EP4199920A1 - Formulations de film orodispersible comprenant des doses élevées d'élétriptan - Google Patents
Formulations de film orodispersible comprenant des doses élevées d'élétriptanInfo
- Publication number
- EP4199920A1 EP4199920A1 EP21858726.9A EP21858726A EP4199920A1 EP 4199920 A1 EP4199920 A1 EP 4199920A1 EP 21858726 A EP21858726 A EP 21858726A EP 4199920 A1 EP4199920 A1 EP 4199920A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- pharmaceutically acceptable
- formulation according
- orodispersible
- orodispersible film
- film formulation
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 65
- 238000009472 formulation Methods 0.000 title claims abstract description 51
- 229960002472 eletriptan Drugs 0.000 title claims abstract description 46
- OTLDLQZJRFYOJR-LJQANCHMSA-N eletriptan Chemical compound CN1CCC[C@@H]1CC1=CN=C2[C]1C=C(CCS(=O)(=O)C=1C=CC=CC=1)C=C2 OTLDLQZJRFYOJR-LJQANCHMSA-N 0.000 title claims abstract 13
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 206010027599 migraine Diseases 0.000 claims abstract description 20
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 239000000796 flavoring agent Substances 0.000 claims description 14
- 239000004373 Pullulan Substances 0.000 claims description 10
- 229920001218 Pullulan Polymers 0.000 claims description 10
- 235000019634 flavors Nutrition 0.000 claims description 10
- 235000019423 pullulan Nutrition 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 9
- 229920000881 Modified starch Polymers 0.000 claims description 8
- 239000004368 Modified starch Substances 0.000 claims description 8
- 235000019426 modified starch Nutrition 0.000 claims description 8
- 206010019233 Headaches Diseases 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical group O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003086 colorant Substances 0.000 claims description 6
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 231100000869 headache Toxicity 0.000 claims description 6
- 229920000642 polymer Polymers 0.000 claims description 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- 239000004376 Sucralose Substances 0.000 claims description 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 230000002209 hydrophobic effect Effects 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000004014 plasticizer Substances 0.000 claims description 5
- 235000019408 sucralose Nutrition 0.000 claims description 5
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 229930091371 Fructose Natural products 0.000 claims description 4
- 239000005715 Fructose Substances 0.000 claims description 4
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical class NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 4
- 238000000576 coating method Methods 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 235000013355 food flavoring agent Nutrition 0.000 claims description 4
- 235000019264 food flavour enhancer Nutrition 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 239000003921 oil Substances 0.000 claims description 4
- 235000019198 oils Nutrition 0.000 claims description 4
- -1 pamoate Chemical class 0.000 claims description 4
- 235000010987 pectin Nutrition 0.000 claims description 4
- 239000001814 pectin Substances 0.000 claims description 4
- 229920001277 pectin Polymers 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 235000010356 sorbitol Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 4
- 206010009094 Chronic paroxysmal hemicrania Diseases 0.000 claims description 3
- 208000006561 Cluster Headache Diseases 0.000 claims description 3
- 239000004097 EU approved flavor enhancer Substances 0.000 claims description 3
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 3
- 240000009088 Fragaria x ananassa Species 0.000 claims description 3
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 238000005520 cutting process Methods 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- 235000011187 glycerol Nutrition 0.000 claims description 3
- 238000004806 packaging method and process Methods 0.000 claims description 3
- 208000007777 paroxysmal Hemicrania Diseases 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 3
- 229940068968 polysorbate 80 Drugs 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 239000004408 titanium dioxide Substances 0.000 claims description 3
- 208000019553 vascular disease Diseases 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical class CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 235000019489 Almond oil Nutrition 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 239000004475 Arginine Chemical class 0.000 claims description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical class [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical class [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical class [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical class [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- 235000005979 Citrus limon Nutrition 0.000 claims description 2
- 244000131522 Citrus pyriformis Species 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 239000001329 FEMA 3811 Substances 0.000 claims description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical class [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 239000004471 Glycine Chemical class 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical class NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical class OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical class CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 244000147568 Laurus nobilis Species 0.000 claims description 2
- 235000017858 Laurus nobilis Nutrition 0.000 claims description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Chemical class NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
- 239000004472 Lysine Chemical class 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical class [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical class [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical class OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical class [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 235000005212 Terminalia tomentosa Nutrition 0.000 claims description 2
- 240000007313 Tilia cordata Species 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical class [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 claims description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 claims description 2
- 240000006365 Vitis vinifera Species 0.000 claims description 2
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 2
- 239000000619 acesulfame-K Substances 0.000 claims description 2
- 239000008168 almond oil Substances 0.000 claims description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical class [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052782 aluminium Inorganic materials 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Chemical class OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 229940009098 aspartate Drugs 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical class [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical class OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000011575 calcium Chemical class 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 235000010980 cellulose Nutrition 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000008370 chocolate flavor Substances 0.000 claims description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical class C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 2
- 229960001231 choline Drugs 0.000 claims description 2
- 239000003240 coconut oil Substances 0.000 claims description 2
- 235000019864 coconut oil Nutrition 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 239000008121 dextrose Substances 0.000 claims description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical class CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical class OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims description 2
- 229950010286 diolamine Drugs 0.000 claims description 2
- 235000013399 edible fruits Nutrition 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- 235000008617 food flavour solvent Nutrition 0.000 claims description 2
- 235000021255 galacto-oligosaccharides Nutrition 0.000 claims description 2
- 150000003271 galactooligosaccharides Chemical class 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 239000001087 glyceryl triacetate Substances 0.000 claims description 2
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 2
- 229960002449 glycine Drugs 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical class OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 2
- ILVUABTVETXVMV-UHFFFAOYSA-N hydron;bromide;iodide Chemical class Br.I ILVUABTVETXVMV-UHFFFAOYSA-N 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 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 2
- 235000021579 juice concentrates Nutrition 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims description 2
- 229960003646 lysine Drugs 0.000 claims description 2
- 239000011777 magnesium Chemical class 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 2
- 239000001095 magnesium carbonate Substances 0.000 claims description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
- 229940091250 magnesium supplement Drugs 0.000 claims description 2
- 229940049920 malate Drugs 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical class OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000000845 maltitol Substances 0.000 claims description 2
- 235000010449 maltitol Nutrition 0.000 claims description 2
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 2
- 229940035436 maltitol Drugs 0.000 claims description 2
- 229960003194 meglumine Drugs 0.000 claims description 2
- 239000001525 mentha piperita l. herb oil Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical class COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 239000008368 mint flavor Substances 0.000 claims description 2
- 125000005487 naphthalate group Chemical class 0.000 claims description 2
- ITVGXXMINPYUHD-CUVHLRMHSA-N neohesperidin dihydrochalcone Chemical group C1=C(O)C(OC)=CC=C1CCC(=O)C(C(=C1)O)=C(O)C=C1O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 ITVGXXMINPYUHD-CUVHLRMHSA-N 0.000 claims description 2
- 229940089953 neohesperidin dihydrochalcone Drugs 0.000 claims description 2
- 235000010434 neohesperidine DC Nutrition 0.000 claims description 2
- 239000011664 nicotinic acid Chemical class 0.000 claims description 2
- 235000001968 nicotinic acid Nutrition 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- 239000007968 orange flavor Substances 0.000 claims description 2
- 235000019371 penicillin G benzathine Nutrition 0.000 claims description 2
- 235000019477 peppermint oil Nutrition 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical class [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 150000003021 phthalic acid derivatives Chemical class 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 239000004584 polyacrylic acid Substances 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 235000019204 saccharin Nutrition 0.000 claims description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 2
- 229940081974 saccharin Drugs 0.000 claims description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 2
- 239000010670 sage oil Substances 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 239000011734 sodium Chemical class 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical class [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000000454 talc Substances 0.000 claims description 2
- 229910052623 talc Inorganic materials 0.000 claims description 2
- 239000010678 thyme oil Substances 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 229960002622 triacetin Drugs 0.000 claims description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 2
- 229960000281 trometamol Drugs 0.000 claims description 2
- 239000008371 vanilla flavor Substances 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 239000011701 zinc Chemical class 0.000 claims description 2
- 229910052725 zinc Chemical class 0.000 claims description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 239000008180 pharmaceutical surfactant Substances 0.000 claims 1
- 239000010408 film Substances 0.000 description 99
- PWVXXGRKLHYWKM-LJQANCHMSA-N eletriptan Chemical compound CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2CCS(=O)(=O)C1=CC=CC=C1 PWVXXGRKLHYWKM-LJQANCHMSA-N 0.000 description 36
- 239000008194 pharmaceutical composition Substances 0.000 description 33
- 238000000034 method Methods 0.000 description 15
- 229940079593 drug Drugs 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 239000002552 dosage form Substances 0.000 description 11
- 239000003826 tablet Substances 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 229960003708 sumatriptan Drugs 0.000 description 4
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229960003470 eletriptan hydrobromide Drugs 0.000 description 3
- UTINOWOSWSPFLJ-FSRHSHDFSA-N eletriptan hydrobromide Chemical compound Br.CN1CCC[C@@H]1CC(C1=C2)=CNC1=CC=C2CCS(=O)(=O)C1=CC=CC=C1 UTINOWOSWSPFLJ-FSRHSHDFSA-N 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 239000006191 orally-disintegrating tablet Substances 0.000 description 3
- 210000003296 saliva Anatomy 0.000 description 3
- 238000000807 solvent casting Methods 0.000 description 3
- 230000009747 swallowing Effects 0.000 description 3
- 235000019640 taste Nutrition 0.000 description 3
- 239000008351 acetate buffer Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229940124433 antimigraine drug Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound 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 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960004943 ergotamine Drugs 0.000 description 2
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 2
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 2
- 229960005150 glycerol Drugs 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229940070979 relpax Drugs 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- 102000035038 5-HT1 receptors Human genes 0.000 description 1
- 108091005478 5-HT1 receptors Proteins 0.000 description 1
- VCCNKWWXYVWTLT-CYZBKYQRSA-N 7-[(2s,3r,4s,5s,6r)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-one Chemical compound C1=C(O)C(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 VCCNKWWXYVWTLT-CYZBKYQRSA-N 0.000 description 1
- WKEMJKQOLOHJLZ-UHFFFAOYSA-N Almogran Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CS(=O)(=O)N1CCCC1 WKEMJKQOLOHJLZ-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 229920002799 BoPET Polymers 0.000 description 1
- 206010064012 Central pain syndrome Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010054956 Phonophobia Diseases 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- 229960002133 almotriptan Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 208000018912 cluster headache syndrome Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229960001903 ergotamine tartrate Drugs 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229960002284 frovatriptan Drugs 0.000 description 1
- SIBNYOSJIXCDRI-SECBINFHSA-N frovatriptan Chemical compound C1=C(C(N)=O)[CH]C2=C(C[C@H](NC)CC3)C3=NC2=C1 SIBNYOSJIXCDRI-SECBINFHSA-N 0.000 description 1
- 238000009474 hot melt extrusion Methods 0.000 description 1
- GVLGAFRNYJVHBC-UHFFFAOYSA-N hydrate;hydrobromide Chemical group O.Br GVLGAFRNYJVHBC-UHFFFAOYSA-N 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 238000007561 laser diffraction method Methods 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229960005254 naratriptan Drugs 0.000 description 1
- UNHGSHHVDNGCFN-UHFFFAOYSA-N naratriptan Chemical compound C=12[CH]C(CCS(=O)(=O)NC)=CC=C2N=CC=1C1CCN(C)CC1 UNHGSHHVDNGCFN-UHFFFAOYSA-N 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 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
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 229960000425 rizatriptan Drugs 0.000 description 1
- TXHZXHICDBAVJW-UHFFFAOYSA-N rizatriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1CN1C=NC=N1 TXHZXHICDBAVJW-UHFFFAOYSA-N 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- ZISSAWUMDACLOM-UHFFFAOYSA-N triptane Chemical group CC(C)C(C)(C)C ZISSAWUMDACLOM-UHFFFAOYSA-N 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000009736 wetting 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
- A61K9/0012—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
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- 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
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- 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
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
Definitions
- the present invention relates to orodispersible film formulations comprising high amounts of eletriptan or pharmaceutically acceptable salt thereof, and use of these formulations in the treatment of migraine.
- Migraine is a very common disease that progresses with an average of two attacks per month, is usually one-sided, worsens with physical activity and is characterized by attacks associated with moderate-to- severe throbbing headache, nausea and/or vomiting, photophobia and phonophobia.
- the vast majority of people having migraine use an antimigraine drug as an acute treatment method.
- the object of the treatment of acute migraine attack is to quickly alleviate the pain and associated symptoms, and to prevent the recurrence of the pain.
- Acute treatment is gaining importance since in migraine attacks the pain that cannot be relieved within 60 - 120 minutes might cause central sensitization and allodynia (Burslein R, Jakubowski M, Rauch SD. The science of migraine. J Vestib Res 2011;21(6):305-14).
- Non-specific drugs include simple analgesics, combination analgesics (analgesics comprising caffeine or codeine combinations), NSAIDs, neuroleptic drugs, antiemetic drugs, steroids, and opioids.
- Specific drugs are divided into two groups, namely drugs belonging to ergo group (drugs containing ergotamine tartrate) and belonging to trip tan group.
- Triptans which are the most recently discovered molecular group of migraine -specific drugs, are free from the side effects of ergotamine narrowing the peripheral vessels, as they have agonistic actions selective to 5-HT IB/ ID receptors. They also have very high absorption rates compared to ergotamine, which has very low absorption rates. This creates an opportunity to easily administer effective doses.
- Eletriptan is a serotonin agonist used in the treatment of acute migraine headache. It is a member of a group of anti-migraine drugs comprising almotriptan, frovatriptan, naratriptan, rizatriptan, and sumatriptan which are commonly called “triptans”. It is a selective 5-HT1 receptor agonist with a structure as shown in the figure below; its chemical name is (R)-3-(l-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulfonyl)ethyl]- IH-indole.
- Eletriptan was licensed by the FDA in 2002 in oral tablet form in 20 and 40 mg doses with the trade name Relpax®, for use in the treatment of migraine with or without aura.
- Eletriptan was first disclosed in patent document No. EP0592438 Bl for use in the treatment of hypertension, depression, anxiety, eating disorders, obesity, substance abuse, cluster headache, migraine, pain and chronic paroxysmal hemicrania, and vascular disorders associated with headache.
- patent document No. EP0776323 Bl discloses the hydrobromide salt of eletriptan and processes for obtaining hydrobromide salt
- patent document No. EPl 135381 Bl discloses the hydrobromide monohydrate form of eletriptan. The technical problem to be solved by the invention
- the tablet In conventional tablet or capsule dosage forms, the tablet must be disintegrated or dissolved before the drug enters into the systemic circulation and is absorbed there, and the therapeutic effect occurs. Furthermore, swallowing the tablet or capsule dosage forms comprising high doses of active ingredients poses a major problem for pediatric, geriatric or mentally retarded patients. Liquid dosage forms are not suitable dosage forms since they have a short half-life despite exhibiting a rapid action.
- Solid oral dosage forms such as tablets and capsules do not provide sufficient success in the treatment of diseases such as migraine, where the action must be seen quickly (for example, in the first half hour or less).
- Drugs in the form of a orodispersible film are thin films of hydrophilic polymers that resembles postage stamps in size, shape and thickness, and dissolve quickly on the tongue or on the bottom thereof.
- the film wet with saliva disintegrates within seconds and releases the drug content.
- Orodispersible films are one of the dosage forms that are gaining popularity and that have been studied extensively in the literature after orally disintegrating tablets.
- the use of orodispersible films is gradually increasing with many advantages such as;
- dosage forms of the orodispersible film have very low capacity to carry active ingredients.
- pharmaceutical formulations comprising high doses of eletriptan or a pharmaceutically acceptable salt thereof, which provide a rapid and efficient treatment onset and increase the bioavailability of eletriptan especially in the treatment of migraine attacks.
- the present invention discloses pharmaceutical formulations in the form of orodispersible film, comprising high doses of eletriptan or pharmaceutically acceptable salt thereof, production methods of these formulations, and their use in the treatment of migraine attacks.
- the present invention relates to orodispersible film formulations, comprising high doses of eletriptan or pharmaceutically acceptable salt thereof.
- the present invention relates to pharmaceutical formulations in the form of orodispersible film, comprising as a high dose, more than 30% by weight of the film eletriptan or a pharmaceutically acceptable salt thereof based on the film weight.
- the present invention relates to pharmaceutical formulations in the form of orodispersible film, comprising as a high dose, more than 35% by weight of the film eletriptan or a pharmaceutically acceptable salt thereof based on the film weight.
- Another object of the present invention is to provide a method for producing pharmaceutical formulations in the form of orodispersible film, comprising high doses of eletriptan or a pharmaceutically acceptable salt thereof which has a pleasant taste and dissolve rapidly.
- orodispersible film is meant a single - or multi-layer thin film that is administered orally to the oral mucosa and disintegrates rapidly in the patient's oral cavity.
- the active ingredient carried in the orodispersible film disintegrates in the oral mucosa and is absorbed therefrom.
- compositions in the form of orodispersible film according to the present invention comprise high doses of eletriptan or a pharmaceutically acceptable salt thereof.
- eletriptan in pharmaceutical formulations in the form of a orodispersible film according to the present invention, eletriptan can be used in free form or in the form of a pharmaceutically acceptable salt which may be selected from salts of acetate, aspartate, benzoate, besylate, bicarbonate, carbonate, bisulfate, sulfate, borate, citrate, formate, fumarate, hydrochloride, chloride, hydrobromide, hydrobromide iodide, lactate, malate, maleate, malonate, mesylate, methylsulfate, naphthalate, nicotinate, nitrate, oxalate, pamoate, phosphate, hydrogen phosphate, dihydrogen phosphate, stearate, succinate, tosylate, trifluoroacetate, aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, ly
- compositions in the form of orodispersible film according to the present invention may comprise 5 - 300 mg, preferably 10 - 150 mg of eletriptan or pharmaceutically acceptable salt thereof as active ingredient.
- Preferred orodispersible film formulations of the invention may comprise preferably 20 mg and 40 mg or equivalent amounts of eletriptan or pharmaceutically acceptable salt thereof.
- the orodispersible formulations in the form of film of the present invention comprise at least one pharmaceutically acceptable film former.
- the physical characteristics and durability of the resulting film vary greatly depending on the type and amount of polymer used as film former.
- the polymer used should be non-irritating and non-toxic, have good wetting properties, and be cost-effective.
- properties of the resulting product such as disintegration time, drug loading capacity, mechanical resistance and brittleness can be controlled. Therefore, the choice of polymer is a critical parameter for orodispersible films.
- the film formers that can be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention can be selected from pullulan, starch, modified starch, sodium alginate, pectin, low-viscosity pectin, gelatin, polymerized resin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, polyvinyl alcohol, polyethylene oxide, polyvinyl pyrrolidone, polyacrylic acid, or combinations thereof.
- the weight of the film former to be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention may be in the range of 20-60% by weight, based on the total film weight of the present composition.
- the film formers used in the present invention comprise of a combination of modified starch and pullulan.
- the ratio of modified starch to pullulan used in the present invention can be 1:7 - 1:1, preferably 1:5 - 1:1.
- compositions in the form of orodispersible film according to the present invention may comprise eletriptan or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient together with at least one pharmaceutically acceptable film former.
- Pharmaceutically acceptable excipients that can be used according to the present invention may be selected from plasticizers, surfactants, colorants, flavoring agents, sweeteners, fillers, flavor enhancers, solvents, or combinations thereof.
- Plasticizers that can be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention may be selected from propylene glycol, polyethylene glycol, low molecular weight polyethylene glycol, glycerin, phthalic acid esters, sorbitol, maltitol, starch syrup, triacetin, or combinations thereof.
- the amount of plasticizer used in the present invention can be in the range of 0.5 - 20% by weight, based on the total film weight.
- Surfactants that can be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention may be selected from polysorbate 80, sodium lauryl sulfate, poloxamer, benzalkonium chloride, lecithin, or combinations thereof.
- Colorants that can be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention may be selected from titanium dioxide, FD&C approved colorants, silicon dioxide, natural juice concentrates, or combinations thereof.
- Flavoring agents that can be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention may be selected from resins, extracts and/or oils obtained from fruits such as peppermint oil, thyme oil, laurel oil, coconut oil, sage oil, almond oil, and synthetic flavors such as mint flavor, lemon flavor, orange flavor, grape flavor, linden flavor, strawberry flavor, chocolate flavor, vanilla flavor.
- Natural or artificial sweeteners can be used to increase patient compliance and to mask bitter taste in orodispersible film formulations.
- Sweeteners that can be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention may be selected from glucose, sucrose, dextrose, fructose, maltose, aspartame, saccharin, sucralose, acesulfame-K, or combinations thereof.
- the amount of sweetener used in the present invention is 2 - 10% (w/w) by weight, based on the total film weight.
- Fillers that can be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention may be selected from pullulan, mannitol, microcrystalline cellulose, cellulose polymers, magnesium carbonate, calcium carbonate, silicate, talc, or combinations thereof.
- Solvents that can be used in the pharmaceutical formulations in the form of orodispersible film according to the present invention may be selected from ethanol, deionized water, isopropanol, methylene chloride, toluene, or combinations thereof.
- Another object of the present invention is to describe a method for producing pharmaceutical formulations in the form of orodispersible film, comprising high doses of eletriptan or a pharmaceutically acceptable salt thereof.
- compositions in the form of orodispersible film according to the present invention can be obtained by a production method that may be selected from solvent casting method, hot melt extrusion method, semi-solid molding method, rolling method, solid dispersion methods.
- a production method that may be selected from solvent casting method, hot melt extrusion method, semi-solid molding method, rolling method, solid dispersion methods.
- orodispersible film according to the present invention is produced using the solvent casting method.
- Solvent casting technique is frequently preferred since it is an easy technique in the production of orodispersible films, is not expensive, does not require high temperatures and special requirements.
- this method after the aqueous or hydroalcoholic solution of the active ingredients and auxiliary substances is prepared, air bubbles are removed by means of vacuum. Then it is poured onto the surface as a flat layer, dried and cut into desired dimensions to obtain a film with a uniform thickness.
- Pharmaceutical formulations in the form of orodispersible film according to the present invention can be produced by a production method according to the following steps;
- the resulting mixture can preferably be subjected to a defoaming process before being poured onto a hydrophobic film.
- compositions in the form of orodispersible film according to the present invention can be produced by a production method comprising the following steps;
- At least one pharmaceutically acceptable excipient is slowly added to the mixture and mixed continuously,
- the hydrophobic film used in the production method of pharmaceutical formulations in the form of orodispersible films according to the present invention may be siliconized polyester (PET) film conventionally used during the production of orodispersible films.
- PET siliconized polyester
- the drying process can be carried out at a temperature between 50°C - 150°C.
- the orodispersible film according to the present invention may have a thickness of 50 - 300 pm, preferably 50 - 150 pm, and a weight of 5 - 500 mg, more preferably 10 - 150 mg.
- the orodispersible film according to the present invention may have a size of 1 - 10 cm 2 , preferably the resulting orodispersible film has a size of 2.5 - 8 cm 2 . Additionally, the orodispersible films according to the present invention may be rectangular, square, circular, or an ellipse in shape, preferably resulting orodispersible films are rectangular in shape.
- the disintegration or dissolution of the orodispersible film according to the present invention once it is placed in the oral cavity depends on its contact with saliva, and the film disintegrates in less than 2 minutes, preferably less than 1 minute, and more preferably less than 45 seconds.
- the particle size of the active ingredient used in pharmaceutical formulations in the form of orodispersible film is a critical parameter in the production stage. Accordingly, eletriptan or pharmaceutically acceptable salt thereof used in the orodispersible film according to the present invention has a D90 particle size value which is below 60 pm.
- particle size refers to the volume diameter of particles, as measured by the laser diffraction method using a Malvern Mastersizer 2000.
- the D90 value represents the particle size by volume of 90% of the particles.
- the moisture content is 5 - 10%.
- Viscosity is another critical parameter to be considered in pharmaceutical formulations in the form of orodispersible film. Problems arise during the production of the film if the viscosity of the resulting mixture is too low or too high, preferably the viscosity of the orodispersible films according to the present invention is 7000 - 14000 cps.
- orodispersible film can appeal to a wide range of patient profiles. It is suitable for use by all patient groups, particularly those who have difficulty in swallowing, such as pediatric and geriatric patients. Moreover, orodispersible films are preferred dosage forms due to their rapid disintegration and effectiveness in the treatment of diseases such as migraine and headache, where taking rapid action is critical.
- compositions in the form of orodispersible film according to the present invention are characterized by comprising high amounts of eletriptan or pharmaceutically acceptable salt thereof.
- pharmaceutical formulations comprising high doses of eletriptan or a pharmaceutically acceptable salt thereof are obtained, which provide a rapid and efficient treatment onset and increase the bioavailability of eletriptan.
- compositions in the form of orodispersible film according to the present invention can be used in the treatment of cluster headaches, migraine, pain and chronic paroxysmal hemicrania, and vascular disorders associated with headache.
- Orodispersible film formulations comprising eletriptan hydrobromide were prepared according to the compounds shown in Table 1 below and their amounts in the unit formulation. Table. 1 - Compositions of orodispersible film formulations comprising eletriptan hydrobromide
- ethanol, polysorbate 80, polyethylene glycol 200 and glycerin are firstly placed into the production vessel and mixed.
- titanium dioxide, deionized water, and sucralose are slowly added, and the mixing is continued.
- Eletriptan hydrobromide is slowly added and mixed, and to this, FD&C Red solution, modified starch, pullulan and strawberry flavoring are added and the mixing is continued.
- the homogeneity of the mixture is checked.
- the resulting mixture is subjected to defoaming process, and until it is free of foam this process is continued.
- the resulting mixture is poured onto the siliconized PET film as a flat layer and subsequently subjected to drying with hot air.
- the films that reach the target thickness and weight are cut into the desired dimensions, and packaged.
- Example 2 and Example 3 exhibited very good results when the pharmaceutical formulations according to the present invention were prepared based on the unit formulas in Table.1 above. Accordingly, the comparative dissolution tests of Example 2 with the reference Relpax® tablet product are shown in Tables 2 - 4 below.
- the orodispersible films according to the present invention were prepared based on the unit formulas in Table.5 above, and the resulting films were compared in terms of their physical characteristics.
- Example 2 and Example 3 showed a similar dissolution profile with the reference tablet product in the state of the art, were able to disintegrate in less than 1 minute during a migraine attack, showed a rapid action, and became user- friendly with a pleasant taste when the data for the formulations prepared within the present invention are compared.
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Zoology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention porte sur des formulations de film orodispersible comprenant des quantités élevées d'élétriptan ou de sel pharmaceutiquement acceptable de celui-ci et l'utilisation de ces formulations dans le traitement de la migraine.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TR2020/13084A TR202013084A1 (tr) | 2020-08-19 | 2020-08-19 | Yüksek dozda eletriptan i̇çeren ağizda eri̇yen fi̇lm formülasyonlari |
PCT/TR2021/050624 WO2022039692A1 (fr) | 2020-08-19 | 2021-06-18 | Formulations de film orodispersible comprenant des doses élevées d'élétriptan |
Publications (1)
Publication Number | Publication Date |
---|---|
EP4199920A1 true EP4199920A1 (fr) | 2023-06-28 |
Family
ID=80350558
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP21858726.9A Pending EP4199920A1 (fr) | 2020-08-19 | 2021-06-18 | Formulations de film orodispersible comprenant des doses élevées d'élétriptan |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP4199920A1 (fr) |
TR (1) | TR202013084A1 (fr) |
WO (1) | WO2022039692A1 (fr) |
-
2020
- 2020-08-19 TR TR2020/13084A patent/TR202013084A1/tr unknown
-
2021
- 2021-06-18 EP EP21858726.9A patent/EP4199920A1/fr active Pending
- 2021-06-18 WO PCT/TR2021/050624 patent/WO2022039692A1/fr unknown
Also Published As
Publication number | Publication date |
---|---|
WO2022039692A1 (fr) | 2022-02-24 |
TR202013084A1 (tr) | 2022-03-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5717946B2 (ja) | ポリビニルアルコール−ポリエチレングリコールグラフト共重合体を含有する泡状ウェハ | |
JP4870386B2 (ja) | 口腔または体腔内で有効成分を放出するための迅速分解性投与可能剤形 | |
Nayak et al. | Current developments in orally disintegrating tablet technology | |
JP3460538B2 (ja) | 速溶性フィルム製剤 | |
CN104168895B (zh) | 包含西地那非作为活性成分的掩蔽苦味的高含量快速溶解膜 | |
AU2018281944B2 (en) | Quickly disintegrating foam wafer with high mass per unit area | |
WO2001089485A1 (fr) | Comprimes a desintegration rapide et procede de fabrication | |
US20120294940A1 (en) | Rapidly disintegrating tablet in oral cavity | |
JP2007517011A (ja) | 経口デリバリーのための多粒子製剤 | |
US20110086070A1 (en) | Orally disintegrating compositions of rhein or diacerein | |
JP2000500477A (ja) | 即時放出型の薬学的組成物 | |
WO2019202521A1 (fr) | Compositions de film à désintégration orale de paracétamol | |
EP4199920A1 (fr) | Formulations de film orodispersible comprenant des doses élevées d'élétriptan | |
JP2013501753A (ja) | 5−メチル−(6s)−テトラヒドロ葉酸塩を含む安定化粒子 | |
JP4196417B2 (ja) | 口腔内速崩錠及びその製造方法 | |
Pathak et al. | Recent Updates on Orally Disintegrating Thin Films | |
Sharma et al. | A review: formulation and characterization of fast dissolving tablet of carvidilol | |
CN116712415A (zh) | 一种多奈哌齐口溶膜及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE |
|
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 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE |
|
17P | Request for examination filed |
Effective date: 20230217 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
DAV | Request for validation of the european patent (deleted) | ||
DAX | Request for extension of the european patent (deleted) |