CN102596183A - 迅速溶出/崩解的包衣组合物 - Google Patents
迅速溶出/崩解的包衣组合物 Download PDFInfo
- Publication number
- CN102596183A CN102596183A CN2010800497688A CN201080049768A CN102596183A CN 102596183 A CN102596183 A CN 102596183A CN 2010800497688 A CN2010800497688 A CN 2010800497688A CN 201080049768 A CN201080049768 A CN 201080049768A CN 102596183 A CN102596183 A CN 102596183A
- Authority
- CN
- China
- Prior art keywords
- dosage form
- pharmaceutical dosage
- film coating
- film
- core
- 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.)
- Granted
Links
- 239000008199 coating composition Substances 0.000 title 1
- 239000007888 film coating Substances 0.000 claims abstract description 39
- 238000009501 film coating Methods 0.000 claims abstract description 39
- 239000007884 disintegrant Substances 0.000 claims abstract description 33
- 239000000463 material Substances 0.000 claims abstract description 22
- 239000002253 acid Substances 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims description 36
- 239000002552 dosage form Substances 0.000 claims description 33
- 239000003826 tablet Substances 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 26
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 11
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 11
- 238000004132 cross linking Methods 0.000 claims description 11
- 210000000214 mouth Anatomy 0.000 claims description 11
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 11
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 11
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 10
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000005516 engineering process Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 6
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 5
- 239000007910 chewable tablet Substances 0.000 claims description 5
- 229940068682 chewable tablet Drugs 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 229920002148 Gellan gum Polymers 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 3
- 239000002775 capsule Substances 0.000 claims description 3
- RRPFCKLVOUENJB-UHFFFAOYSA-L disodium;2-aminoacetic acid;carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O.NCC(O)=O RRPFCKLVOUENJB-UHFFFAOYSA-L 0.000 claims description 3
- 235000010492 gellan gum Nutrition 0.000 claims description 3
- 239000000216 gellan gum Substances 0.000 claims description 3
- 229920001282 polysaccharide Polymers 0.000 claims description 3
- 239000005017 polysaccharide Substances 0.000 claims description 3
- 150000004804 polysaccharides Chemical class 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 229920001285 xanthan gum Polymers 0.000 claims description 3
- 235000010493 xanthan gum Nutrition 0.000 claims description 3
- 239000000230 xanthan gum Substances 0.000 claims description 3
- 229940082509 xanthan gum Drugs 0.000 claims description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 2
- 235000010443 alginic acid Nutrition 0.000 claims description 2
- 229920000615 alginic acid Polymers 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 claims description 2
- 229960001126 alginic acid Drugs 0.000 claims description 2
- 150000004781 alginic acids Chemical class 0.000 claims description 2
- 235000012241 calcium silicate Nutrition 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 239000003456 ion exchange resin Substances 0.000 claims description 2
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 2
- 238000005253 cladding Methods 0.000 claims 1
- 238000005470 impregnation Methods 0.000 claims 1
- 229920000642 polymer Polymers 0.000 abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 6
- 238000000576 coating method Methods 0.000 description 43
- 239000011248 coating agent Substances 0.000 description 40
- 239000003795 chemical substances by application Substances 0.000 description 27
- 239000010408 film Substances 0.000 description 22
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 18
- 239000010409 thin film Substances 0.000 description 18
- 239000003814 drug Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 10
- 239000002245 particle Substances 0.000 description 9
- 229940069428 antacid Drugs 0.000 description 8
- 239000003159 antacid agent Substances 0.000 description 8
- 230000001458 anti-acid effect Effects 0.000 description 8
- 239000000796 flavoring agent Substances 0.000 description 8
- -1 hydroxypropyl Chemical group 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- 229960004756 ethanol Drugs 0.000 description 6
- 235000013355 food flavoring agent Nutrition 0.000 description 6
- 230000002496 gastric effect Effects 0.000 description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 230000000202 analgesic effect Effects 0.000 description 5
- 229910000019 calcium carbonate Inorganic materials 0.000 description 5
- 235000010216 calcium carbonate Nutrition 0.000 description 5
- 239000004014 plasticizer Substances 0.000 description 5
- 239000003495 polar organic solvent Substances 0.000 description 5
- KHOITXIGCFIULA-UHFFFAOYSA-N Alophen Chemical compound C1=CC(OC(=O)C)=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OC(C)=O)C=C1 KHOITXIGCFIULA-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 239000007894 caplet Substances 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 229960000935 dehydrated alcohol Drugs 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 238000005507 spraying Methods 0.000 description 4
- 239000007916 tablet composition Substances 0.000 description 4
- 229920003169 water-soluble polymer Polymers 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 229960001380 cimetidine Drugs 0.000 description 3
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 3
- 229960001596 famotidine Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 3
- 229960000991 ketoprofen Drugs 0.000 description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 3
- 239000001095 magnesium carbonate Substances 0.000 description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 3
- 239000000347 magnesium hydroxide Substances 0.000 description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229960002009 naproxen Drugs 0.000 description 3
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 230000000474 nursing effect Effects 0.000 description 3
- 229920006254 polymer film Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 3
- 229960000620 ranitidine Drugs 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 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 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 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 description 2
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 239000004376 Sucralose Substances 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 229960000503 bisacodyl Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007931 coated granule Substances 0.000 description 2
- 229920001688 coating polymer Polymers 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- HYPPXZBJBPSRLK-UHFFFAOYSA-N diphenoxylate Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 HYPPXZBJBPSRLK-UHFFFAOYSA-N 0.000 description 2
- 229960004192 diphenoxylate Drugs 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000007598 dipping method Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 229960000980 entecavir Drugs 0.000 description 2
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 description 2
- 239000003172 expectorant agent Substances 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 229960002390 flurbiprofen Drugs 0.000 description 2
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 2
- 229960001571 loperamide Drugs 0.000 description 2
- 239000000395 magnesium oxide Substances 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229960001929 meloxicam Drugs 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 229960000381 omeprazole Drugs 0.000 description 2
- 239000003605 opacifier Substances 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000004302 potassium sorbate Substances 0.000 description 2
- 235000010241 potassium sorbate Nutrition 0.000 description 2
- 229940069338 potassium sorbate Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- ZPMNHBXQOOVQJL-UHFFFAOYSA-N prucalopride Chemical compound C1CN(CCCOC)CCC1NC(=O)C1=CC(Cl)=C(N)C2=C1OCC2 ZPMNHBXQOOVQJL-UHFFFAOYSA-N 0.000 description 2
- 229960003863 prucalopride Drugs 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 235000013599 spices Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229960004291 sucralfate Drugs 0.000 description 2
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 2
- 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 description 2
- 235000019408 sucralose Nutrition 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 239000004408 titanium dioxide Substances 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
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- RJMIEHBSYVWVIN-LLVKDONJSA-N (2r)-2-[4-(3-oxo-1h-isoindol-2-yl)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1N1C(=O)C2=CC=CC=C2C1 RJMIEHBSYVWVIN-LLVKDONJSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- URLVCROWVOSNPT-XOTOMLERSA-N (2s)-4-[(13r)-13-hydroxy-13-[(2r,5r)-5-[(2r,5r)-5-[(1r)-1-hydroxyundecyl]oxolan-2-yl]oxolan-2-yl]tridecyl]-2-methyl-2h-furan-5-one Chemical compound O1[C@@H]([C@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@@H]([C@H](O)CCCCCCCCCCCCC=2C(O[C@@H](C)C=2)=O)CC1 URLVCROWVOSNPT-XOTOMLERSA-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
- MRAKLTZPBIBWFH-ARJAWSKDSA-N (z)-2-ethenylbut-2-enedioic acid Chemical compound OC(=O)\C=C(\C=C)C(O)=O MRAKLTZPBIBWFH-ARJAWSKDSA-N 0.000 description 1
- 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 description 1
- TYCOFFBAZNSQOJ-UHFFFAOYSA-N 2-[4-(3-fluorophenyl)phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC(F)=C1 TYCOFFBAZNSQOJ-UHFFFAOYSA-N 0.000 description 1
- XKSAJZSJKURQRX-UHFFFAOYSA-N 2-acetyloxy-5-(4-fluorophenyl)benzoic acid Chemical compound C1=C(C(O)=O)C(OC(=O)C)=CC=C1C1=CC=C(F)C=C1 XKSAJZSJKURQRX-UHFFFAOYSA-N 0.000 description 1
- OHXPGWPVLFPUSM-KLRNGDHRSA-N 3,7,12-trioxo-5beta-cholanic acid Chemical compound C1CC(=O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)C(=O)C[C@@H]3[C@]21C OHXPGWPVLFPUSM-KLRNGDHRSA-N 0.000 description 1
- SYCHUQUJURZQMO-UHFFFAOYSA-N 4-hydroxy-2-methyl-1,1-dioxo-n-(1,3-thiazol-2-yl)-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=CS1 SYCHUQUJURZQMO-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
- 241001116389 Aloe Species 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 239000010369 Cascara Substances 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 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
- 229920003149 Eudragit® E 100 Polymers 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- VPNYRYCIDCJBOM-UHFFFAOYSA-M Glycopyrronium bromide Chemical compound [Br-].C1[N+](C)(C)CCC1OC(=O)C(O)(C=1C=CC=CC=1)C1CCCC1 VPNYRYCIDCJBOM-UHFFFAOYSA-M 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 101000801619 Homo sapiens Long-chain-fatty-acid-CoA ligase ACSBG1 Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- 102100033564 Long-chain-fatty-acid-CoA ligase ACSBG1 Human genes 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- 240000007707 Mentha arvensis Species 0.000 description 1
- 235000018978 Mentha arvensis Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 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
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- XOYXESIZZFUVRD-UVSAJTFZSA-M acemannan Chemical compound CC(=O)O[C@@H]1[C@H](O)[C@@H](OC)O[C@H](CO)[C@H]1O[C@@H]1[C@@H](O)[C@@H](OC(C)=O)[C@H](O[C@@H]2[C@H]([C@@H](OC(C)=O)[C@H](O[C@@H]3[C@H]([C@@H](O)[C@H](O[C@@H]4[C@H]([C@@H](OC(C)=O)[C@H](O[C@@H]5[C@H]([C@@H](OC(C)=O)[C@H](O[C@@H]6[C@H]([C@@H](OC(C)=O)[C@H](O[C@@H]7[C@H]([C@@H](OC(C)=O)[C@H](OC)[C@@H](CO)O7)O)[C@@H](CO)O6)O)[C@H](O5)C([O-])=O)O)[C@@H](CO)O4)O)[C@@H](CO)O3)NC(C)=O)[C@@H](CO)O2)O)[C@@H](CO)O1 XOYXESIZZFUVRD-UVSAJTFZSA-M 0.000 description 1
- 229960005327 acemannan Drugs 0.000 description 1
- QUHYUSAHBDACNG-UHFFFAOYSA-N acerogenin 3 Natural products C1=CC(O)=CC=C1CCCCC(=O)CCC1=CC=C(O)C=C1 QUHYUSAHBDACNG-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
- SEIGJEJVIMIXIU-UHFFFAOYSA-J aluminum;sodium;carbonate;dihydroxide Chemical compound [Na+].O[Al+]O.[O-]C([O-])=O SEIGJEJVIMIXIU-UHFFFAOYSA-J 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 229950002342 bisfentidine Drugs 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 235000010634 bubble gum Nutrition 0.000 description 1
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 1
- 229960003184 carprofen Drugs 0.000 description 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 238000005266 casting Methods 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229960003609 cathine Drugs 0.000 description 1
- DLNKOYKMWOXYQA-IONNQARKSA-N cathine Chemical compound C[C@H](N)[C@@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-IONNQARKSA-N 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 229960003291 chlorphenamine Drugs 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- QBPFLULOKWLNNW-UHFFFAOYSA-N chrysazin Chemical compound O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O QBPFLULOKWLNNW-UHFFFAOYSA-N 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- 239000011362 coarse particle Substances 0.000 description 1
- 239000008373 coffee flavor Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- JURKNVYFZMSNLP-UHFFFAOYSA-N cyclobenzaprine Chemical compound C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 JURKNVYFZMSNLP-UHFFFAOYSA-N 0.000 description 1
- 229960003572 cyclobenzaprine Drugs 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 229960002997 dehydrocholic acid Drugs 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- URLVCROWVOSNPT-QTTMQESMSA-N desacetyluvaricin Natural products O=C1C(CCCCCCCCCCCC[C@@H](O)[C@H]2O[C@@H]([C@@H]3O[C@@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)=C[C@H](C)O1 URLVCROWVOSNPT-QTTMQESMSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960001271 desloratadine Drugs 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940015828 dihydroxyaluminum sodium carbonate Drugs 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical class OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 description 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
- 229960001395 fenbufen Drugs 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 229960003592 fexofenadine Drugs 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229950007979 flufenisal Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229950001284 fluprofen Drugs 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 229940015042 glycopyrrolate Drugs 0.000 description 1
- 229960002146 guaifenesin Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 1
- 229960004187 indoprofen Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229950002252 isoxicam Drugs 0.000 description 1
- YYUAYBYLJSNDCX-UHFFFAOYSA-N isoxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YYUAYBYLJSNDCX-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229960003174 lansoprazole Drugs 0.000 description 1
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 230000002475 laxative effect Effects 0.000 description 1
- 235000020094 liqueur Nutrition 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 1
- 229940061634 magnesium sulfate heptahydrate Drugs 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 201000003152 motion sickness Diseases 0.000 description 1
- 229940066491 mucolytics Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- FXJAOWANXXJWGJ-UHFFFAOYSA-N n-[4-(2-methyl-1h-imidazol-5-yl)phenyl]-n'-propan-2-ylmethanimidamide Chemical compound C1=CC(NC=NC(C)C)=CC=C1C1=CN=C(C)N1 FXJAOWANXXJWGJ-UHFFFAOYSA-N 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 description 1
- 229960004872 nizatidine Drugs 0.000 description 1
- 229960005343 ondansetron Drugs 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- NNGFFDRXGAELQA-UHFFFAOYSA-A pentaaluminum;decamagnesium;hentriacontahydroxide;disulfate Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O NNGFFDRXGAELQA-UHFFFAOYSA-A 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229960003733 phenylephrine hydrochloride Drugs 0.000 description 1
- OCYSGIYOVXAGKQ-FVGYRXGTSA-N phenylephrine hydrochloride Chemical compound [H+].[Cl-].CNC[C@H](O)C1=CC=CC(O)=C1 OCYSGIYOVXAGKQ-FVGYRXGTSA-N 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- PIDSZXPFGCURGN-UHFFFAOYSA-N pirprofen Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N1CC=CC1 PIDSZXPFGCURGN-UHFFFAOYSA-N 0.000 description 1
- 229960000851 pirprofen Drugs 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229960003101 pranoprofen Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
- 229960003908 pseudoephedrine Drugs 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000000407 respiratory system agent Substances 0.000 description 1
- 229940125704 respiratory tract agent Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 description 1
- 235000019982 sodium hexametaphosphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000005563 spheronization Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229950005175 sudoxicam Drugs 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000000152 swallowing effect Effects 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 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
- 229940072651 tylenol Drugs 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- 229940093612 zein Drugs 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种表现出增强的崩解特性的口服药物组合物,所述药物组合物包含芯以及所述芯上的薄膜包衣。所述薄膜包衣包含成膜聚合物、有机溶剂、超级崩解剂和任选的酸不稳定性材料。
Description
技术领域
本发明涉及药物组合物,更具体地讲,涉及具有增强的崩解特性的薄膜包衣片剂组合物。该薄膜包衣片剂组合物由含有以下物质的溶剂基薄膜包衣组合物包覆:可溶于水和极性有机溶剂的聚合物、超级崩解剂和任选的酸不稳定性材料。
背景技术
许多疾病治疗中的标准疗法是以片剂剂型施用药物活性成分,其通常需要患者完整地吞服片剂。为了改善片剂的可吞服性,本领域已知的是用聚合物薄膜包覆片剂表面,从而为患者提供若干益处。首先,其可降低片剂与口腔内表面的粘附力,从而增强患者吞服片剂的能力。其次,其可有助于掩盖某些药物的不良味道。另外,其还可保护组分免于在大气中降解并且可改善外观。
通常用于此类薄膜包衣的聚合物薄膜包含(例如):(1)乙烯基聚合物,如聚乙烯吡咯烷酮、聚乙烯醇和聚醋酸乙烯酯;(2)纤维素,如甲基纤维素和乙基纤维素、羟乙基纤维素、羟丙基甲基纤维素和羟丙基纤维素;(3)丙烯酸酯和甲基丙烯酸酯;(4)共聚物,如乙烯基-马来酸共聚物和苯乙烯-马来酸共聚物;以及(5)天然树胶和树脂,如玉米蛋白、明胶、紫胶和阿拉伯树胶。参见“Remington′s Pharmaceutical Sciences”,第15版,Mack Publishers(1975),第1613页。
虽然薄膜包衣可为片剂制剂增加某些优势,但有一个缺点是薄膜包衣可能会通过延迟片剂的崩解而减缓药物发挥作用。在某些情况下,这会延迟片剂在与液体介质接触的最初几分钟内的崩解。这会影响某些药物的性能,如需要快速发挥作用的抗酸剂。因此,需要表现出增强的崩解特性的薄膜包衣组合物,以便更快地递送活性物质以及更快地发挥作用。
在可吞服片制剂的片芯或制粒混合物中使用崩解剂(如干淀粉、藻酸钠、乳糖、碳酸氢钠、碳酸钙、聚乙烯吡咯烷酮、微晶纤维素等)是已知的。例如,美国专利No.4,965,072公开了使用七水硫酸镁和六偏磷酸钠的混合物与活性成分一起制备制粒组合物,当将其配制成可吞服片时,表现出快速崩解或分散特性。
近年来,已开发了多种更新的称为“超级崩解剂”的试剂。这些更新的物质在以较低浓度提供更高崩解效率和机械强度方面更有效。与水接触后,超级崩解剂即可溶胀、水合、改变体积或形成并产生片剂的破坏性变化。有效的超级崩解剂可提供改善的可压性、相容性,并且对含有高剂量药物的制剂的机械强度无负面影响。然而,以此类方式在片芯中使用崩解剂和/或超级崩解剂不能解决薄膜包衣片剂中与聚合物薄膜的溶出缓慢相关的问题。
授予R.P.Sheerer Corporation的美国专利No.6,413,549公开了快速崩解冻干剂型,其包含用聚合物或脂质材料包衣的活性物质的粗糙粒子。
授予SmithKline Beecham Corporation的美国专利No.7,125,562公开了崩解性甲基纤维素片。该专利公开说所述片剂具有第一相以及与第一相共混的第二相,并且每一相都可含有崩解剂和聚合物。
授予Hercules Incorporated的欧洲专利No.EP878189 B1公开了在个人护理产品中使用疏水改性的多糖,包括羟丙基纤维素。
授予Philip等人的美国专利申请No.20050255054公开了可溶性牙贴白,其包含可溶性物质,例如含乙酰化甘露聚糖的冻干水凝胶。
授予Wynn等人的美国专利申请No.20070077300 A1公开了这样的口服剂型,其包含可存在于剂型芯体中和/或包衣中的唾液诱生剂。
授予SmithKline Beecham Corporation的美国专利申请No.20080292669公开了适于透粘膜和/或透皮应用的发泡基质,其包含一种或多种聚合物以及一种或多种发泡剂,并且可包含一种或多种增塑剂、疏水性阻隔剂、牙齿增白剂、抗氧化剂、防腐剂、超级崩解剂或吸收剂、矫味剂、除臭剂、口气清新剂、着色剂、表面活性剂、薄膜改性剂、交联剂、抗微生物剂、控释剂、其他治疗剂或它们的任意组合。
授予Cambrex Charles City,Inc.的国际专利申请No.WO2008079963公开了含阴离子API(原料药)的离子络合物,其可用可药用包衣包覆。
授予Bangalore的美国专利申请No.20090047330 A1公开了基于水溶性聚合物的可食用薄膜,其使用该专利中所公开的制剂组合物及其他成分(包括增塑剂、填充剂、掩味剂、崩解剂和着色剂)而制备。
授予Bristol-Myers Squibb Co.的美国专利No.6,627,224公开了制备包含恩替卡韦的药物组合物的工艺,包括在溶剂中形成恩替卡韦和粘合剂的溶液,将该溶液沉积到基材粒子上,干燥包衣后的基质粒子并与其他成分(包括崩解剂)混合。
授予Ethypharm的美国专利No.6,660,382公开了制备能掩味并快速释放活性物质的包衣颗粒剂的工艺,包括:干混包含至少活性物质和崩解剂的粉末成分;在存在粘合剂的情况下对所得的粉末制粒以得到颗粒;通过喷洒包含至少一种包衣剂和一种崩解剂的悬浮液对颗粒进行包衣;以及干燥所得的包衣颗粒。
授予McNeil PPC,Inc.的美国专利No.5,807,580公开了包括表现出增强的崩解特性的薄膜包衣片的药物组合物,该片剂包含亲水性成膜聚合物和碱性剂(例如碱金属、碱土金属碳酸盐或碳酸氢盐,如碳酸氢钠或碳酸氢钾),其中碱性剂可通过提高薄膜包衣聚合物的移除速率而缩短薄膜包衣的崩解时间。
仍然需要药物组合物,更具体地讲,需要具有增强崩解特性的薄膜包衣片剂组合物。
发明内容
片剂上的速释薄膜包衣本身具有限速步骤,因为聚合物必须水合到一定程度后才能溶解,即便它们为水溶性薄膜包衣也是如此。大部分薄膜无法支持添加可有助于此崩解过程的材料,因为这些材料可能不与水性包衣溶液相容,或者就薄膜条剂型(film strip dosage form)而言,不与包含活性成分的浇注溶液相容。
本发明的药物组合物显示具有增强的崩解特性,其包含芯以及在芯上的薄膜包衣,该薄膜包衣包含成膜聚合物、极性有机溶剂、超级崩解剂和任选的酸不稳定性材料。选择既可溶于极性有机溶剂又可溶于水的聚合物,以便使超级崩解剂在施加(例如喷雾、浸渍或浇注成膜)前完整地悬浮。典型的水性包衣体系会在处理过程中使超级崩解剂失活,或者会溶胀到因尺寸过大而无法施加的程度。有机溶剂体系则允许它们在成品包衣中保持其溶胀特性。所述新型包衣组合物可产生快速溶出/崩解的薄膜。在整个包衣过程中超级崩解剂基本上完整。
超级崩解剂可通过薄膜的溶胀和崩解,增加薄膜包衣聚合物的移除速率来缩短薄膜包衣的崩解时间。酸不稳定性材料将会提高薄膜崩解速率。当该薄膜包衣片接触液体介质时,其立即与该液体介质反应以使薄膜包衣崩解。
优选地,成膜聚合物为羟丙基纤维素。
优选地,极性有机溶剂选自乙醇、丙酮、甲醇和异丙醇。在一个实施例中,极性有机溶剂为两种或更多种有机溶剂的混合物。在一个实施例中,该有机溶剂为乙醇与选自丙酮、甲醇和异丙醇的辅助溶剂的混合物,其中乙醇与辅助溶剂的比率为约50∶50至约99∶1。
优选地,超级崩解剂选自低取代羟丙基纤维素(L-HPC)、羧甲基淀粉钠、交联羧甲基纤维素钠、交联聚乙烯吡咯烷酮、大豆多糖、交联藻酸、结冷胶、黄原胶、硅酸钙和离子交换树脂。在一个优选的实施例中,超级崩解剂为交联羧甲基纤维素钠,因为其为离子型的。交联羧甲基纤维素钠的离子特性在制备和储存乙醇基包衣溶液或悬浮液时尤其有利,因为此特性可抑制溶液或悬浮液中超级崩解剂的反应或溶胀。在另一个优选的实施例中,超级崩解剂为L-HPC。
优选地,酸不稳定性材料选自碳酸氢钠、碳酸氢钾、碳酸钠和甘氨酸钠碳酸盐。
具体实施方式
根据本发明,在含有药物活性成分的芯的暴露表面的至少一部分上,优选整个表面上形成薄膜包衣。该薄膜包衣可任选含有:增塑剂,如蓖麻油、柠檬酸三乙酯、柠檬酸三丁酯、甘油三乙酸酯、矿物油、聚乙二醇、丙二醇或甘油;着色剂或遮光剂,如二氧化钛;调味剂;感觉剂,如凉爽剂、温热剂或麻刺剂;和/或改善适口性的甜味剂。薄膜包衣将通常含有约1重量%至约20重量%的成膜聚合物。
将薄膜包衣施加到含有活性成分的标准片剂或胶囊形片剂的芯上。芯根据标准药物制片技术制备,包括湿法制粒、干法制粒、直接压片、滚圆法等。使用常规的药物包衣设备将包衣材料施加到芯上,如使用得自Thomas Engineering,Inc.(Hoffman Estates,Ill)的Accela-CotaTM包衣锅或诸如Wurster包衣设备之类的流化床包衣装置。适用于本发明的其他薄膜包衣技术在“Remington′s Pharmaceutical Sciences”(A.L.Gennaro编辑),MackPublishing Co.(Easton,Pa.),第18版,第90章(1990)中有所描述,藉此将该文献以引用方式并入本文。施加本发明的薄膜包衣的优选方法是使用常规包衣设备进行喷雾包衣,但也可采用流化床包衣。
薄膜包衣(干燥的)通常占固体剂型总重量的约1至约10,优选约2至约6,更优选约2至约4重量%。在一个实施例中,干薄膜包衣的厚度为约30微米至约60微米。就咀嚼片剂而言,更优选地,薄膜包衣(干燥的)占固体剂型总重量的约0.2至约10重量%。同样就咀嚼片剂而言,更优选地,干薄膜包衣的厚度为约2微米至约40微米。
可采用本发明的薄膜包衣对多种需要快速发挥作用的活性物质进行包衣。与本发明的薄膜包衣一起使用的优选药物片剂含有抗酸剂,其中期望活性成分在胃中即刻释放以中和胃酸,并快速缓解酸过多性消化不良、胃灼热等。典型的抗酸剂由多种无机盐制成,如碳酸钙、碳酸氢钠、镁盐和铝盐。氢氧化镁和氢氧化铝是最有效的镁盐和铝盐,并且通常组合使用。此外,氧化镁、碳酸镁、磷酸铝、水化铝酸镁、三硅酸镁和蔗糖硫酸铝(硫糖铝)也可与本发明一起使用。在优选的实施例中,抗酸剂选自碳酸钙和碳酸镁或碳酸钙和氢氧化镁的组合。抗酸剂在制剂中的量可便利地在例如组合物的10%-90%w/v的范围内。有利的是,H2受体阻断剂如法莫替丁、雷尼替丁和/或西咪替丁也可与抗酸剂一起使用,或者可将薄膜包衣施加到H2受体阻断剂剂量中。本发明的包衣适用的其他活性成分包括抗胃肠气胀药、抗炎剂、止痛药、止泻药以及它们的组合。
如本文所用,术语“剂型”适用于设计为含有具体预定量(剂量)的某些成分(例如下文定义的活性成分)的任何固体物体、半固体或液体填充组合物。合适的剂型可以是给药体系,包括经口施用、颊面施用、直肠施用、局部或粘膜施用体系;皮下植入物或其他植入型药物递送体系;或递送矿物质、维生素和其他营养剂、口腔护理剂、香料等的组合物。优选地,将本发明的剂型考虑为固体,然而其可以含有液体组分或半固体组分。在特别优选的实施例中,剂型为用于将药物活性成分递送至人体胃肠道的经口施用体系。
适用于本发明的“活性成分”包括(例如)药物、矿物质、维生素和其他营养剂、口腔护理剂、香料以及它们的混合物。合适的药物包括:止痛药、抗炎剂、抗关节炎药、麻醉剂、抗组胺药、镇咳药、抗生素、抗感染剂、抗病毒剂、抗凝血剂、抗抑郁药、抗糖尿病剂、止吐药、抗胃肠气胀药、抗真菌剂、解痉药、食欲抑制剂、支气管扩张剂、心血管制剂、中枢神经系统制剂、中枢神经系统兴奋剂、减充血剂、口服避孕药、利尿剂、祛痰剂、胃肠制剂、偏头痛制剂、运动病产品、粘液溶解剂、肌肉松弛剂、骨质疏松症制剂、聚二甲基硅氧烷、呼吸制剂、助睡剂、尿道制剂以及它们的混合物。
合适的口腔护理剂包括口气清新剂、牙齿美白剂、抗微生物剂、牙齿矿化剂、牙齿防蛀剂、局部麻醉剂、粘膜保护剂等。
合适的矫味剂包括:薄荷醇、胡椒薄荷、薄荷风味剂、水果风味剂、巧克力、香草、泡泡糖风味剂、咖啡风味剂、利口酒风味剂以及它们的组合等。
合适的胃肠制剂的例子包括:诸如碳酸钙、氢氧化镁、氧化镁、碳酸镁、氢氧化铝、碳酸氢钠、二羟基铝碳酸钠之类的抗酸剂;诸如双醋苯啶、波希鼠李皮、二羟蒽醌、番泻叶、酚酞、芦荟、蓖麻油、蓖麻油酸、脱氢胆酸以及它们的混合物之类的刺激性缓泻剂;诸如法莫替丁、雷尼替丁、西咪替丁、尼扎替丁之类的H2受体拮抗剂;诸如奥美拉唑或兰索拉唑之类的质子泵抑制剂;诸如硫糖铝和米索前列醇之类的胃肠细胞保护剂;诸如普卢卡必利之类的胃肠促动药;针对幽门螺旋杆菌(H.pylori)的抗生素,如克拉霉素、阿莫西林、四环素和甲硝唑;诸如地芬诺酯和洛哌丁胺之类的止泻剂;甘罗溴铵;诸如昂丹司琼之类的止吐药;诸如美沙胺之类的止痛药。优选的胃肠制剂为奥美拉唑。
在本发明的一个实施例中,活性成分可选自双醋苯啶、法莫替丁、雷尼替丁、西咪替丁、普卢卡必利、地芬诺酯、洛哌丁胺、乳糖酶、美沙胺、铋、抗酸剂以及它们的可药用盐、酯、异构体和混合物。
在另一个实施例中,活性成分选自止痛药、抗炎剂和退热剂:例如非甾体抗炎药(NSAID),包括丙酸衍生物,例如布洛芬、萘普生、酮洛芬等;乙酸衍生物,例如消炎痛、双氯芬酸、舒林酸、托美丁等;灭酸衍生物,例如甲灭酸、甲氯芬那酸、氟芬那酸等;联苯基甲酸衍生物,例如二氟苯水杨酸、氟苯沙酸等;和昔康类,例如吡罗昔康、舒多昔康、伊索昔康、美洛昔康等。在一个具体实施例中,活性成分选自丙酸衍生物NSAID,例如布洛芬、萘普生、氟比洛芬、芬布芬、非诺洛芬、吲哚洛芬、酮洛芬、氟洛芬、吡洛芬、卡洛芬、噁丙嗪、普拉洛芬、舒洛芬以及它们的可药用盐、衍生物和组合。在本发明另一个具体实施例中,活性成分可选自:对乙酰氨基酚、乙酰水杨酸、布洛芬、萘普生、酮洛芬、氟比洛芬、双氯芬酸、环苯扎林、美洛昔康、罗非考昔、塞来考昔以及它们的可药用盐、酯、异构体和混合物。优选的(止痛药)为对乙酰氨基酚。
在本发明的另一个实施例中,活性成分可选自上呼吸道剂,如伪麻黄碱、去氧肾上腺素、愈创木酚甘油醚、去甲麻黄碱、扑尔敏、右美沙芬、苯海拉明、阿司咪唑、特非那定、非索非那定、氯雷他定、地氯雷他定、西替利嗪及其混合物,以及它们的可药用盐、酯、异构体和混合物。
所述一种或多种活性成分以治疗有效量存在于剂型中,治疗有效量为口服时产生所需治疗响应的量并易于由本领域的技术人员确定。在确定这种量时,必须考虑要给药的具体活性成分、活性成分的生物利用率特性、给药方案、患者的年龄和体重以及其他因素,如本领域所知的。通常,剂型包含至少约1重量%,例如剂型包含至少约5重量%(比方说至少约20重量%)的一种或多种活性成分的组合。在一个实施例中,芯总共包含至少约25重量%(以芯的重量计)的一种或多种活性成分。
活性成分可以按任何形式存在于剂型中。
每个芯可以是任何固体形式。如本文所用,“芯”指至少部分地被另一种材料包封或围绕并具有至少约2mm至约30mm厚度的材料。优选地,芯是整装的一体式物体,如片剂或胶囊。通常,芯包含固体,例如,芯可以是压制片或模制片或者为硬胶囊或软胶囊。
在一个实施例中,芯为能够咀嚼(即,咀嚼片剂)或能够在口腔中崩解的片剂。在一个实施例中,将片剂设计为当放置在舌头上时在短于约60秒(例如短于约45秒,例如短于约30秒,例如短于约15秒)内在口内崩解。本发明的薄膜包衣在用作咀嚼片剂或口腔崩解片剂的包衣时将尤其有利,因为它能足够快地崩解,从而允许片芯被嚼碎或类似地发生崩解。其他类型的包衣缓慢崩解,使得可能非有意地吞下剂型,或在口内留下不适口的薄膜或薄膜碎片。
在一个实施例中,片剂符合2007年4月出版的食品药品监督管理局指南草案(draft Food and Drug Administration guidance)所定义的口腔崩解片剂(ODT)的标准。在一个实施例中,片剂符合包括下述标准的适用于口腔崩解片剂的双重定义:1)该固体片剂为含有药用物质并且在置于舌头上时快速地,通常在几秒内崩解的片剂,和2)被视为在口腔中快速崩解的固体口服制剂,其在根据美国药典(USP)用于一种或多种特定药用物质的崩解测试方法测试时,体外崩解时间为大约30秒或更短。
芯可通过任何合适的方法制备,包括(例如)压制和模制,并取决于其制备方法,通常包含活性成分和多种赋形剂。
在本发明的一个实施例中,将剂型用作底衣,并且进一步用凝胶包衣材料进行包衣或部分包衣。在一个实施例中,底衣包括暴露出芯的开口,并且进一步增强剂型的崩解。凝胶包衣可通过多种方法(包括浸渍、模制或包覆)施加,并可包含诸如明胶、结冷胶、淀粉、羟丙甲纤维素或改性淀粉之类的包衣材料以及诸如角叉菜胶和黄原胶之类的增稠剂。在一个实施例中,使用激光在底衣中产生开口。
在一个实施例中,包衣溶液或悬浮液基本上不含水。如本文所用,“基本上不含”定义为低于0.5%(如低于0.2%)的水。在一个实施例中,薄膜条溶液或悬浮液基本上不含水。如本文所用,“基本上不含”定义为低于0.5%(如低于0.2%)的水。
当将活性成分掺入薄膜中作为剂型时,其可以任何形式存在于剂型中。例如,可以分子水平(例如熔融或溶解)将活性成分分散在剂型内,或者活性成分可为粒子形式,继而又可对粒子进行包衣或不包衣。如果活性成分为粒子形式,则粒子(无论包衣还是未包衣)的平均粒度通常为约1微米至约2000微米。在一个实施例中,此类粒子为平均粒度为约1微米至约300微米的晶体。在另一个实施例中,粒子为平均粒度为约50微米至约2000微米,例如约50微米至约1000微米或约100微米至约800微米的颗粒或小丸。在另一个实施例中,本发明的包衣包含着色剂,其可以包括色淀、染料或遮光剂(如二氧化钛)或它们的混合物。
通过以下实例来举例说明本发明的具体实施例。本发明不受这些实例中提出的具体限制因素的限制,而是受限于所附权利要求的范围。除非另外指明,否则本文所公开的百分比和比率均按重量计。
实例
将聚合物(例如聚乙烯醇、聚乙烯吡咯烷酮、乙烯基吡咯烷酮与乙酸乙烯酯的共聚物、羟丙基纤维素和Eudragit E100)溶于有机溶剂(例如醇、酮、酯和卤化烃)中。然后,将超级崩解剂(例如低取代羟丙基纤维素(L-HPC)、羧甲淀粉钠、交联羧甲基纤维素钠)分散在所得的聚合物溶液中。在采用时,也将酸不稳定性材料(例如碳酸钠、碳酸氢钠、甘氨酸钠碳酸盐)分散在所得的聚合物溶液中。
可通过喷雾法或浸渍法将包衣组合物施加到片剂、胶囊剂或胶囊形片剂上。该包衣体系干燥成聚合物膜,并且提供在基材上形成截然不同的快速溶出/崩解的外壳所需的本体。
组合物:
A.在无水乙醇中包含约5-15%固形物的成膜组合物,具有:
-水溶性聚合物,如HPC(约2-8%的总溶液)
-超级崩解剂,如L-HPC(约3-10%的总溶液)
-任选的酸不稳定性材料,如碳酸氢钠(约0-5%的总溶液)
-任选的增塑剂,如PEG 400(约0-4%的总溶液)
B.具有快速崩解包衣的剂型,包含:
-水溶性聚合物(约15-40%)
-超级崩解剂,如交联羧甲基纤维素钠(约50-75%)
-任选的酸不稳定性材料,如碳酸钠(约0-30%)
-任选的增塑剂,如PEG-400(约0-25%)
(有利的是,包衣在暴露于胃肠液时立即崩解,从而避免活性成分溶出时间拖延)。
工艺选项:
包衣组合物适用于喷雾和浸渍施加。
实例
实例1:快速溶出HPC薄膜包衣
包含HPC和超级崩解剂的包衣溶液的制备
1)在室温下通过顶置式搅拌器将5.75g羟丙基纤维素(HPC,以商品名Klucel EF从Ashland Corporation(Covington,KY)商购获得)混合到207g无水乙醇中,得到2.7%固形物的HPC溶液。
2)然后在室温伴随搅拌下将17.25g交联羧甲基纤维素钠(以商品名Ac-Di-Sol从FMC Corporation(Philadelphia,PA)商购获得的超级崩解剂)添加到HPC溶液中,得到10%固形物的HPC/交联羧甲基纤维素钠悬浮液。
片芯的薄膜包衣
将市售的Tylenol超强度不带涂层的胶囊形片剂(900g)装到12英寸的通风包衣锅(可从O’Hara Technologies(Richmond Hill,ON,Canada)商购获得)中。按以下条件对该批胶囊形片剂进行喷雾包衣:大约10克/分钟的喷雾速率,约10RPM的包衣锅转速,约56℃的进气温度,约25psi的雾化气压。喷涂115g包衣悬浮液,其相当于23g干包衣或约2.5%增重。
将包衣片放入盛有900mL纯化水的容器中,其中包衣在短于15秒内崩解。许多市售包衣片上的包衣需要数分钟才能崩解。
实例2:基于快速溶解HPC薄膜的剂型
包含HPC和超级崩解剂的薄膜浇注溶液的制备
根据表1制备基于口腔溶解薄膜的剂型。
1)在室温下通过顶置式实验室搅拌器以20RPM的转速搅拌20分钟,将13.78g HPC混合到261.8g无水乙醇中,得到5%固形物的HPC溶液。
2)将三氯蔗糖、山梨酸钾、覆盆子风味剂和盐酸去氧肾上腺素添加至上述混合物。
3)然后在室温下以20RPM的转速搅拌将交联羧甲基纤维素钠和剩余的乙醇加到该HPC溶液中,得到15%固形物的悬浮液。
表1:口腔溶解薄膜配方
材料 | Mg/溶液 | mg/干薄膜 | %/干薄膜 |
羟丙基纤维素 | 13.78 | 13.78 | 21.200 |
交联羧甲基纤维素钠 | 41.33 | 41.33 | 63.585 |
去氧肾上腺素 | 7.50 | 7.50 | 11.539 |
三氯蔗糖 | 1.50 | 1.50 | 2.308 |
覆盆子风味剂 | 0.80 | 0.80 | 1.231 |
山梨酸钾 | 0.09 | 0.09 | 0.139 |
乙醇 | 152.0 | NA* | NA* |
总计 | 217.0 | 65.00 | 100.00 |
*干燥移除
薄膜条制备
1)将大约217.0mg悬浮液倒入具有边缘的玻璃板上。
2)然后在室温下将该混合物干燥5-6小时,直到表面干燥。
3)将样品从玻璃板上取下。
实例3:无崩解剂的羟丙基纤维素薄膜比较例
1)在室温下通过顶置式搅拌器将6.00g羟丙基纤维素(HPC,以商品名Klucel EF从Ashland Corporation(Covington,KY)商购获得)混合到94g无水乙醇中,得到6%固形物的HPC溶液。
2)将(1)中的大约2g溶液浇注成大约1mm的薄膜,在40℃下干燥1小时。
3)将实例1中制得的大约2g溶液(包含超级崩解剂)浇注成大约6.5mm、5mm和3.5mm的薄膜,让其在40℃下干燥1小时。
4)将包含超级崩解剂和无超级崩解剂的薄膜安装到溶出仪上,并置于400ml烧杯的中央。将250mL 25℃的纯化水倒入烧杯中以接触薄膜表面。相应地记录崩解时间。对于6.5密耳、5密耳和3.5密耳的膜,包含超级崩解剂的HPC薄膜(根据实例1制备)分别在11秒、6秒和3秒内崩解。不使用超级崩解剂制备的HPC薄膜(1密耳)的崩解时间超过4分钟。这一结果出人意料,因为无超级崩解剂的薄膜比具有超级崩解剂的对应薄膜更薄,而更薄的膜通常会以更快的速率崩解。
尽管上面仅具体描述了本发明优选的实施例,但应该理解,本发明的修改形式和变化形式是可能的,只要不脱离本发明的精神和预期范围。
Claims (17)
1.一种包含芯和薄膜包衣的药物剂型,其中所述薄膜包衣包含羟丙基纤维素和超级崩解剂。
2.根据权利要求1所述的药物剂型,其中所述芯的厚度为至少约2mm至约30mm。
3.根据权利要求1所述的药物剂型,其中所述薄膜包衣在水中的崩解时间短于10秒。
4.根据权利要求1所述的药物剂型,其中所述超级崩解剂选自交联羧甲基纤维素钠、交联聚乙烯吡咯烷酮、羧甲基淀粉钠、低取代羟丙基纤维素(L-HPC)、多糖、交联藻酸、结冷胶、黄原胶、硅酸钙和离子交换树脂。
5.根据权利要求4所述的药物剂型,其中所述超级崩解剂选自交联羧甲基纤维素钠和低取代羟丙基纤维素(L-HPC)。
6.根据权利要求1所述的药物剂型,其中所述薄膜包衣还包含酸不稳定性材料。
7.根据权利要求6所述的药物剂型,其中所述酸不稳定性材料选自碳酸氢钠、碳酸氢钾、碳酸钠和甘氨酸钠碳酸盐。
8.根据权利要求1所述的药物剂型,还包括从所述薄膜包衣的表面延伸到所述芯的表面的开口。
9.根据权利要求1所述的药物剂型,其中所述芯选自片剂和胶囊剂。
10.根据权利要求9所述的药物剂型,其中所述片剂选自咀嚼片剂和口腔崩解片剂。
11.一种制备药物剂型的方法,包括制备薄膜包衣;以及将所述薄膜包衣施加到芯上,其中制备所述薄膜包衣包括将超级崩解剂悬浮在有机溶剂中的步骤以及将羟丙基纤维素溶解于所述有机溶剂中的步骤。
12.根据权利要求11所述的方法,其中所述有机溶剂选自乙醇、丙酮、甲醇和异丙醇。
13.根据权利要求11所述的方法,其中所述有机溶剂为两种或更多种有机溶剂的混合物。
14.根据权利要求13所述的方法,其中所述有机溶剂为乙醇与选自丙酮、甲醇和异丙醇的辅助溶剂的混合物。
15.根据权利要求14所述的方法,其中乙醇与辅助溶剂的比率为约50∶50至约99∶1。
16.根据权利要求11所述的方法,其中通过选自喷雾工艺、浸渍工艺以及浇注和包覆工艺的工艺将所述薄膜包衣施加到所述芯上。
17.根据权利要求11所述的方法,其中所述薄膜包衣包含活性成分。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US25562609P | 2009-10-28 | 2009-10-28 | |
US61/255,626 | 2009-10-28 | ||
PCT/US2010/054431 WO2011056702A2 (en) | 2009-10-28 | 2010-10-28 | Fast dissolving/disintegrating coating compositions |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102596183A true CN102596183A (zh) | 2012-07-18 |
CN102596183B CN102596183B (zh) | 2014-09-17 |
Family
ID=43898638
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201080049768.8A Expired - Fee Related CN102596183B (zh) | 2009-10-28 | 2010-10-28 | 迅速溶出/崩解的包衣组合物 |
Country Status (7)
Country | Link |
---|---|
US (1) | US8367104B2 (zh) |
EP (1) | EP2493454A2 (zh) |
CN (1) | CN102596183B (zh) |
AU (1) | AU2010315414B2 (zh) |
BR (1) | BR112012010170A2 (zh) |
CA (1) | CA2778273A1 (zh) |
WO (1) | WO2011056702A2 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103006602A (zh) * | 2013-01-04 | 2013-04-03 | 青岛大学 | 一种快速溶出的阿托伐他汀钙片及其制备方法 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8529914B2 (en) * | 2010-06-28 | 2013-09-10 | Richard C. Fuisz | Bioactive dose having containing a material for modulating pH of a bodily fluid to help or hinder absorption of a bioactive |
CN102885798B (zh) * | 2011-07-21 | 2015-04-22 | 成都康弘药业集团股份有限公司 | 一种口腔崩解片 |
US20140315930A1 (en) * | 2011-11-14 | 2014-10-23 | Hetero Research Foundation | Fast release solid oral compositions of entecavir |
CA2880163A1 (en) * | 2012-08-01 | 2014-02-06 | Acura Pharmaceuticals, Inc. | Stabilization of one-pot methamphetamine synthesis systems |
CA3029985A1 (en) | 2016-07-05 | 2018-01-11 | Glaxosmithkline Consumer Healthcare Holdings (Us) Llc | Oral dosage form containing a fast release exterior coating |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1308520A (zh) * | 1998-03-20 | 2001-08-15 | 安得克斯制药公司 | 具有单一核心的控释口服片剂 |
US20060003007A1 (en) * | 2004-07-01 | 2006-01-05 | Isa Odidi | Controlled extended drug release technology |
US20060188570A1 (en) * | 1998-05-27 | 2006-08-24 | Udit Batra | Compressed tablet formulation |
WO2007103286A2 (en) * | 2006-03-02 | 2007-09-13 | Spherics, Inc. | Rate-controlled bioadhesive oral dosage formulations |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4965072A (en) | 1988-11-03 | 1990-10-23 | Miles Inc. | Granulating composition and method |
ATE197900T1 (de) * | 1996-08-15 | 2000-12-15 | Losan Pharma Gmbh | Gut schluckbare orale arzneiform |
US5807580A (en) | 1996-10-30 | 1998-09-15 | Mcneil-Ppc, Inc. | Film coated tablet compositions having enhanced disintegration characteristics |
US6905694B1 (en) | 1997-05-12 | 2005-06-14 | Hercules Incorporated | Hydrophobically modified polysaccharide in personal care products |
US5976577A (en) * | 1997-07-11 | 1999-11-02 | Rp Scherer Corporation | Process for preparing fast dispersing solid oral dosage form |
AR017512A1 (es) * | 1997-08-22 | 2001-09-12 | Smithkline Beecham Corp | Tabletas de metilcelulosa rapidamente desintegrables para administracion por via oral y procedimiento para prepararlas |
US6099865A (en) * | 1998-07-08 | 2000-08-08 | Fmc Corporation | Croscarmellose taste masking |
FR2795962B1 (fr) | 1999-07-08 | 2003-05-09 | Prographarm Laboratoires | Procede de fabrication de granules enrobes a gout masque et liberation immediate du principe actif |
RS51561B (sr) * | 2000-02-29 | 2011-08-31 | Bristol-Myers Squibb Co. | Formulacija male doze entekavira i upotreba |
RU2375048C2 (ru) * | 2003-07-17 | 2009-12-10 | Д-Р Редди'С Лабораторис Инк. | Фармацевтическая композиция с набухающим покрытием |
US20050255054A1 (en) * | 2004-04-30 | 2005-11-17 | Philp Graham K Jr | Method for tooth whitening, in particular a system for tooth whitening using a dissolvable tray or strip |
US20070077300A1 (en) * | 2005-09-30 | 2007-04-05 | Wynn David W | Oral compositions containing a salivation inducing agent |
CA2629612A1 (en) * | 2005-11-22 | 2007-05-31 | Smithkline Beecham Corporation | Foamed substrate and method for making same |
WO2008079963A2 (en) | 2006-12-22 | 2008-07-03 | Cambrex Charles City, Inc. | Pharmaceutical compositions comprising ionic complexes of active pharmaceutical ingredients |
US20090047330A1 (en) | 2007-08-17 | 2009-02-19 | Ramesh Bangalore | Oral fast dissolving films for erectile dysfunction bioactive agents |
-
2010
- 2010-10-28 BR BR112012010170A patent/BR112012010170A2/pt not_active IP Right Cessation
- 2010-10-28 CN CN201080049768.8A patent/CN102596183B/zh not_active Expired - Fee Related
- 2010-10-28 AU AU2010315414A patent/AU2010315414B2/en not_active Ceased
- 2010-10-28 WO PCT/US2010/054431 patent/WO2011056702A2/en active Application Filing
- 2010-10-28 US US12/913,855 patent/US8367104B2/en not_active Expired - Fee Related
- 2010-10-28 EP EP10774389A patent/EP2493454A2/en not_active Withdrawn
- 2010-10-28 CA CA2778273A patent/CA2778273A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1308520A (zh) * | 1998-03-20 | 2001-08-15 | 安得克斯制药公司 | 具有单一核心的控释口服片剂 |
US20060188570A1 (en) * | 1998-05-27 | 2006-08-24 | Udit Batra | Compressed tablet formulation |
US20060003007A1 (en) * | 2004-07-01 | 2006-01-05 | Isa Odidi | Controlled extended drug release technology |
WO2007103286A2 (en) * | 2006-03-02 | 2007-09-13 | Spherics, Inc. | Rate-controlled bioadhesive oral dosage formulations |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103006602A (zh) * | 2013-01-04 | 2013-04-03 | 青岛大学 | 一种快速溶出的阿托伐他汀钙片及其制备方法 |
CN103006602B (zh) * | 2013-01-04 | 2015-06-10 | 青岛大学 | 一种快速溶出的阿托伐他汀钙片及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
WO2011056702A3 (en) | 2011-11-17 |
AU2010315414B2 (en) | 2015-07-09 |
WO2011056702A2 (en) | 2011-05-12 |
AU2010315414A1 (en) | 2012-05-17 |
EP2493454A2 (en) | 2012-09-05 |
US20110097399A1 (en) | 2011-04-28 |
CN102596183B (zh) | 2014-09-17 |
BR112012010170A2 (pt) | 2016-04-12 |
CA2778273A1 (en) | 2011-05-12 |
US8367104B2 (en) | 2013-02-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8927014B2 (en) | Misuse preventative, controlled release formulation | |
US9572803B2 (en) | Abuse resistant drug formulation | |
DK2200593T5 (en) | Hog-resistant pharmaceutical formulation | |
JP5604304B2 (ja) | 口腔内崩壊性固形製剤 | |
CN102596183B (zh) | 迅速溶出/崩解的包衣组合物 | |
JP2009292843A (ja) | 固形製剤 | |
CN101686934A (zh) | 双部分糖锭剂型 | |
CN101677967A (zh) | 调释固体或半固体剂型 | |
JP2010132709A (ja) | 速崩壊性固形製剤 | |
CN101472568A (zh) | 含有活性成分的肠衣颗粒 | |
BR112015021403B1 (pt) | Composição oral sólida antitussígena de liberação modificada compreendendo enzonatato em uma matriz | |
NZ516341A (en) | Texture masked particles comprising an active ingredient coated with a film forming polymer and an anti-grit agent | |
CN106456550A (zh) | 避免乙醇剂量倾泻的多颗粒 | |
JP2011512411A (ja) | 高アミロース含量を有するデンプンを含有する浸漬コーティングされた組成物 | |
CN102470111A (zh) | 含充液胶囊的药物片剂 | |
KR20130010463A (ko) | 고형 제제 | |
CA2956947C (en) | Core compositions | |
WO2006049683A1 (en) | Immediate release film coating | |
JP4939680B2 (ja) | 固形製剤 | |
CN109646412B (zh) | 一种肠溶药用组合物及其制备方法和应用 | |
JP5614445B2 (ja) | 経口投与用粒子状医薬組成物 | |
CN102727456B (zh) | 药物口腔崩解片及其制备方法 | |
KR101680925B1 (ko) | 불쾌미 마스킹 입자 및 이것을 함유하는 경구제제 | |
CN102639122A (zh) | 调释剂型的部分浸渍包衣 | |
BR112020014457A2 (pt) | cápsulas perfuradas |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140917 Termination date: 20171028 |