CA2690829A1 - Formulations d'analgesiques non opioides et d'analgesiques opioides captifs - Google Patents

Formulations d'analgesiques non opioides et d'analgesiques opioides captifs Download PDF

Info

Publication number: CA2690829A1
Authority: CA; Canada
Prior art keywords: hours; composition; acetaminophen; hydrocodone; released
Prior art date: 2007-07-20
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA2690829A

Other languages

English (en)

Inventor

Joerg Rosenberg

Gerd Woehrle

Thomas Y. Kessler

Joerg Breitenbach

Salih Durak

Friedrich W. Richter

Sandeep Dutta

Wei Liu

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

AbbVie Deutschland GmbH and Co KG

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2007-07-20

Filing date

2007-07-20

Publication date

2009-01-29

2007-07-20 Application filed by Individual filed Critical Individual

2009-01-29 Publication of CA2690829A1 publication Critical patent/CA2690829A1/fr

Status Abandoned legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 453
238000009472 formulation Methods 0.000 title claims abstract description 184
229940005483 opioid analgesics Drugs 0.000 title description 8
239000000014 opioid analgesic Substances 0.000 title description 4
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 906
229960005489 paracetamol Drugs 0.000 claims abstract description 453
XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 claims abstract description 310
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims abstract description 310
LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 claims abstract description 309
229960000240 hydrocodone Drugs 0.000 claims abstract description 308
LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 claims abstract description 306
239000003814 drug Substances 0.000 claims abstract description 254
229940079593 drug Drugs 0.000 claims abstract description 253
239000002552 dosage form Substances 0.000 claims abstract description 92
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 20
229960001680 ibuprofen Drugs 0.000 claims abstract description 20
238000000227 grinding Methods 0.000 claims abstract description 15
239000008194 pharmaceutical composition Substances 0.000 claims description 292
238000000338 in vitro Methods 0.000 claims description 186
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 105
239000012792 core layer Substances 0.000 claims description 98
VDPLLINNMXFNQX-UHFFFAOYSA-N (1-aminocyclohexyl)methanol Chemical compound OCC1(N)CCCCC1 VDPLLINNMXFNQX-UHFFFAOYSA-N 0.000 claims description 77
229960002764 hydrocodone bitartrate Drugs 0.000 claims description 77
229920000642 polymer Polymers 0.000 claims description 74
238000004090 dissolution Methods 0.000 claims description 72
238000012360 testing method Methods 0.000 claims description 65
-1 nalbulphine Chemical compound 0.000 claims description 52
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 50
229920001577 copolymer Polymers 0.000 claims description 48
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 39
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 39
239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 37
229940121367 non-opioid analgesics Drugs 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 30
229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 26
238000001125 extrusion Methods 0.000 claims description 22
239000007921 spray Substances 0.000 claims description 21
239000000546 pharmaceutical excipient Substances 0.000 claims description 19
230000002051 biphasic effect Effects 0.000 claims description 17
238000007493 shaping process Methods 0.000 claims description 17
239000004372 Polyvinyl alcohol Substances 0.000 claims description 16
229920002451 polyvinyl alcohol Polymers 0.000 claims description 16
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 15
238000009506 drug dissolution testing Methods 0.000 claims description 12
238000001727 in vivo Methods 0.000 claims description 12
229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 9
235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 9
239000001863 hydroxypropyl cellulose Substances 0.000 claims description 9
238000007873 sieving Methods 0.000 claims description 9
DEXMFYZAHXMZNM-UHFFFAOYSA-N Narceine Chemical compound OC(=O)C1=C(OC)C(OC)=CC=C1C(=O)CC1=C(CCN(C)C)C=C(OCO2)C2=C1OC DEXMFYZAHXMZNM-UHFFFAOYSA-N 0.000 claims description 8
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 8
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 8
CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 claims description 8
GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 claims description 8
229920000578 graft copolymer Polymers 0.000 claims description 7
150000004677 hydrates Chemical class 0.000 claims description 6
239000000049 pigment Substances 0.000 claims description 6
229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 5
239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 5
235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 5
229920000193 polymethacrylate Polymers 0.000 claims description 5
YQYVFVRQLZMJKJ-JBBXEZCESA-N (+)-cyclazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CC1CC1 YQYVFVRQLZMJKJ-JBBXEZCESA-N 0.000 claims description 4
WRRSFOZOETZUPG-FFHNEAJVSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;hydrate Chemical compound O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC WRRSFOZOETZUPG-FFHNEAJVSA-N 0.000 claims description 4
TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 claims description 4
USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims description 4
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 4
IJVCSMSMFSCRME-KBQPJGBKSA-N Dihydromorphine Chemical compound O([C@H]1[C@H](CC[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O IJVCSMSMFSCRME-KBQPJGBKSA-N 0.000 claims description 4
OGDVEMNWJVYAJL-LEPYJNQMSA-N Ethyl morphine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OCC OGDVEMNWJVYAJL-LEPYJNQMSA-N 0.000 claims description 4
OGDVEMNWJVYAJL-UHFFFAOYSA-N Ethylmorphine Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OCC OGDVEMNWJVYAJL-UHFFFAOYSA-N 0.000 claims description 4
GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 claims description 4
102000006992 Interferon-alpha Human genes 0.000 claims description 4
108010047761 Interferon-alpha Proteins 0.000 claims description 4
ALFGKMXHOUSVAD-UHFFFAOYSA-N Ketobemidone Chemical compound C=1C=CC(O)=CC=1C1(C(=O)CC)CCN(C)CC1 ALFGKMXHOUSVAD-UHFFFAOYSA-N 0.000 claims description 4
OZYUPQUCAUTOBP-QXAKKESOSA-N Levallorphan Chemical compound C([C@H]12)CCC[C@@]11CCN(CC=C)[C@@H]2CC2=CC=C(O)C=C21 OZYUPQUCAUTOBP-QXAKKESOSA-N 0.000 claims description 4
JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 claims description 4
XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims description 4
IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 claims description 4
CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 4
239000008896 Opium Substances 0.000 claims description 4
BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 claims description 4
UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 claims description 4
229960001138 acetylsalicylic acid Drugs 0.000 claims description 4
229960001391 alfentanil Drugs 0.000 claims description 4
KGYFOSCXVAXULR-UHFFFAOYSA-N allylprodine Chemical compound C=1C=CC=CC=1C1(OC(=O)CC)CCN(C)CC1CC=C KGYFOSCXVAXULR-UHFFFAOYSA-N 0.000 claims description 4
229950004361 allylprodine Drugs 0.000 claims description 4
229960001349 alphaprodine Drugs 0.000 claims description 4
UVAZQQHAVMNMHE-XJKSGUPXSA-N alphaprodine Chemical compound C=1C=CC=CC=1[C@@]1(OC(=O)CC)CCN(C)C[C@@H]1C UVAZQQHAVMNMHE-XJKSGUPXSA-N 0.000 claims description 4
LKYQLAWMNBFNJT-UHFFFAOYSA-N anileridine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC1=CC=C(N)C=C1 LKYQLAWMNBFNJT-UHFFFAOYSA-N 0.000 claims description 4
229960002512 anileridine Drugs 0.000 claims description 4
RDJGWRFTDZZXSM-RNWLQCGYSA-N benzylmorphine Chemical compound O([C@@H]1[C@]23CCN([C@H](C4)[C@@H]3C=C[C@@H]1O)C)C1=C2C4=CC=C1OCC1=CC=CC=C1 RDJGWRFTDZZXSM-RNWLQCGYSA-N 0.000 claims description 4
FLKWNFFCSSJANB-UHFFFAOYSA-N bezitramide Chemical compound O=C1N(C(=O)CC)C2=CC=CC=C2N1C(CC1)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 FLKWNFFCSSJANB-UHFFFAOYSA-N 0.000 claims description 4
229960004611 bezitramide Drugs 0.000 claims description 4
RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims description 4
229960001736 buprenorphine Drugs 0.000 claims description 4
IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 claims description 4
229960001113 butorphanol Drugs 0.000 claims description 4
GPZLDQAEBHTMPG-UHFFFAOYSA-N clonitazene Chemical compound N=1C2=CC([N+]([O-])=O)=CC=C2N(CCN(CC)CC)C=1CC1=CC=C(Cl)C=C1 GPZLDQAEBHTMPG-UHFFFAOYSA-N 0.000 claims description 4
229950001604 clonitazene Drugs 0.000 claims description 4
229960004126 codeine Drugs 0.000 claims description 4
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Natural products C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 4
229950002213 cyclazocine Drugs 0.000 claims description 4
229950003851 desomorphine Drugs 0.000 claims description 4
LNNWVNGFPYWNQE-GMIGKAJZSA-N desomorphine Chemical compound C1C2=CC=C(O)C3=C2[C@]24CCN(C)[C@H]1[C@@H]2CCC[C@@H]4O3 LNNWVNGFPYWNQE-GMIGKAJZSA-N 0.000 claims description 4
WDEFBBTXULIOBB-WBVHZDCISA-N dextilidine Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)OCC)CCC=C[C@H]1N(C)C WDEFBBTXULIOBB-WBVHZDCISA-N 0.000 claims description 4
229960003701 dextromoramide Drugs 0.000 claims description 4
INUNXTSAACVKJS-OAQYLSRUSA-N dextromoramide Chemical compound C([C@@H](C)C(C(=O)N1CCCC1)(C=1C=CC=CC=1)C=1C=CC=CC=1)N1CCOCC1 INUNXTSAACVKJS-OAQYLSRUSA-N 0.000 claims description 4
229960004193 dextropropoxyphene Drugs 0.000 claims description 4
XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 claims description 4
229960003461 dezocine Drugs 0.000 claims description 4
VTMVHDZWSFQSQP-VBNZEHGJSA-N dezocine Chemical compound C1CCCC[C@H]2CC3=CC=C(O)C=C3[C@]1(C)[C@H]2N VTMVHDZWSFQSQP-VBNZEHGJSA-N 0.000 claims description 4
229960002069 diamorphine Drugs 0.000 claims description 4
RXTHKWVSXOIHJS-UHFFFAOYSA-N diampromide Chemical compound C=1C=CC=CC=1N(C(=O)CC)CC(C)N(C)CCC1=CC=CC=C1 RXTHKWVSXOIHJS-UHFFFAOYSA-N 0.000 claims description 4
229950001059 diampromide Drugs 0.000 claims description 4
RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 claims description 4
229960000920 dihydrocodeine Drugs 0.000 claims description 4
RHUWRJWFHUKVED-UHFFFAOYSA-N dimenoxadol Chemical compound C=1C=CC=CC=1C(C(=O)OCCN(C)C)(OCC)C1=CC=CC=C1 RHUWRJWFHUKVED-UHFFFAOYSA-N 0.000 claims description 4
229950011187 dimenoxadol Drugs 0.000 claims description 4
QIRAYNIFEOXSPW-UHFFFAOYSA-N dimepheptanol Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(O)CC)C1=CC=CC=C1 QIRAYNIFEOXSPW-UHFFFAOYSA-N 0.000 claims description 4
229950004655 dimepheptanol Drugs 0.000 claims description 4
CANBGVXYBPOLRR-UHFFFAOYSA-N dimethylthiambutene Chemical compound C=1C=CSC=1C(=CC(C)N(C)C)C1=CC=CS1 CANBGVXYBPOLRR-UHFFFAOYSA-N 0.000 claims description 4
229950005563 dimethylthiambutene Drugs 0.000 claims description 4
229950008972 dioxaphetyl butyrate Drugs 0.000 claims description 4
SVDHSZFEQYXRDC-UHFFFAOYSA-N dipipanone Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)CC)CC(C)N1CCCCC1 SVDHSZFEQYXRDC-UHFFFAOYSA-N 0.000 claims description 4
229960002500 dipipanone Drugs 0.000 claims description 4
ZOWQTJXNFTWSCS-IAQYHMDHSA-N eptazocine Chemical compound C1N(C)CC[C@@]2(C)C3=CC(O)=CC=C3C[C@@H]1C2 ZOWQTJXNFTWSCS-IAQYHMDHSA-N 0.000 claims description 4
229950010920 eptazocine Drugs 0.000 claims description 4
WGJHHMKQBWSQIY-UHFFFAOYSA-N ethoheptazine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCCN(C)CC1 WGJHHMKQBWSQIY-UHFFFAOYSA-N 0.000 claims description 4
229960000569 ethoheptazine Drugs 0.000 claims description 4
MORSAEFGQPDBKM-UHFFFAOYSA-N ethylmethylthiambutene Chemical compound C=1C=CSC=1C(=CC(C)N(C)CC)C1=CC=CS1 MORSAEFGQPDBKM-UHFFFAOYSA-N 0.000 claims description 4
229950006111 ethylmethylthiambutene Drugs 0.000 claims description 4
229960004578 ethylmorphine Drugs 0.000 claims description 4
PXDBZSCGSQSKST-UHFFFAOYSA-N etonitazene Chemical compound C1=CC(OCC)=CC=C1CC1=NC2=CC([N+]([O-])=O)=CC=C2N1CCN(CC)CC PXDBZSCGSQSKST-UHFFFAOYSA-N 0.000 claims description 4
229950004538 etonitazene Drugs 0.000 claims description 4
229960002428 fentanyl Drugs 0.000 claims description 4
WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 claims description 4
229960001410 hydromorphone Drugs 0.000 claims description 4
WTJBNMUWRKPFRS-UHFFFAOYSA-N hydroxypethidine Chemical compound C=1C=CC(O)=CC=1C1(C(=O)OCC)CCN(C)CC1 WTJBNMUWRKPFRS-UHFFFAOYSA-N 0.000 claims description 4
229950008496 hydroxypethidine Drugs 0.000 claims description 4
229960000905 indomethacin Drugs 0.000 claims description 4
IFKPLJWIEQBPGG-UHFFFAOYSA-N isomethadone Chemical compound C=1C=CC=CC=1C(C(C)CN(C)C)(C(=O)CC)C1=CC=CC=C1 IFKPLJWIEQBPGG-UHFFFAOYSA-N 0.000 claims description 4
229950009272 isomethadone Drugs 0.000 claims description 4
229960003029 ketobemidone Drugs 0.000 claims description 4
229960004752 ketorolac Drugs 0.000 claims description 4
OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 claims description 4
229960000263 levallorphan Drugs 0.000 claims description 4
RCYBMSQOSGJZLO-BGWNEDDSSA-N levophenacylmorphan Chemical compound C([C@]12CCCC[C@H]1[C@H]1CC3=CC=C(C=C32)O)CN1CC(=O)C1=CC=CC=C1 RCYBMSQOSGJZLO-BGWNEDDSSA-N 0.000 claims description 4
229950007939 levophenacylmorphan Drugs 0.000 claims description 4
229960003406 levorphanol Drugs 0.000 claims description 4
229950010274 lofentanil Drugs 0.000 claims description 4
IMYHGORQCPYVBZ-NLFFAJNJSA-N lofentanil Chemical compound CCC(=O)N([C@@]1([C@@H](CN(CCC=2C=CC=CC=2)CC1)C)C(=O)OC)C1=CC=CC=C1 IMYHGORQCPYVBZ-NLFFAJNJSA-N 0.000 claims description 4
229960000365 meptazinol Drugs 0.000 claims description 4
JLICHNCFTLFZJN-HNNXBMFYSA-N meptazinol Chemical compound C=1C=CC(O)=CC=1[C@@]1(CC)CCCCN(C)C1 JLICHNCFTLFZJN-HNNXBMFYSA-N 0.000 claims description 4
229950009131 metazocine Drugs 0.000 claims description 4
YGSVZRIZCHZUHB-COLVAYQJSA-N metazocine Chemical compound C1C2=CC=C(O)C=C2[C@]2(C)CCN(C)[C@@]1([H])[C@@H]2C YGSVZRIZCHZUHB-COLVAYQJSA-N 0.000 claims description 4
229960001797 methadone Drugs 0.000 claims description 4
NPZXCTIHHUUEEJ-CMKMFDCUSA-N metopon Chemical compound O([C@@]1(C)C(=O)CC[C@@H]23)C4=C5[C@@]13CCN(C)[C@@H]2CC5=CC=C4O NPZXCTIHHUUEEJ-CMKMFDCUSA-N 0.000 claims description 4
229950006080 metopon Drugs 0.000 claims description 4
229960005181 morphine Drugs 0.000 claims description 4
GODGZZGKTZQSAL-VXFFQEMOSA-N myrophine Chemical compound C([C@@H]1[C@@H]2C=C[C@@H]([C@@H]3OC4=C5[C@]23CCN1C)OC(=O)CCCCCCCCCCCCC)C5=CC=C4OCC1=CC=CC=C1 GODGZZGKTZQSAL-VXFFQEMOSA-N 0.000 claims description 4
229950007471 myrophine Drugs 0.000 claims description 4
229960002009 naproxen Drugs 0.000 claims description 4
CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 4
229960004300 nicomorphine Drugs 0.000 claims description 4
HNDXBGYRMHRUFN-CIVUWBIHSA-N nicomorphine Chemical compound O([C@H]1C=C[C@H]2[C@H]3CC=4C5=C(C(=CC=4)OC(=O)C=4C=NC=CC=4)O[C@@H]1[C@]52CCN3C)C(=O)C1=CC=CN=C1 HNDXBGYRMHRUFN-CIVUWBIHSA-N 0.000 claims description 4
229950007418 norpipanone Drugs 0.000 claims description 4
WCDSHELZWCOTMI-UHFFFAOYSA-N norpipanone Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)CC)CCN1CCCCC1 WCDSHELZWCOTMI-UHFFFAOYSA-N 0.000 claims description 4
229960001027 opium Drugs 0.000 claims description 4
229960002085 oxycodone Drugs 0.000 claims description 4
229960005118 oxymorphone Drugs 0.000 claims description 4
VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 claims description 4
229960005301 pentazocine Drugs 0.000 claims description 4
229960000482 pethidine Drugs 0.000 claims description 4
229960003893 phenacetin Drugs 0.000 claims description 4
LOXCOAXRHYDLOW-UHFFFAOYSA-N phenadoxone Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)CC)CC(C)N1CCOCC1 LOXCOAXRHYDLOW-UHFFFAOYSA-N 0.000 claims description 4
229950004540 phenadoxone Drugs 0.000 claims description 4
ZQHYKVKNPWDQSL-KNXBSLHKSA-N phenazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CCC1=CC=CC=C1 ZQHYKVKNPWDQSL-KNXBSLHKSA-N 0.000 claims description 4
229960000897 phenazocine Drugs 0.000 claims description 4
CFBQYWXPZVQQTN-QPTUXGOLSA-N phenomorphan Chemical compound C([C@]12CCCC[C@H]1[C@H]1CC3=CC=C(C=C32)O)CN1CCC1=CC=CC=C1 CFBQYWXPZVQQTN-QPTUXGOLSA-N 0.000 claims description 4
229950011496 phenomorphan Drugs 0.000 claims description 4
IPOPQVVNCFQFRK-UHFFFAOYSA-N phenoperidine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(O)C1=CC=CC=C1 IPOPQVVNCFQFRK-UHFFFAOYSA-N 0.000 claims description 4
229960004315 phenoperidine Drugs 0.000 claims description 4
PXXKIYPSXYFATG-UHFFFAOYSA-N piminodine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCCNC1=CC=CC=C1 PXXKIYPSXYFATG-UHFFFAOYSA-N 0.000 claims description 4
229950006445 piminodine Drugs 0.000 claims description 4
229960002702 piroxicam Drugs 0.000 claims description 4
QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims description 4
ZBAFFZBKCMWUHM-UHFFFAOYSA-N propiram Chemical compound C=1C=CC=NC=1N(C(=O)CC)C(C)CN1CCCCC1 ZBAFFZBKCMWUHM-UHFFFAOYSA-N 0.000 claims description 4
229950003779 propiram Drugs 0.000 claims description 4
229960004739 sufentanil Drugs 0.000 claims description 4
229960001402 tilidine Drugs 0.000 claims description 4
229960004380 tramadol Drugs 0.000 claims description 4
TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 claims description 4
229920001903 high density polyethylene Polymers 0.000 claims description 3
239000004700 high-density polyethylene Substances 0.000 claims description 3
230000019612 pigmentation Effects 0.000 claims description 3
LQGIXNQCOXNCRP-UHFFFAOYSA-N dioxaphetyl butyrate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)OCC)CCN1CCOCC1 LQGIXNQCOXNCRP-UHFFFAOYSA-N 0.000 claims 1
PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 claims 1
238000000034 method Methods 0.000 abstract description 53
238000000638 solvent extraction Methods 0.000 abstract description 5
230000002035 prolonged effect Effects 0.000 abstract description 3
230000000202 analgesic effect Effects 0.000 abstract 1
239000003826 tablet Substances 0.000 description 108
238000013103 analytical ultracentrifugation Methods 0.000 description 40
239000007888 film coating Substances 0.000 description 39
238000009501 film coating Methods 0.000 description 39
125000000217 alkyl group Chemical group 0.000 description 35
230000008569 process Effects 0.000 description 26
239000010410 layer Substances 0.000 description 25
230000036470 plasma concentration Effects 0.000 description 25
229920003134 Eudragit® polymer Polymers 0.000 description 24
229920003091 Methocel™ Polymers 0.000 description 22
229960003943 hypromellose Drugs 0.000 description 22
239000004480 active ingredient Substances 0.000 description 21
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 19
229920000058 polyacrylate Polymers 0.000 description 18
239000007787 solid Substances 0.000 description 18
239000002253 acid Substances 0.000 description 17
239000000843 powder Substances 0.000 description 16
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 15
239000000463 material Substances 0.000 description 15
238000002156 mixing Methods 0.000 description 15
239000000725 suspension Substances 0.000 description 15
239000002245 particle Substances 0.000 description 14
238000006467 substitution reaction Methods 0.000 description 14
239000007941 film coated tablet Substances 0.000 description 13
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 13
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 12
229920002678 cellulose Polymers 0.000 description 12
238000004519 manufacturing process Methods 0.000 description 12
239000000155 melt Substances 0.000 description 12
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 12
239000000811 xylitol Substances 0.000 description 12
235000010447 xylitol Nutrition 0.000 description 12
229960002675 xylitol Drugs 0.000 description 12
NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 11
125000003118 aryl group Chemical group 0.000 description 11
238000003490 calendering Methods 0.000 description 11
239000011248 coating agent Substances 0.000 description 11
238000000576 coating method Methods 0.000 description 11
239000000178 monomer Substances 0.000 description 11
229920003156 Eudragit® RL PO Polymers 0.000 description 10
150000001875 compounds Chemical class 0.000 description 10
230000001276 controlling effect Effects 0.000 description 10
239000006185 dispersion Substances 0.000 description 10
239000000243 solution Substances 0.000 description 10
229920003151 Eudragit® RL polymer Polymers 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
DNKKLDKIFMDAPT-UHFFFAOYSA-N n,n-dimethylmethanamine;2-methylprop-2-enoic acid Chemical compound CN(C)C.CC(=C)C(O)=O.CC(=C)C(O)=O DNKKLDKIFMDAPT-UHFFFAOYSA-N 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
229920003152 Eudragit® RS polymer Polymers 0.000 description 8
FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
239000001913 cellulose Substances 0.000 description 7
229920003086 cellulose ether Polymers 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
238000000605 extraction Methods 0.000 description 7
229920000609 methyl cellulose Polymers 0.000 description 7
235000010981 methylcellulose Nutrition 0.000 description 7
229920003096 Methocel™ K100M Polymers 0.000 description 6
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
125000002091 cationic group Chemical group 0.000 description 6
HEBKCHPVOIAQTA-NGQZWQHPSA-N d-xylitol Chemical compound OC[C@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-NGQZWQHPSA-N 0.000 description 6
235000014113 dietary fatty acids Nutrition 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000000194 fatty acid Substances 0.000 description 6
229930195729 fatty acid Natural products 0.000 description 6
239000012530 fluid Substances 0.000 description 6
239000004615 ingredient Substances 0.000 description 6
239000001923 methylcellulose Substances 0.000 description 6
230000007935 neutral effect Effects 0.000 description 6
230000009467 reduction Effects 0.000 description 6
239000006104 solid solution Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000000126 substance Substances 0.000 description 6
RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000007900 aqueous suspension Substances 0.000 description 5
239000008280 blood Substances 0.000 description 5
210000004369 blood Anatomy 0.000 description 5
NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 5
238000013270 controlled release Methods 0.000 description 5
125000000524 functional group Chemical group 0.000 description 5
229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
239000001267 polyvinylpyrrolidone Substances 0.000 description 5
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000005507 spraying Methods 0.000 description 5
238000013268 sustained release Methods 0.000 description 5
239000012730 sustained-release form Substances 0.000 description 5
SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 4
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 4
SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 4
229920003163 Eudragit® NE 30 D Polymers 0.000 description 4
CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 4
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
229920006243 acrylic copolymer Polymers 0.000 description 4
239000000654 additive Substances 0.000 description 4
125000005250 alkyl acrylate group Chemical group 0.000 description 4
229920013820 alkyl cellulose Polymers 0.000 description 4
239000004359 castor oil Substances 0.000 description 4
235000019438 castor oil Nutrition 0.000 description 4
238000009826 distribution Methods 0.000 description 4
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 4
238000009499 grossing Methods 0.000 description 4
229920001983 poloxamer Polymers 0.000 description 4
229920001993 poloxamer 188 Polymers 0.000 description 4
229920001451 polypropylene glycol Polymers 0.000 description 4
150000005846 sugar alcohols Chemical class 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
229920002554 vinyl polymer Polymers 0.000 description 4
IGPROYLOGZTOAM-UHFFFAOYSA-N 3-phenylsulfanylpropanoic acid Chemical compound OC(=O)CCSC1=CC=CC=C1 IGPROYLOGZTOAM-UHFFFAOYSA-N 0.000 description 3
SERLAGPUMNYUCK-YJOKQAJESA-N 6-O-alpha-D-glucopyranosyl-D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-YJOKQAJESA-N 0.000 description 3
JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 3
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 3
229920003136 Eudragit® L polymer Polymers 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
229920002556 Polyethylene Glycol 300 Polymers 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
102100035115 Testin Human genes 0.000 description 3
101710070533 Testin Proteins 0.000 description 3
XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 3
239000008186 active pharmaceutical agent Substances 0.000 description 3
229940035676 analgesics Drugs 0.000 description 3
239000000730 antalgic agent Substances 0.000 description 3
238000013459 approach Methods 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
235000019658 bitter taste Nutrition 0.000 description 3
229920001400 block copolymer Polymers 0.000 description 3
CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 3
238000005336 cracking Methods 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
239000013583 drug formulation Substances 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 3
230000002496 gastric effect Effects 0.000 description 3
210000001035 gastrointestinal tract Anatomy 0.000 description 3
239000008187 granular material Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
125000002768 hydroxyalkyl group Chemical group 0.000 description 3
238000010348 incorporation Methods 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 3
239000002609 medium Substances 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
229940117841 methacrylic acid copolymer Drugs 0.000 description 3
229920003145 methacrylic acid copolymer Polymers 0.000 description 3
238000003801 milling Methods 0.000 description 3
GSGDTSDELPUTKU-UHFFFAOYSA-N nonoxybenzene Chemical compound CCCCCCCCCOC1=CC=CC=C1 GSGDTSDELPUTKU-UHFFFAOYSA-N 0.000 description 3
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 3
229940044519 poloxamer 188 Drugs 0.000 description 3
125000003367 polycyclic group Chemical group 0.000 description 3
239000008389 polyethoxylated castor oil Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 3
229920000136 polysorbate Polymers 0.000 description 3
238000012429 release testing Methods 0.000 description 3
238000003860 storage Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
230000003746 surface roughness Effects 0.000 description 3
239000004094 surface-active agent Substances 0.000 description 3
238000011282 treatment Methods 0.000 description 3
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Polymers OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 description 2
OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 2
RUMACXVDVNRZJZ-UHFFFAOYSA-N 2-methylpropyl 2-methylprop-2-enoate Chemical compound CC(C)COC(=O)C(C)=C RUMACXVDVNRZJZ-UHFFFAOYSA-N 0.000 description 2
CFVWNXQPGQOHRJ-UHFFFAOYSA-N 2-methylpropyl prop-2-enoate Chemical compound CC(C)COC(=O)C=C CFVWNXQPGQOHRJ-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
229910002016 Aerosil® 200 Inorganic materials 0.000 description 2
NYNKCGWJPNZJMI-UHFFFAOYSA-N Clebopride malate Chemical compound [O-]C(=O)C(O)CC(O)=O.COC1=CC(N)=C(Cl)C=C1C(=O)NC1CC[NH+](CC=2C=CC=CC=2)CC1 NYNKCGWJPNZJMI-UHFFFAOYSA-N 0.000 description 2
239000001856 Ethyl cellulose Substances 0.000 description 2
229920003149 Eudragit® E 100 Polymers 0.000 description 2
229920003139 Eudragit® L 100 Polymers 0.000 description 2
229920003155 Eudragit® RL 100 Polymers 0.000 description 2
229920003159 Eudragit® RS 100 Polymers 0.000 description 2
229920003160 Eudragit® RS PO Polymers 0.000 description 2
229920003141 Eudragit® S 100 Polymers 0.000 description 2
RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
229920001213 Polysorbate 20 Polymers 0.000 description 2
229920001214 Polysorbate 60 Polymers 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
229940086209 acetaminophen 120 mg Drugs 0.000 description 2
229940086216 acetaminophen 150 mg Drugs 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
230000008901 benefit Effects 0.000 description 2
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000011247 coating layer Substances 0.000 description 2
239000008119 colloidal silica Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004663 dialkyl amino group Chemical group 0.000 description 2
235000005911 diet Nutrition 0.000 description 2
230000037213 diet Effects 0.000 description 2
239000007884 disintegrant Substances 0.000 description 2
229940088679 drug related substance Drugs 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 2
235000019325 ethyl cellulose Nutrition 0.000 description 2
229920001249 ethyl cellulose Polymers 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
239000011888 foil Substances 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
210000004051 gastric juice Anatomy 0.000 description 2
239000011521 glass Substances 0.000 description 2
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
229920001519 homopolymer Polymers 0.000 description 2
125000003010 ionic group Chemical group 0.000 description 2
235000013980 iron oxide Nutrition 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
239000000905 isomalt Substances 0.000 description 2
235000010439 isomalt Nutrition 0.000 description 2
HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
238000011068 loading method Methods 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
125000005395 methacrylic acid group Chemical group 0.000 description 2
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
239000003607 modifier Substances 0.000 description 2
125000000896 monocarboxylic acid group Chemical group 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000003401 opiate antagonist Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
239000008180 pharmaceutical surfactant Substances 0.000 description 2
229920003023 plastic Polymers 0.000 description 2
239000004033 plastic Substances 0.000 description 2
239000004014 plasticizer Substances 0.000 description 2
229960000502 poloxamer Drugs 0.000 description 2
229920001992 poloxamer 407 Polymers 0.000 description 2
229920000520 poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Polymers 0.000 description 2
229920000573 polyethylene Polymers 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
BOQSSGDQNWEFSX-UHFFFAOYSA-N propan-2-yl 2-methylprop-2-enoate Chemical compound CC(C)OC(=O)C(C)=C BOQSSGDQNWEFSX-UHFFFAOYSA-N 0.000 description 2
LYBIZMNPXTXVMV-UHFFFAOYSA-N propan-2-yl prop-2-enoate Chemical compound CC(C)OC(=O)C=C LYBIZMNPXTXVMV-UHFFFAOYSA-N 0.000 description 2
NHARPDSAXCBDDR-UHFFFAOYSA-N propyl 2-methylprop-2-enoate Chemical compound CCCOC(=O)C(C)=C NHARPDSAXCBDDR-UHFFFAOYSA-N 0.000 description 2
PNXMTCDJUBJHQJ-UHFFFAOYSA-N propyl prop-2-enoate Chemical compound CCCOC(=O)C=C PNXMTCDJUBJHQJ-UHFFFAOYSA-N 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
238000005070 sampling Methods 0.000 description 2
238000004062 sedimentation Methods 0.000 description 2
229960002920 sorbitol Drugs 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
229910001220 stainless steel Inorganic materials 0.000 description 2
239000010935 stainless steel Substances 0.000 description 2
239000000021 stimulant Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
230000009747 swallowing Effects 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
SJMYWORNLPSJQO-UHFFFAOYSA-N tert-butyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(C)(C)C SJMYWORNLPSJQO-UHFFFAOYSA-N 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
229940126585 therapeutic drug Drugs 0.000 description 2
125000004001 thioalkyl group Chemical group 0.000 description 2
239000004408 titanium dioxide Substances 0.000 description 2
230000007704 transition Effects 0.000 description 2
238000001665 trituration Methods 0.000 description 2
238000000825 ultraviolet detection Methods 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
LBZKTMXJEFCCBK-PMDBGEGLSA-N (4R,4aR,7aR,12bS)-9-methoxy-3-methyl-3-oxido-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-7-one Chemical compound COc1ccc2C[C@@H]3[C@@H]4CCC(=O)[C@@H]5Oc1c2[C@]45CC[N+]3(C)[O-] LBZKTMXJEFCCBK-PMDBGEGLSA-N 0.000 description 1
OPEYVVLXBYHKDO-DANDVKJOSA-N (4r,4ar,7ar,12bs)-9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one;(2r,3r)-2,3-dihydroxybutanedioic acid;2-[4-(2-methylpropyl)phenyl]propanoic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CC(C)CC1=CC=C(C(C)C(O)=O)C=C1.C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC OPEYVVLXBYHKDO-DANDVKJOSA-N 0.000 description 1
GQIVTWIJJVAWQR-DANDVKJOSA-N (4r,4ar,7ar,12bs)-9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one;(2r,3r)-2,3-dihydroxybutanedioic acid;n-(4-hydroxyphenyl)acetamide Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CC(=O)NC1=CC=C(O)C=C1.C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC GQIVTWIJJVAWQR-DANDVKJOSA-N 0.000 description 1
RKUNBYITZUJHSG-FXUDXRNXSA-N (S)-atropine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@H]3CC[C@@H](C2)N3C)=CC=CC=C1 RKUNBYITZUJHSG-FXUDXRNXSA-N 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
QIZPVNNYFKFJAD-UHFFFAOYSA-N 1-chloro-2-prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1Cl QIZPVNNYFKFJAD-UHFFFAOYSA-N 0.000 description 1
CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 1
FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 1
WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
JNYAEWCLZODPBN-UHFFFAOYSA-N 2-(1,2-dihydroxyethyl)oxolane-3,4-diol Polymers OCC(O)C1OCC(O)C1O JNYAEWCLZODPBN-UHFFFAOYSA-N 0.000 description 1
WROUWQQRXUBECT-UHFFFAOYSA-N 2-ethylacrylic acid Chemical compound CCC(=C)C(O)=O WROUWQQRXUBECT-UHFFFAOYSA-N 0.000 description 1
CTXGTHVAWRBISV-UHFFFAOYSA-N 2-hydroxyethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCO CTXGTHVAWRBISV-UHFFFAOYSA-N 0.000 description 1
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
PVXPPJIGRGXGCY-DJHAAKORSA-N 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@](O)(CO)O1 PVXPPJIGRGXGCY-DJHAAKORSA-N 0.000 description 1
XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
229910002012 Aerosil® Inorganic materials 0.000 description 1
229930003347 Atropine Natural products 0.000 description 1
MIUONHYLGGPXIY-SSXWPEOMSA-N C1=CC(OC)=C2C=3[C@@]45[C@@H](O2)C(=O)CC[C@H]4[C@@H](CC13)N(C)CC5.C5=CC(OC)=C1C=3[C@@]42[C@@H](O1)C(=O)CC[C@H]4[C@@H](CC53)N(C)CC2.C2=CC(OC)=C5C=3[C@@]41[C@@H](O5)C(=O)CC[C@H]4[C@@H](CC23)N(C)CC1.C1=CC(OC)=C2C=3[C@@]45[C@@H](O2)C(=O)CC[C@H]4[C@@H](CC13)N(C)CC5 Chemical compound C1=CC(OC)=C2C=3[C@@]45[C@@H](O2)C(=O)CC[C@H]4[C@@H](CC13)N(C)CC5.C5=CC(OC)=C1C=3[C@@]42[C@@H](O1)C(=O)CC[C@H]4[C@@H](CC53)N(C)CC2.C2=CC(OC)=C5C=3[C@@]41[C@@H](O5)C(=O)CC[C@H]4[C@@H](CC23)N(C)CC1.C1=CC(OC)=C2C=3[C@@]45[C@@H](O2)C(=O)CC[C@H]4[C@@H](CC13)N(C)CC5 MIUONHYLGGPXIY-SSXWPEOMSA-N 0.000 description 1
229920008347 Cellulose acetate propionate Polymers 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
108010065372 Dynorphins Proteins 0.000 description 1
229920005682 EO-PO block copolymer Polymers 0.000 description 1
229920003119 EUDRAGIT E PO Polymers 0.000 description 1
108010049140 Endorphins Proteins 0.000 description 1
102000009025 Endorphins Human genes 0.000 description 1
108010092674 Enkephalins Proteins 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
229920003148 Eudragit® E polymer Polymers 0.000 description 1
229920003135 Eudragit® L 100-55 Polymers 0.000 description 1
229920003164 Eudragit® NE 40 D Polymers 0.000 description 1
229920003157 Eudragit® RL 30 D Polymers 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical class C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
229920002774 Maltodextrin Polymers 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
108010093625 Opioid Peptides Proteins 0.000 description 1
102000001490 Opioid Peptides Human genes 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
229920003072 Plasdone™ povidone Polymers 0.000 description 1
229920002507 Poloxamer 124 Polymers 0.000 description 1
229920002511 Poloxamer 237 Polymers 0.000 description 1
229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
229920000954 Polyglycolide Polymers 0.000 description 1
229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 1
229920002700 Polyoxyl 60 hydrogenated castor oil Polymers 0.000 description 1
229920001219 Polysorbate 40 Polymers 0.000 description 1
229920003110 Primojel Polymers 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
241000030538 Thecla Species 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 description 1
KGUHOFWIXKIURA-VQXBOQCVSA-N [(2r,3s,4s,5r,6r)-6-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl dodecanoate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)CCCCCCCCCCC)O[C@@H]1O[C@@]1(CO)[C@@H](O)[C@H](O)[C@@H](CO)O1 KGUHOFWIXKIURA-VQXBOQCVSA-N 0.000 description 1
FOLJTMYCYXSPFQ-CJKAUBRRSA-N [(2r,3s,4s,5r,6r)-6-[(2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-(octadecanoyloxymethyl)oxolan-2-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl octadecanoate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)CCCCCCCCCCCCCCCCC)O[C@@H]1O[C@@]1(COC(=O)CCCCCCCCCCCCCCCCC)[C@@H](O)[C@H](O)[C@@H](CO)O1 FOLJTMYCYXSPFQ-CJKAUBRRSA-N 0.000 description 1
NPTLAYTZMHJJDP-KTKRTIGZSA-N [3-[3-[3-[3-[3-[3-[3-[3-[3-(2,3-dihydroxypropoxy)-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)CO NPTLAYTZMHJJDP-KTKRTIGZSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000001252 acrylic acid derivatives Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
238000013019 agitation Methods 0.000 description 1
239000000556 agonist Substances 0.000 description 1
235000013334 alcoholic beverage Nutrition 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
150000001346 alkyl aryl ethers Chemical class 0.000 description 1
150000005215 alkyl ethers Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000000181 anti-adherent effect Effects 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
230000001174 ascending effect Effects 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
229960000396 atropine Drugs 0.000 description 1
208000029618 autoimmune pulmonary alveolar proteinosis Diseases 0.000 description 1
125000002511 behenyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000004067 bulking agent Substances 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
229920006217 cellulose acetate butyrate Polymers 0.000 description 1
229940081734 cellulose acetate phthalate Drugs 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
229940000425 combination drug Drugs 0.000 description 1
239000000470 constituent Substances 0.000 description 1
LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
238000005520 cutting process Methods 0.000 description 1
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
239000003599 detergent Substances 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
230000001079 digestive effect Effects 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000009837 dry grinding Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
JMNJYGMAUMANNW-FIXZTSJVSA-N dynorphin a Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 JMNJYGMAUMANNW-FIXZTSJVSA-N 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000004049 embossing Methods 0.000 description 1
238000004945 emulsification Methods 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
UIWXSTHGICQLQT-UHFFFAOYSA-N ethenyl propanoate Chemical compound CCC(=O)OC=C UIWXSTHGICQLQT-UHFFFAOYSA-N 0.000 description 1
GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 1
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
230000029142 excretion Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
230000037406 food intake Effects 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
230000036541 health Effects 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
229930005342 hyoscyamine Natural products 0.000 description 1
229960003210 hyoscyamine Drugs 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
239000012729 immediate-release (IR) formulation Substances 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000007373 indentation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229920000831 ionic polymer Polymers 0.000 description 1
VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
238000004898 kneading Methods 0.000 description 1
TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 1
239000004611 light stabiliser Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000007726 management method Methods 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
229960001855 mannitol Drugs 0.000 description 1
125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000002483 medication Methods 0.000 description 1
229960001252 methamphetamine Drugs 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
238000001000 micrograph Methods 0.000 description 1
244000309715 mini pig Species 0.000 description 1
230000036651 mood Effects 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000004081 narcotic agent Substances 0.000 description 1
230000003533 narcotic effect Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
ZPIRTVJRHUMMOI-UHFFFAOYSA-N octoxybenzene Chemical compound CCCCCCCCOC1=CC=CC=C1 ZPIRTVJRHUMMOI-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
239000003399 opiate peptide Substances 0.000 description 1
238000000879 optical micrograph Methods 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
238000003921 particle size analysis Methods 0.000 description 1
235000011837 pasties Nutrition 0.000 description 1
229940094335 peg-200 dilaurate Drugs 0.000 description 1
125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000002572 peristaltic effect Effects 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
229960002695 phenobarbital Drugs 0.000 description 1
229950000688 phenothiazine Drugs 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
229940093448 poloxamer 124 Drugs 0.000 description 1
229940044476 poloxamer 407 Drugs 0.000 description 1
229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
229920000233 poly(alkylene oxides) Polymers 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
229920000223 polyglycerol Polymers 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
229920005606 polypropylene copolymer Polymers 0.000 description 1
229920002689 polyvinyl acetate Polymers 0.000 description 1
239000011118 polyvinyl acetate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000000955 prescription drug Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
229960003908 pseudoephedrine Drugs 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
230000005180 public health Effects 0.000 description 1
238000010298 pulverizing process Methods 0.000 description 1
239000008213 purified water Substances 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
239000013643 reference control Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
229960002646 scopolamine Drugs 0.000 description 1
238000010008 shearing Methods 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
238000007711 solidification Methods 0.000 description 1
230000008023 solidification Effects 0.000 description 1
JNYAEWCLZODPBN-CTQIIAAMSA-N sorbitan Polymers OCC(O)C1OCC(O)[C@@H]1O JNYAEWCLZODPBN-CTQIIAAMSA-N 0.000 description 1
229940035044 sorbitan monolaurate Drugs 0.000 description 1
235000011067 sorbitan monolaureate Nutrition 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
239000001570 sorbitan monopalmitate Substances 0.000 description 1
235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
229940031953 sorbitan monopalmitate Drugs 0.000 description 1
229950011392 sorbitan stearate Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
238000012066 statistical methodology Methods 0.000 description 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000004575 stone Substances 0.000 description 1
229940032085 sucrose monolaurate Drugs 0.000 description 1
229940035023 sucrose monostearate Drugs 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000019640 taste Nutrition 0.000 description 1
238000002076 thermal analysis method Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004448 titration Methods 0.000 description 1
LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
USFMMZYROHDWPJ-UHFFFAOYSA-N trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium Chemical group CC(=C)C(=O)OCC[N+](C)(C)C USFMMZYROHDWPJ-UHFFFAOYSA-N 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
235000013522 vodka Nutrition 0.000 description 1
230000036642 wellbeing Effects 0.000 description 1
238000001238 wet grinding Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse

Landscapes

Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Pain & Pain Management (AREA)
Addiction (AREA)
Organic Chemistry (AREA)
Emergency Medicine (AREA)
Psychiatry (AREA)
Medicinal Preparation (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA2690829A 2007-07-20 2007-07-20 Formulations d'analgesiques non opioides et d'analgesiques opioides captifs Abandoned CA2690829A1 (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PCT/US2007/073957 WO2009014534A1 (fr)	2007-07-20	2007-07-20	Formulations d'analgésiques non opioïdes et d'analgésiques opioïdes captifs

Publications (1)

Publication Number	Publication Date
CA2690829A1 true CA2690829A1 (fr)	2009-01-29

Family

ID=39338644

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2690829A Abandoned CA2690829A1 (fr)	2007-07-20	2007-07-20	Formulations d'analgesiques non opioides et d'analgesiques opioides captifs

Country Status (14)

Country	Link
EP (1)	EP2182928A1 (fr)
JP (1)	JP2010534204A (fr)
KR (1)	KR20100055431A (fr)
CN (1)	CN101917977B (fr)
AU (1)	AU2007356880A1 (fr)
BR (1)	BRPI0721940A2 (fr)
CA (1)	CA2690829A1 (fr)
IL (1)	IL202680A0 (fr)
MX (1)	MX2010000803A (fr)
NZ (1)	NZ581767A (fr)
RU (1)	RU2477995C2 (fr)
TW (1)	TW200904431A (fr)
WO (1)	WO2009014534A1 (fr)
ZA (1)	ZA200908900B (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US9492444B2 (en)	2013-12-17	2016-11-15	Pharmaceutical Manufacturing Research Services, Inc.	Extruded extended release abuse deterrent pill
US9707184B2 (en)	2014-07-17	2017-07-18	Pharmaceutical Manufacturing Research Services, Inc.	Immediate release abuse deterrent liquid fill dosage form
US10172797B2 (en)	2013-12-17	2019-01-08	Pharmaceutical Manufacturing Research Services, Inc.	Extruded extended release abuse deterrent pill
US10195153B2 (en)	2013-08-12	2019-02-05	Pharmaceutical Manufacturing Research Services, Inc.	Extruded immediate release abuse deterrent pill
US10959958B2 (en)	2014-10-20	2021-03-30	Pharmaceutical Manufacturing Research Services, Inc.	Extended release abuse deterrent liquid fill dosage form

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7776314B2 (en)	2002-06-17	2010-08-17	Grunenthal Gmbh	Abuse-proofed dosage system
DE102005005446A1 (de)	2005-02-04	2006-08-10	Grünenthal GmbH	Bruchfeste Darreichungsformen mit retardierter Freisetzung
US20070048228A1 (en)	2003-08-06	2007-03-01	Elisabeth Arkenau-Maric	Abuse-proofed dosage form
DE10336400A1 (de)	2003-08-06	2005-03-24	Grünenthal GmbH	Gegen Missbrauch gesicherte Darreichungsform
DE10361596A1 (de)	2003-12-24	2005-09-29	Grünenthal GmbH	Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
DE102004032049A1 (de)	2004-07-01	2006-01-19	Grünenthal GmbH	Gegen Missbrauch gesicherte, orale Darreichungsform
DE102005005449A1 (de)	2005-02-04	2006-08-10	Grünenthal GmbH	Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
DE102007011485A1 (de)	2007-03-07	2008-09-11	Grünenthal GmbH	Darreichungsform mit erschwertem Missbrauch
US8383152B2 (en)	2008-01-25	2013-02-26	Gruenenthal Gmbh	Pharmaceutical dosage form
SI2273983T1 (sl)	2008-05-09	2016-11-30	Gruenenthal Gmbh	Postopek za pripravo intermediatne praškaste formulacije in končne trdne odmerne oblike z uporabo stopnje strjevanja z razprševanjem
AU2010275755B2 (en)	2009-07-22	2014-04-24	Grünenthal GmbH	Oxidation-stabilized tamper-resistant dosage form
TW201105316A (en)	2009-07-22	2011-02-16	Gruenenthal Gmbh	Hot-melt extruded pharmaceutical dosage form
CN103179954A (zh)	2010-09-02	2013-06-26	格吕伦塔尔有限公司	包含阴离子聚合物的抗破碎剂型
MX2013002377A (es)	2010-09-02	2013-04-29	Gruenenthal Gmbh	Forma de dosificacion resistente a manipulacion que comprende una sal inorganica.
RS56344B1 (sr) *	2010-12-22	2017-12-29	Purdue Pharma Lp	Obloženi dozni oblici sa kontrolisanim oslobađanjem otporni na zloupotrebu
RS56527B1 (sr)	2011-07-29	2018-02-28	Gruenenthal Gmbh	Tableta za trenutno oslobađanje leka rezistentna na zloupotrebu
US10201502B2 (en)	2011-07-29	2019-02-12	Gruenenthal Gmbh	Tamper-resistant tablet providing immediate drug release
FR2979242A1 (fr) *	2011-08-29	2013-03-01	Sanofi Sa	Comprime contre l'usage abusif, a base de paracetamol et d'oxycodone
MX356421B (es)	2012-02-28	2018-05-29	Gruenenthal Gmbh	Forma de dosificacion resistente a la manipulacion indebida que comprende un compuesto farmacologicamente activo y un polimero anionico.
EA201401139A1 (ru)	2012-04-18	2015-03-31	Грюненталь Гмбх	Устойчивая к разрушению и к сбросу дозы фармацевтическая лекарственная форма
US10064945B2 (en)	2012-05-11	2018-09-04	Gruenenthal Gmbh	Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
CA2913209A1 (fr) *	2013-05-29	2014-12-04	Grunenthal Gmbh	Forme dosifiee inviolable a profil de liberation bimodale
BR112015026549A2 (pt)	2013-05-29	2017-07-25	Gruenenthal Gmbh	forma de dosagem à prova de violação contendo uma ou mais partículas
CA2917136C (fr)	2013-07-12	2022-05-31	Grunenthal Gmbh	Forme posologique inviolable contenant un polymere d'ethylene-acetate de vinyle
PT3069733T (pt) *	2013-11-13	2022-11-09	National Defense Education And Res Foundation	Nova composição de composto de acetaminofeno sem efeito secundário para o fígado
WO2015078891A1 (fr)	2013-11-26	2015-06-04	Farmaceutici Formenti S.P.A.	Préparation de composition pharmaceutique en poudre par cryo-broyage
WO2015173195A1 (fr)	2014-05-12	2015-11-19	Grünenthal GmbH	Formulation pour capsule à libération immédiate résistant aux manipulations illicites comprenant du tapentadol
MX2016015417A (es)	2014-05-26	2017-02-22	Gruenenthal Gmbh	Multiparticulas protegidas contra vertido de dosis etanolico.
EP3285745A1 (fr)	2015-04-24	2018-02-28	Grünenthal GmbH	Forme galénique inviolable avec libération immédiate et résistance à l'extraction par solvant.
JP2018520165A (ja) *	2015-07-10	2018-07-26	サン、ファーマ、アドバンスト、リサーチ、カンパニー、リミテッドＳｕｎＰｈａｒｍａＡｄｖａｎｃｅｄＲｅｓｅａｒｃｈＣｏｍｐａｎｙＬｉｍｉｔｅｄ	ヒドロコドンの多数錠剤乱用抵抗性即時放出型固体投薬形態物
JP2018526414A (ja)	2015-09-10	2018-09-13	グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング	乱用抑止性の即放性製剤を用いた経口過剰摂取に対する保護
SE541800C2 (en)	2018-04-20	2019-12-17	Scania Cv Ab	A method of controlling a powertrain, a control arrangement, a vehicle, a computer program and a computer-readable medium
JP6858729B2 (ja) *	2018-05-25	2021-04-14	▲財▼▲団▼法人国防教育研究基金会ＮａｔｉｏｎａｌＤｅｆｅｎｓｅＥｄｕｃａｔｉｏｎＡｎｄＲｅｓｅａｒｃｈＦｏｕｎｄａｔｉｏｎ	肝臓に対する副作用がない、新しいアセトアミノフェン複合組成
IT201800011125A1 (it) *	2018-12-14	2020-06-14	Dpl Pharma S P A	Composizioni farmaceutiche orali solide comprendenti matrici monolitiche complesse per la somministrazione cronotropica di medicamenti nel tratto gastroenterico

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE526950T1 (de) *	1999-10-29	2011-10-15	Euro Celtique Sa	Hydrocodon-formulierungen mit gesteuerter freisetzung
US20030092724A1 (en) *	2001-09-18	2003-05-15	Huaihung Kao	Combination sustained release-immediate release oral dosage forms with an opioid analgesic and a non-opioid analgesic
NZ546148A (en) *	2003-09-26	2009-05-31	Alza Corp	Drug coating providing high drug loading and methods for providing the same
WO2005030181A1 (fr) *	2003-09-26	2005-04-07	Alza Corporation	Preparations a liberation regulee a base d'analgesiques opioides et non opioides
JP5349059B2 (ja) *	2006-03-06	2013-11-20	ポーゼンインコーポレイテッド	薬物の組み合わせを投与するための剤形
US8765178B2 (en) *	2006-07-19	2014-07-01	Watson Laboratories, Inc.	Controlled release formulations and associated methods

2007
- 2007-07-20 MX MX2010000803A patent/MX2010000803A/es not_active Application Discontinuation
- 2007-07-20 BR BRPI0721940-7A patent/BRPI0721940A2/pt not_active IP Right Cessation
- 2007-07-20 JP JP2010516964A patent/JP2010534204A/ja active Pending
- 2007-07-20 EP EP07813144A patent/EP2182928A1/fr not_active Withdrawn
- 2007-07-20 CN CN200780053839XA patent/CN101917977B/zh not_active Expired - Fee Related
- 2007-07-20 CA CA2690829A patent/CA2690829A1/fr not_active Abandoned
- 2007-07-20 KR KR1020107003775A patent/KR20100055431A/ko not_active Application Discontinuation
- 2007-07-20 WO PCT/US2007/073957 patent/WO2009014534A1/fr active Application Filing
- 2007-07-20 AU AU2007356880A patent/AU2007356880A1/en not_active Abandoned
- 2007-07-20 RU RU2010106202/15A patent/RU2477995C2/ru not_active IP Right Cessation
- 2007-07-20 NZ NZ581767A patent/NZ581767A/en not_active IP Right Cessation
2008
- 2008-02-19 TW TW097105831A patent/TW200904431A/zh unknown
2009
- 2009-12-10 IL IL202680A patent/IL202680A0/en unknown
- 2009-12-14 ZA ZA2009/08900A patent/ZA200908900B/en unknown

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US10195153B2 (en)	2013-08-12	2019-02-05	Pharmaceutical Manufacturing Research Services, Inc.	Extruded immediate release abuse deterrent pill
US10639281B2 (en)	2013-08-12	2020-05-05	Pharmaceutical Manufacturing Research Services, Inc.	Extruded immediate release abuse deterrent pill
US9492444B2 (en)	2013-12-17	2016-11-15	Pharmaceutical Manufacturing Research Services, Inc.	Extruded extended release abuse deterrent pill
US10172797B2 (en)	2013-12-17	2019-01-08	Pharmaceutical Manufacturing Research Services, Inc.	Extruded extended release abuse deterrent pill
US10792254B2 (en)	2013-12-17	2020-10-06	Pharmaceutical Manufacturing Research Services, Inc.	Extruded extended release abuse deterrent pill
US9707184B2 (en)	2014-07-17	2017-07-18	Pharmaceutical Manufacturing Research Services, Inc.	Immediate release abuse deterrent liquid fill dosage form
US10959958B2 (en)	2014-10-20	2021-03-30	Pharmaceutical Manufacturing Research Services, Inc.	Extended release abuse deterrent liquid fill dosage form

Also Published As

Publication number	Publication date
IL202680A0 (en)	2010-06-30
ZA200908900B (en)	2014-05-28
WO2009014534A1 (fr)	2009-01-29
CN101917977A (zh)	2010-12-15
KR20100055431A (ko)	2010-05-26
JP2010534204A (ja)	2010-11-04
RU2477995C2 (ru)	2013-03-27
BRPI0721940A2 (pt)	2014-03-18
TW200904431A (en)	2009-02-01
MX2010000803A (es)	2010-06-23
AU2007356880A1 (en)	2009-01-29
EP2182928A1 (fr)	2010-05-12
NZ581767A (en)	2012-05-25
CN101917977B (zh)	2013-05-29
RU2010106202A (ru)	2011-08-27

Legal Events

Date	Code	Title	Description
2012-07-17	EEER	Examination request
2014-09-16	FZDE	Discontinued	Effective date: 20140722

Publication	Publication Date	Title
US20170014348A1 (en)	2017-01-19	Formulations of Nonopioid and Confined Opioid Analgesics
CA2690829A1 (fr)	2009-01-29	Formulations d'analgesiques non opioides et d'analgesiques opioides captifs
US20140120061A1 (en)	2014-05-01	Abuse resistant melt extruded formulation having reduced alcohol interaction
US20100172989A1 (en)	2010-07-08	Abuse resistant melt extruded formulation having reduced alcohol interaction
AU2007205866B2 (en)	2012-11-29	Dosage form and method for the delivery of drugs of abuse
MXPA02004293A (es)	2002-10-31	Formulaciones de hidrocodona de liberacion controlada..
AU2009207579A1 (en)	2009-07-30	Abuse resistant melt extruded formulation having reduced alcohol interaction
AU2014279743A1 (en)	2015-11-26	Modified release formulation
SG178771A1 (en)	2012-03-29	Formulations of nonopioid and confined opioid analgesics