EP1711160A2 - Flat system for using in the oral cavity - Google Patents
Flat system for using in the oral cavityInfo
- Publication number
- EP1711160A2 EP1711160A2 EP05707164A EP05707164A EP1711160A2 EP 1711160 A2 EP1711160 A2 EP 1711160A2 EP 05707164 A EP05707164 A EP 05707164A EP 05707164 A EP05707164 A EP 05707164A EP 1711160 A2 EP1711160 A2 EP 1711160A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- intermediate layer
- flat system
- water
- layer
- flat
- Prior art date
- 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.)
- Withdrawn
Links
- 210000000214 mouth Anatomy 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 25
- 238000004519 manufacturing process Methods 0.000 claims abstract description 15
- 238000007789 sealing Methods 0.000 claims description 33
- 229920003169 water-soluble polymer Polymers 0.000 claims description 33
- 229920000642 polymer Polymers 0.000 claims description 14
- 238000002844 melting Methods 0.000 claims description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 8
- 230000008018 melting Effects 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000002775 capsule Substances 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims description 6
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 5
- 239000004744 fabric Substances 0.000 claims description 5
- 239000000155 melt Substances 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 4
- 235000019437 butane-1,3-diol Nutrition 0.000 claims description 3
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 239000003925 fat Substances 0.000 claims description 3
- 229940051250 hexylene glycol Drugs 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 229960004063 propylene glycol Drugs 0.000 claims description 3
- 239000006215 rectal suppository Substances 0.000 claims description 3
- 150000005846 sugar alcohols Polymers 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 230000011218 segmentation Effects 0.000 claims description 2
- 239000010410 layer Substances 0.000 description 114
- 239000013543 active substance Substances 0.000 description 14
- 235000016257 Mentha pulegium Nutrition 0.000 description 11
- 235000004357 Mentha x piperita Nutrition 0.000 description 11
- 241001479543 Mentha x piperita Species 0.000 description 11
- 235000001050 hortel pimenta Nutrition 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 10
- -1 de-soestrestr Chemical compound 0.000 description 9
- 239000000203 mixture Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 229940116364 hard fat Drugs 0.000 description 5
- 239000013067 intermediate product Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000002699 waste material Substances 0.000 description 4
- 239000012876 carrier material Substances 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 3
- 210000003296 saliva Anatomy 0.000 description 3
- 239000003270 steroid hormone Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- VZWGRQBCURJOMT-UHFFFAOYSA-N Dodecyl acetate Chemical compound CCCCCCCCCCCCOC(C)=O VZWGRQBCURJOMT-UHFFFAOYSA-N 0.000 description 2
- 229920000297 Rayon Polymers 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004049 embossing Methods 0.000 description 2
- 150000002191 fatty alcohols Chemical class 0.000 description 2
- 229920001002 functional polymer Polymers 0.000 description 2
- 229940126601 medicinal product Drugs 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 229940082615 organic nitrates used in cardiac disease Drugs 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 229920006254 polymer film Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- ISHXLNHNDMZNMC-VTKCIJPMSA-N (3e,8r,9s,10r,13s,14s,17r)-13-ethyl-17-ethynyl-3-hydroxyimino-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol Chemical compound O/N=C/1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C\1 ISHXLNHNDMZNMC-VTKCIJPMSA-N 0.000 description 1
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 1
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- BHIZVZJETFVJMJ-UHFFFAOYSA-N 2-hydroxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)O BHIZVZJETFVJMJ-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- CSAVDNHVPJNKTC-UHFFFAOYSA-N 5-methyl-2-propan-2-ylcyclohexan-1-ol;5-methyl-2-propan-2-ylphenol;2,2,4-trimethyl-3-oxabicyclo[2.2.2]octane Chemical compound CC(C)C1CCC(C)CC1O.CC(C)C1=CC=C(C)C=C1O.C1CC2CCC1(C)OC2(C)C CSAVDNHVPJNKTC-UHFFFAOYSA-N 0.000 description 1
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- RSEPBGGWRJCQGY-RBRWEJTLSA-N Estradiol valerate Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 RSEPBGGWRJCQGY-RBRWEJTLSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 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 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 230000006750 UV protection Effects 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- FLZQKRKHLSUHOR-UHFFFAOYSA-N alosetron Chemical compound CC1=NC=N[C]1CN1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FLZQKRKHLSUHOR-UHFFFAOYSA-N 0.000 description 1
- 229960003550 alosetron Drugs 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- AZFLJNIPTRTECV-FUMNGEBKSA-N dienogest Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@](CC3)(O)CC#N)CC3)C3=C21 AZFLJNIPTRTECV-FUMNGEBKSA-N 0.000 description 1
- 229960003309 dienogest Drugs 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- METQSPRSQINEEU-UHFFFAOYSA-N dihydrospirorenone Natural products CC12CCC(C3(CCC(=O)C=C3C3CC33)C)C3C1C1CC1C21CCC(=O)O1 METQSPRSQINEEU-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- QQQMUBLXDAFBRH-UHFFFAOYSA-N dodecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)O QQQMUBLXDAFBRH-UHFFFAOYSA-N 0.000 description 1
- 229960004845 drospirenone Drugs 0.000 description 1
- METQSPRSQINEEU-HXCATZOESA-N drospirenone Chemical compound C([C@]12[C@H]3C[C@H]3[C@H]3[C@H]4[C@@H]([C@]5(CCC(=O)C=C5[C@@H]5C[C@@H]54)C)CC[C@@]31C)CC(=O)O2 METQSPRSQINEEU-HXCATZOESA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229960004766 estradiol valerate Drugs 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- GCKFUYQCUCGESZ-BPIQYHPVSA-N etonogestrel Chemical compound O=C1CC[C@@H]2[C@H]3C(=C)C[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 GCKFUYQCUCGESZ-BPIQYHPVSA-N 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 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
- SIGSPDASOTUPFS-XUDSTZEESA-N gestodene Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](C=C4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 SIGSPDASOTUPFS-XUDSTZEESA-N 0.000 description 1
- 229960005352 gestodene Drugs 0.000 description 1
- RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000011256 inorganic filler Substances 0.000 description 1
- 229910003475 inorganic filler Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000011229 interlayer Substances 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229960004400 levonorgestrel Drugs 0.000 description 1
- 229940076522 listerine Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000010327 methods by industry Methods 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 229960002667 norelgestromin Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229960005343 ondansetron Drugs 0.000 description 1
- 239000012766 organic filler Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 238000009516 primary packaging Methods 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 229940026235 propylene glycol monolaurate Drugs 0.000 description 1
- 239000011814 protection agent Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- NTHPAPBPFQJABD-LLVKDONJSA-N ramosetron Chemical compound C12=CC=CC=C2N(C)C=C1C(=O)[C@H]1CC(NC=N2)=C2CC1 NTHPAPBPFQJABD-LLVKDONJSA-N 0.000 description 1
- 229950001588 ramosetron Drugs 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000002940 repellent Effects 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- VOCBWIIFXDYGNZ-IXKNJLPQSA-N testosterone enanthate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCC)[C@@]1(C)CC2 VOCBWIIFXDYGNZ-IXKNJLPQSA-N 0.000 description 1
- 229960003484 testosterone enanthate Drugs 0.000 description 1
- UDSFVOAUHKGBEK-CNQKSJKFSA-N testosterone undecanoate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCCCCCC)[C@@]1(C)CC2 UDSFVOAUHKGBEK-CNQKSJKFSA-N 0.000 description 1
- 229960000746 testosterone undecanoate Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B27/00—Layered products comprising a layer of synthetic resin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
- A61J3/078—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use into the form of wafers or cachets
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
-
- 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
- A61K31/465—Nicotine; Derivatives thereof
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B38/00—Ancillary operations in connection with laminating processes
- B32B38/16—Drying; Softening; Cleaning
- B32B38/164—Drying
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B2307/00—Properties of the layers or laminate
- B32B2307/70—Other properties
- B32B2307/716—Degradable
- B32B2307/7166—Water-soluble, water-dispersible
Definitions
- the invention relates to a flat system for use in the oral cavity (description)
- the invention relates to a flat system for use in the oral cavity
- Oral cavity and a process for its manufacture This system consists of at least one upper and at least one lower water-soluble cover layer. At least one intermediate layer is provided between the upper and the lower cover layer, which has a smaller area than the cover layers and is cut out along the edge of the flat system.
- PRIOR ART Flat preparations for use in the oral cavity are known. These are typically water-soluble polymer films that quickly disintegrate in the mouth when dissolved in saliva. The polymer film may contain oral or dental care, deodorant, disinfectant or refreshing components which essentially develop their effect in the oral cavity or in the nasopharynx. Products from this area are e.g. B. Eclipse Flash from Wrigley or Listerine PocketPaks from Pfizer.
- Advantageous for pharmaceutical products is the possibility of ingestion without water, the avoidance of swallowing, which is perceived by some people as unpleasant, as well as numerous possibilities for the active ingredient in the mouth or through the mouth through e.g. B. transmucosal uptake into the bloodstream to be effective.
- the water-soluble polymer films are produced from aqueous solution at temperatures of typically up to over 100 ° C. and relatively long drying times, since the removal of water because of its high heat capacity compared to organic ones Solvents is a very energy-intensive process. These process conditions may be unsuitable for volatile or thermally unstable active substances
- the two-dimensional drug forms typically contain the active ingredient in a full-area distribution. If shapes other than rectangular or square are produced, waste is generated by the waste. -
- the loading with the active ingredient leads to an impairment of the film-forming property of the water-soluble polymers (e.g. increase in brittleness) with its increasing concentration, or the loading capacity of the films is reduced by this effect.
- the water-soluble polymer films generally consist of highly functional polymers with a large number of hydroxyl or carboxyl functions on the polymer chain. These highly functional polymers are capable of numerous chemical interactions with active pharmaceutical ingredients, from which stability problems can easily arise.
- the water-soluble polymer films typically require a residual moisture content for processability, which ensures sufficient flexibility or prevents brittleness.
- the residual water content in turn has a negative effect on the chemical stability of active substances in medicinal products.
- the object of the invention is therefore to overcome these disadvantages of conventional flat pharmaceutical products for use in the oral cavity.
- the object is achieved by a flat system for use in the oral cavity, consisting of at least one upper and at least one lower water-soluble cover layer, with between at least one intermediate layer is provided for the upper and lower cover layers.
- This intermediate layer has a smaller surface area than the cover layers in that the intermediate layer is recessed along the edge of the flat system.
- the upper and lower cover layers can be connected to one another by sealing in the edge region of the flat system.
- the width of the sealed seam can be 0.3-3 mm, preferably 0.5-2 mm and particularly preferably 0.75-1.5 mm.
- the total thickness of this planar system at its thickest point can be 50 to 500 ⁇ m, preferably 100 to 300 ⁇ m and particularly preferably 150 to 250 ⁇ m.
- the intermediate layer can be water-soluble and have a melting point between 30 and 120 ° C, preferably between 50 and 100 ° C and particularly preferably between 60 and 90 ° C.
- the intermediate layer can also be water-insoluble.
- Advantageous embodiments of the planar system according to the invention consist of the solid preparation of the intermediate layer, which melts at temperatures between 30 and 45 ° C., preferably between 32 and 40 ° C. and particularly preferably between 35 and 38 ° C.
- the intermediate layer can consist of a base material which is used for the production of rectal suppositories, preferably one or more hard fats (Adeps Solidus) according to the monograph of the European Pharmacopoeia.
- the intermediate layer can also be an oily solution, suspension or emulsion.
- the intermediate layer within the fabric can have a segmentation in that the upper and lower cover layers are connected to one another in this area by sealing.
- the intermediate layer can also contain at least one active pharmaceutical ingredient in dissolved or undissolved form.
- the solubility of the active pharmaceutical ingredient in the intermediate layer can be at least n times 10, preferably n times 10-100, where n represents the solubility of the outer layers.
- a process for the production of a flat system is claimed, wherein in a first process step an intermediate layer of a lipophilic pharmaceutical is applied to a water-soluble polymer layer Preparation applied in a thin layer and then covered with a second water-soluble polymer layer, after which in a further process step the upper and lower polymer layers are connected to one another in sections by heat sealing, the intermediate layer being displaced under the influence of mechanical pressure at the sealing points between the upper and lower polymer layers and and compartments which are completely enclosed by the sealed cover layers continue to form in the intermediate layer.
- the residual moisture in the water-soluble polymer films can be set to a value which improves the sealability, preferably 1-10% and particularly preferably 2-5% (m / m) water content. Furthermore, in the process according to the invention, the residual moisture in the water-soluble polymer films can be reduced by a drying process after the production of the flat capsules.
- the sealability of the water-soluble polymer films can also be ensured by plasticizing additives from the group of hydrophilic liquids, preferably from the group of polyhydric alcohols with 3 to 6 carbon atoms (C 3 -C 6 ), particularly preferably glycerol, 1, 2-propylene glycol , 1, 3-propylene glycol, 1, 3-butanediol, hexylene glycol or dipropylene glycol.
- plasticizing additives from the group of hydrophilic liquids, preferably from the group of polyhydric alcohols with 3 to 6 carbon atoms (C 3 -C 6 ), particularly preferably glycerol, 1, 2-propylene glycol , 1, 3-propylene glycol, 1, 3-butanediol, hexylene glycol or dipropylene glycol.
- the flat system according to the invention can contain one or two steroid hormones for hormone replacement therapy or for hormonal contraception.
- the steroid hormones can be levonorgestrel, gestodene, dienogest, de-soestrestr, 3-keto-desogestrel, norelgestromin, drospirenone, estradiol, ethyl tradiol, estradiol valerate, testosterone, testosterone undecanoate, testosterone enanthate, 1alpha-n-methyl ester, 7alpha-n-methyl ester fluorine-containing derivatives.
- an active ingredient from the group of organic nitrates used for the treatment of angina pectoris
- glycerol trinitrate or an active ingredient from the group of antiemetics, in particular 5-HT 3 receptor antagonists and particularly preferably from the group of Ondansetron, granistron, ramosetron, alosetron or their pharmaceutically acceptable salts.
- the flat system can also contain nicotine base or a pharmaceutically acceptable salt thereof. Both with organic nitrates and with nicotine, there is a need to make the active ingredient available in the bloodstream as quickly as possible via the oral mucosa. Active substances for the treatment of old age diseases, in particular Morbus Alzheimer's, Parkinson's disease and dementia diseases, as well as active substances for the treatment of severe mental illnesses such as schizophrenia or psychoses can be contained in the flat system according to the invention. These therapeutic fields are characterized in part by the fact that there is a reduced ability or willingness to swallow, which is why the use of a pharmaceutical form via the oral cavity is advantageous.
- the existing object can be achieved in that a flat structure with a multilayer structure is selected in which the function of water-soluble polymer film is carried out separately from the function of the active substance carrier in different layers, the active substance-containing layer as an intermediate layer with a smaller area than the total area of the system is carried out by leaving out the intermediate layer along the edge of the planar system.
- the water-soluble polymer films can surprisingly be processed so that they can be heat-sealed. This is surprisingly true even if there is a lipophilic oily or waxy intermediate layer between these layers prior to heat sealing.
- the invention makes it possible to embed an intermediate layer in the manner of an extremely flattened capsule in an envelope made of hydrophilic water-soluble polymer films.
- the intermediate layer can consist of a liquid, semi-solid or waxy solid preparation.
- the coating of water-soluble polymer films first dissolves.
- the intermediate layer then disintegrates either by melting or by dissolving in the saliva or by both processes simultaneously.
- the intermediate layer melts between 32 and 37 ° C. at the typical temperatures of the interior of the mouth.
- the intermediate layer is practically imperceptible to the sensor, the mouthfeel is significantly more pleasant than in the case of a permanent intermediate layer.
- the release of active substance from the lipophilic layer is facilitated or accelerated by its melting.
- waxy interlayers it should be un do not melt below 30 ° C to avoid melting during storage of the medicinal product.
- water-soluble polymer are suitable for the group of polyvinyl alcohols degree of hydrolysis of 75-99% (eg. B. Mowiol ® types), polyvinylpyrrolidone, hydrophilic cellulose derivatives such as hydroxypropylcellulose, Hydroxymethylpropylcellulsoe or carboxymethyl cellulose, pullulan, or maltose, hydrophilic starch derivatives such as carboxymethyl starch, alginates or gelatin and other polymers known in the prior art.
- polyvinyl alcohols degree of hydrolysis of 75-99% eg. B. Mowiol ® types
- polyvinylpyrrolidone polyvinylpyrrolidone
- hydrophilic cellulose derivatives such as hydroxypropylcellulose, Hydroxymethylpropylcellulsoe or carboxymethyl cellulose
- pullulan or maltose
- hydrophilic starch derivatives such as carboxymethyl starch, alginates or gelatin and other polymers known in the prior art.
- the formulation or the processing of the intermediate layer is essentially determined by three requirements: 1.
- the intermediate layer should dissolve quickly in the mouth by melting or dissolving in saliva or a combination of both. 2.
- the intermediate layer is coated directly onto a water-soluble polymer layer and, in terms of process engineering, should not require any solvents which can dissolve the polymer layer serving as the coating substrate.
- the intermediate layer must be thermoplastically deformable in order to be able to shrink back between the cover layers during heat sealing.
- a waxy, low-melting formulation is preferably suitable for the formulation of the lipophilic intermediate layer.
- rectal suppositories suppositories
- vaginal suppositories A selection of low-melting base materials with a melting point that can be selected within wide limits is, for. B. from the group of Softisan ® and Witepsol ® hard fats possible.
- Suitable carriers are also described in the monograph "Hard Fat" (Adeps Solidus) of the European Pharmacopoeia.
- oily, viscous solutions can be used as an intermediate layer.
- Suitable carriers are pharmaceutically customary oils and lipophilic liquids, which should preferably be largely tasteless, e.g.
- polymers from the group of polyacrylates eg Eudragit ® E 100 or Plastoid ® B
- polyvinylpyrrolidone Kollidon ® 25, 30, 90 or VA 64
- polyvinyl acetate e.g. Kollidon ® SR
- polyethylene glycol or lithium pophilic cellulose derivatives e.g. ethyl cellulose or cellulose acetate butyrate.
- z. B polyvinyl pyrrolidone (PVP) or its copolymers z. B. Kollidon ® 25, 30, 90 or VA 64, and polyethylene glycols (macrogols) with molecular weights greater than 2000 Da.
- the formulation of the intermediate layer can include, for example, additives from the groups of plasticizers, surfactants, solubilizers, penetration improvers, release agents, antioxidants, light and UV protection agents, pigments, dyes, taste corrections, organic or inorganic fillers, without any claim to completeness as well as fragrances are added.
- Solubilizers and penetration enhancers are particularly important:
- the flat capsules according to the invention have only a small internal volume, as a result of which the loadability with active substances is restricted. Furthermore, it can be advantageous if the active ingredients contained are taken up entirely or predominantly in the mouth via the mucous membrane, instead of only after swallowing through the gastrointestinal tract.
- the formulation of the intermediate layer should have the highest possible solvency for the intended active ingredient, for which purpose solubilizers can be used.
- the solubilizers must be selected in such a way that they do not jeopardize the integrity of the water-soluble cover layers by dissolving or dissolving or by greatly softening them.
- Suitable solubilizers are e.g. B. fatty acid esters of saturated fatty acids with chain lengths of 6 to 18 carbon atoms with mono- to trihydric aliphatic alcohols with 2 to 4 carbon atoms (e.g. ethyl oleate, propylene glycol monolaurate, glycerol monooleate), furthermore fatty alcohol ethers of fatty alcohols with 6 to 18 carbon atoms with polyethylene glycol (e.g. BRIJ ® products), fatty acid esters of fatty acids with 6 to 1 8 carbon atoms with polyethylene glycol (e.g.
- esters of fatty alcohols with 6 to 1 8 carbon atoms with carboxylic acids with 2 to 3 carbon atoms e.g. lauryl lactate or Lauryl acetate
- sorbitan fatty acid esters e.g. SPAN ® products
- sorbitan polyethylene glycol ether fatty acid esters e.g. TWEEN ® products
- citric acid esters e.g. triethyl citrate or acetyltributyl citrate
- Diethylene glycol monoethyl ether Transcutol ®
- propylene carbonate Solketal, Glycofurol, triacetin, cyclodextrins.
- compositions of the intermediate layer and the outer layers are advantageously chosen such that the solubility of the active substance in the intermediate layer is significantly greater in the intermediate layer than in the outer layers. This reduces possible undesired chemical decomposition reactions of the active substance after immigration into the outer layers.
- a water-soluble polymer film is first produced by coating a solution on a web-shaped support material and then drying it. Alternatively, the film can also be produced by a solvent-free hot melt process.
- the weight per unit area of the polymer layer is 25-200 g / m 2 , preferably 40-150 g / m 2 and particularly preferably 60-100 g / m 2 .
- An intermediate layer is applied from the side of the water-soluble polymer to this preliminary product (polymer film on a backing material, for example paper with a repellent coating).
- This is preferably a medium-viscosity, lipophilic liquid or the melt of a lipophilic mass.
- the application of the lipophilic liquid or mass can, for. B. with the help of a slot die, a doctor blade or roller applicator or a knife caster.
- the weight per unit area of this intermediate layer is 25-300 g / m 2 , preferably 30-200 g / m 2 and particularly preferably 40-150 g / m 2 .
- the intermediate layer is preferably not coated up to the edge of the underlying polymer layer, but at least 0.5 to 5 cm of space remain at the edge in order to prevent the intermediate layer from escaping at the edge in the subsequent method steps.
- the exposed surface of the intermediate layer after it has solidified again by cooling, is covered with a second water-soluble polymer layer, which as a rule has the same composition and method of manufacture as the first polymer layer lying at the bottom.
- the second water-soluble polymer layer is preferably first detached from its support material and laminated onto the intermediate layer as a single layer.
- the intermediate layer between the water-soluble polymer films is optionally first melted and then displaced by mechanical pressure on the parts to be sealed until the two water-soluble polymer films form a permanent bond with one another at these points by heat sealing.
- the sealability of the water-soluble polymer films can also be increased by plasticizing additives from the group of hydrophilic liquids, preferably by additives from the group of polyhydric alcohols with 3 to 6 carbon atoms (C 3 -C 6 ), particularly preferably glycerol, 1, 2-propylene glycol, 1, 3-propylene glycol, 1, 3-butanediol, hexylene glycol or dipropylene glycol.
- plasticizing additives from the group of hydrophilic liquids preferably by additives from the group of polyhydric alcohols with 3 to 6 carbon atoms (C 3 -C 6 ), particularly preferably glycerol, 1, 2-propylene glycol, 1, 3-propylene glycol, 1, 3-butanediol, hexylene glycol or dipropylene glycol.
- the upper and the lower polymer layer are sealed together along an intended contour line in such a way that a quantity of the lipophilic intermediate layer defined over the surface is completely enclosed in the manner of a single dose.
- the individual doses are formed, which is why the sealing mask used should have corresponding dimensional accuracies of plus or minus 5% or better in order to be able to comply with the pharmaceutically required dosage accuracies.
- the fabric is mechanically cut or punched along the sealed seams and divided into individual shapes or groups of individual shapes.
- the remaining web widths of the sealed edge areas of the flat structures should be kept as small as possible, since in these areas the water-soluble polymer films of the upper and lower cover layers together form a particularly thick zone, which allows the slowest dissolution rate in the mouth and a negative effect on the mouthfeel to be expected ,
- the width of the sealed seam should be 0.3 to 3 mm, preferably 0.5 to 2 mm and particularly preferably 0.75 to 1.5 mm. Description of the pictures:
- FIG. A1 schematically shows a flat system in cross section: an upper cover layer (1), together with a lower cover layer (2), encloses an inner intermediate layer (3).
- the two outer layers have a flat cavity, while in FIG. A2 the cavity for receiving the intermediate layer is only present in one of the two cover layers.
- the cover layers (1) and (2) can be of identical or different nature.
- Figure A3 a flat system with two separate chambers (3 and 4) is shown, which is formed with the help of a further cover layer (5).
- FIG. B shows a flat intermediate product after the heat-sealing step has taken place, in which case there may be several sections of the intermediate layer containing the active substance that are separate from one another, both longitudinally and transversely, which are converted into the end products in further process steps by cutting or punching
- Figures C1 to C5 show different embodiments of the fabrics according to the invention in a top view. They essentially serve to illustrate the possible embodiments. While the structures C2 and C3 are of greater visual acceptance by the consumers, the structures C1, C4 and C5 have a higher degree of utilization of the flat intermediate product with less waste production, although this is an active substance-free waste. Compared to FIG. C4, FIG. C5 illustrates the possibility that the contour line of the inner active substance-containing intermediate layer does not follow the outer contour line of the fabric got to.
- FIG. D shows an example of a flat structure with several active ingredient-containing sections (3).
- This product is a multi-dose structure that can be divided into different single doses.
- Figures E 1 to E4 illustrate a method step of heat sealing according to the invention.
- the laminate consisting of an upper (1) and a lower (2) cover layer with an inner intermediate layer (3) on a web-shaped carrier material (6) is pressed against a counterpressure surface (8) belonging to the sealing station by an embossing heat sealing tool (7). pressed, whereby either only the sealing tool or else the sealing tool and counter-pressure plate are heated.
- This method step can also be carried out with a counterpressure plate which has a flat cavity, as a result of which an approximately symmetrical shape of the flat system according to the invention is produced in cross section.
- a counterpressure plate which has a flat cavity
- FIG. E4 curves are provided at the points on the sealing mask (7) marked with arrows, which lead to a reduction in the mechanical deformation stress on the cover layer (1) and thus reduce the risk of cracks or leaks at the sealing seam.
- This technique can also be applied analogously to the bilateral shaping according to FIG. E3.
- Figures E1 to E4 illustrate the relevant method step on a flat bed sealing punch for a clocked mode of operation in which the laminate web is stopped during the processing step.
- this process step can also be carried out on rotary systems with appropriately contoured sealing or embossing rollers and with the laminate web running continuously.
- Softisan 100 is heated until it melts on the water bath. Using a Pasteur pipette, Softisan 100 is applied evenly to the entire EclipseTM Peppermint leaflet (3x2crn). After solidification of the hard fat occurs, another EclipseTM Peppermint leaflet (3x2cm) is applied precisely to the lipophilic layer. The three-layer intermediate product is then sealed from all four sides with the aid of a sealing tongs heated to approx. 1 60 ° C for approx. 5 seconds.
- Softisan 1 00 is heated to a clear melt on a water bath. Using a Pasteur pipette, Softisan 100 is applied evenly to the entire Eclipse TM Peppermint leaflet (3x2cm). After the hard fat solidifies, another EclipseTM Peppermint leaflet (3x2cm) is applied precisely to the lipophilic layer. A second layer of hard fat is applied, which in turn is covered with an Eclipse TM Peppermint leaflet (3x2cm) to ensure a perfect fit. The five-layer intermediate product is then sealed from all four sides with the aid of sealing tongs heated to approx. 1 60 ° C. for approx. 8 seconds.
- Example 3 Three-layer flat capsule with an oily intermediate layer Materials: Eclipse TM Peppermint papers (3x2cm) (Wrigley) Viscose paraffin disposable Pasteur pipette sealing pliers Version:
- Viscose paraffin is applied evenly to the entire EclipseTM Peppermint leaflet (3x2cm) using a Pasteur pipette. Another EclipseTM Peppermint leaflet (3x2cm) is applied precisely to the lipophilic layer.
- the three-layer intermediate product is then sealed from all four sides with the aid of sealing tongs heated to approx. 160 ° C for approx. 5 seconds.
- Determinations and calculations used in Examples 1-3 To determine the basis weight (FG), the multilayer products produced are weighed individually and the respective areas are determined. The weight of 10 Eclipse TM Peppermint papers is determined and the mean is calculated. The dimensions are determined accordingly and the area is calculated. The conversion of the units is taken into account in the calculation formula.
- the weight per unit area of the softisan layer in example 1 was 132 g / m 2 .
- the weight per unit area of the oily layer in Example 3 was 80 g / m 2 .
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Zoology (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US54139604P | 2004-02-03 | 2004-02-03 | |
DE102004017030A DE102004017030A1 (en) | 2004-04-02 | 2004-04-02 | Flat system for use in the oral cavity, e.g. for transmucosal drug delivery, comprises an intermediate, active agent-containing layer sealed between two covering layers of higher surface area |
PCT/EP2005/001076 WO2005074882A2 (en) | 2004-02-03 | 2005-02-03 | Flat system for using in the oral cavity |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1711160A2 true EP1711160A2 (en) | 2006-10-18 |
Family
ID=35034148
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP05707164A Withdrawn EP1711160A2 (en) | 2004-02-03 | 2005-02-03 | Flat system for using in the oral cavity |
Country Status (11)
Country | Link |
---|---|
US (1) | US20070298084A1 (en) |
EP (1) | EP1711160A2 (en) |
JP (1) | JP2007520517A (en) |
KR (1) | KR20060123610A (en) |
CN (1) | CN1913870A (en) |
AU (1) | AU2005210123A1 (en) |
BR (1) | BRPI0507389A (en) |
CA (1) | CA2554892A1 (en) |
DE (1) | DE102004017030A1 (en) |
NO (1) | NO20063915L (en) |
WO (1) | WO2005074882A2 (en) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI394593B (en) * | 2007-03-30 | 2013-05-01 | Lintec Corp | Methods of making pharmaceuticals for oral administration |
RU2456981C2 (en) * | 2007-03-30 | 2012-07-27 | ЛИНТЕК Корпорейшн | Oral film drug and method for preparing it |
EP2206519B1 (en) * | 2007-09-28 | 2012-08-01 | Lintec Corporation | Medicinal preparation for oral administration |
JP2011143153A (en) * | 2010-01-18 | 2011-07-28 | Tsukioka:Kk | Film pack |
JP5875246B2 (en) * | 2010-12-10 | 2016-03-02 | 日東電工株式会社 | Sheet-form preparation and method for producing sheet-form preparation |
WO2015028670A2 (en) * | 2013-09-01 | 2015-03-05 | Danmarks Tekniske Universitet | Method for the fabrication of multi-layered micro-containers for drug delivery |
DE102017127434A1 (en) * | 2017-11-21 | 2019-05-23 | Lts Lohmann Therapie-Systeme Ag | Pocket-shaped oral-release films with high drug loading |
DE102019100483A1 (en) * | 2019-01-10 | 2020-07-16 | Lts Lohmann Therapie-Systeme Ag | Oral thin film |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH624846A5 (en) * | 1975-12-15 | 1981-08-31 | Hoffmann La Roche | Solid pharmaceutical unit dose form and process and apparatus for producing it |
ZA767136B (en) * | 1975-12-15 | 1977-10-26 | Hoffmann La Roche | Novel dosage form |
DE19652257A1 (en) * | 1996-12-16 | 1998-06-18 | Lohmann Therapie Syst Lts | Individually dosed, film-like dosage form that quickly disintegrates on contact with liquid and contains active ingredients and especially flavorings |
DE19800682B4 (en) * | 1998-01-10 | 2004-07-08 | Lts Lohmann Therapie-Systeme Ag | Process for producing a primary packaging for film or wafer-shaped administration forms |
GB2338896B (en) * | 1998-07-02 | 2003-05-21 | Reckitt & Colmann Prod Ltd | Chewable Capsules |
DE10008165A1 (en) * | 2000-02-23 | 2001-08-30 | Lohmann Therapie Syst Lts | Packaging of sheet-like objects with improved tear properties |
DE10102818A1 (en) * | 2001-01-23 | 2002-08-08 | Lohmann Therapie Syst Lts | Primary packaging unit for several isolated film platelets as dosage forms |
DE10107659B4 (en) * | 2001-02-19 | 2008-03-13 | Lts Lohmann Therapie-Systeme Ag | Mucoadhesive disintegratable drug preparation for drug administration in veterinary and human medicine |
DE10143120A1 (en) * | 2001-09-03 | 2003-03-27 | Lohmann Therapie Syst Lts | Container with sliding lid |
DE10159746B4 (en) * | 2001-12-05 | 2006-05-18 | Lts Lohmann Therapie-Systeme Ag | Dispensing device for sheet-like dosage forms |
-
2004
- 2004-04-02 DE DE102004017030A patent/DE102004017030A1/en not_active Withdrawn
-
2005
- 2005-02-03 EP EP05707164A patent/EP1711160A2/en not_active Withdrawn
- 2005-02-03 US US10/588,222 patent/US20070298084A1/en not_active Abandoned
- 2005-02-03 AU AU2005210123A patent/AU2005210123A1/en not_active Abandoned
- 2005-02-03 CA CA002554892A patent/CA2554892A1/en not_active Abandoned
- 2005-02-03 JP JP2006551801A patent/JP2007520517A/en not_active Revoked
- 2005-02-03 KR KR1020067017854A patent/KR20060123610A/en not_active Application Discontinuation
- 2005-02-03 CN CNA2005800039706A patent/CN1913870A/en active Pending
- 2005-02-03 WO PCT/EP2005/001076 patent/WO2005074882A2/en active Application Filing
- 2005-02-03 BR BRPI0507389-8A patent/BRPI0507389A/en not_active IP Right Cessation
-
2006
- 2006-09-01 NO NO20063915A patent/NO20063915L/en not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO2005074882A2 * |
Also Published As
Publication number | Publication date |
---|---|
NO20063915L (en) | 2006-09-01 |
JP2007520517A (en) | 2007-07-26 |
KR20060123610A (en) | 2006-12-01 |
CN1913870A (en) | 2007-02-14 |
CA2554892A1 (en) | 2005-08-18 |
BRPI0507389A (en) | 2007-07-10 |
DE102004017030A1 (en) | 2005-10-20 |
WO2005074882A3 (en) | 2006-06-15 |
US20070298084A1 (en) | 2007-12-27 |
AU2005210123A1 (en) | 2005-08-18 |
WO2005074882A2 (en) | 2005-08-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0949925B1 (en) | Flat medicament preparation for the application and release of buprenorphine or a pharmacologically comparable substance in the buccal cavity, and method of producing the same | |
EP0936905B1 (en) | Immediate wettability water soluble film or water soluble layer for oral application | |
WO2005074882A2 (en) | Flat system for using in the oral cavity | |
DE69119598T2 (en) | TRANSDERMIC DEVICE | |
DE19715794C1 (en) | Laminar dosage form and process for its preparation | |
DE2432925A1 (en) | Medicaments in form of foils - prepd. by incorporating a drug in a soluble foil-forming material | |
EP2273987B1 (en) | Film-shaped preparation comprising oily substances for oral administration | |
DE2932615A1 (en) | SOLID PHARMACEUTICAL DOSAGE UNIT | |
EP1560564B1 (en) | Multi-layer transmucosal therapeutic system | |
EP4076392A1 (en) | Soluble rear layer for otf | |
WO2020144345A1 (en) | Oral thin film | |
EP2632443A2 (en) | Preparation of orodispersible films | |
WO2004052347A1 (en) | Transmucosal and transdermal medicaments with an improved active ingredient absorption | |
DE102014000200A1 (en) | Transdermal Therapeutic System | |
WO2016058790A1 (en) | Oromucosal film preparation | |
EP3829550B1 (en) | Transdermal therapeutic system for dispensing scopolamine without a membrane | |
EP2381933A1 (en) | Patch production technology | |
WO2020259765A1 (en) | Method for producing active agent administering systems by means of pad printing processes | |
EP4277595A1 (en) | Multi-layer oral thin film | |
WO2023094638A1 (en) | Application aid for an oral thin film | |
WO2014090981A1 (en) | Topical drug for treating aphthae | |
EP3743050A1 (en) | Multi-layer oral thin film | |
DE102019201431A1 (en) | Transdermal therapeutic system (TTS) with solids reservoir | |
ZA200607349B (en) | Flat system for using in the oral cavity | |
DE19736315A1 (en) | Active agent containing device, for dermal use |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20060725 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR |
|
AX | Request for extension of the european patent |
Extension state: AL BA HR LV MK YU |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: GUTSMUTHS, BABETT Inventor name: BRACHT, STEFAN |
|
RAX | Requested extension states of the european patent have changed |
Extension state: YU Payment date: 20060725 Extension state: MK Payment date: 20060725 Extension state: LV Payment date: 20061215 Extension state: HR Payment date: 20060725 Extension state: BA Payment date: 20060725 Extension state: AL Payment date: 20060725 |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: BAYER SCHERING PHARMA AG |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: BAYER SCHERING PHARMA AKTIENGESELLSCHAFT |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: BAYER PHARMA AKTIENGESELLSCHAFT |
|
17Q | First examination report despatched |
Effective date: 20120430 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20120918 |