1 7/2003 Anderson et al. US 8,383,152 B2 Page 3 2003/033985 A1 7/2003 Louie-Helmet al. 2010, 0221322 A1 9/2010 Bartholomaus et al. 2003/0152622 A1 8/2003 Louie-Helmet al. 2010/0226855 A1 9/2010 Nangia et al. 2003/0158242 A1 8/2003 Kugelmann 2010/0249045 A1 9, 2010 Babul 2003/0175326 A1 9, 2003 Thombre 2010.0260833 A1 10, 2010 Bartholomaus et al. 2003/0232895 A1 12/2003 Omidian et al. 2011/0020451 A1 1/2011 Bartholomaus et al. 2004/0010000 A1 1/2004 Ayer et al. 2011/0020454 A1 1/2011 Casado 2004/0011806 A1 1/2004 Luciano et al. 2011/003893.0 A1 2/2011 Barnscheid et al. 2004/0052731 A1 3, 2004 Hirsh et al. 2011/0082214 A1 4/2011 Faure et al. 2004/0052844 A1 3f2004 Hsiao et al.