CA2515025A1

CA2515025A1 - Sugar-free oral transmucosal solid dosage forms and uses thereof

Sugar-free oral transmucosal solid dosage forms and uses thereof Download PDF

Info

Publication number: CA2515025A1
Authority: CA; Canada
Prior art keywords: composition according; dosage form; sugar; solid dosage; polyhydric alcohol
Prior art date: 2003-02-04
Legal status : Abandoned

Application number

CA002515025A

Other languages

English (en)

French (fr)

Inventor

Brian Hague

Lynn J. Maland

Current Assignee

Cephalon LLC

Original Assignee

Individual

Priority date

2003-02-04

Filing date

2004-02-04

Publication date

2004-08-19

2004-02-04 Application filed by Individual filed Critical Individual

2004-08-19 Publication of CA2515025A1 publication Critical patent/CA2515025A1/en

Status Abandoned legal-status Critical Current

Links

239000007909 solid dosage form Substances 0.000 title claims abstract description 133
239000000203 mixture Substances 0.000 claims abstract description 226
239000008177 pharmaceutical agent Substances 0.000 claims abstract description 66
239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 60
235000000346 sugar Nutrition 0.000 claims abstract description 59
238000004090 dissolution Methods 0.000 claims abstract description 34
210000003296 saliva Anatomy 0.000 claims abstract description 26
IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 claims description 116
150000005846 sugar alcohols Polymers 0.000 claims description 58
239000000905 isomalt Substances 0.000 claims description 54
235000010439 isomalt Nutrition 0.000 claims description 54
HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 claims description 54
229960002428 fentanyl Drugs 0.000 claims description 52
239000000872 buffer Substances 0.000 claims description 51
238000000034 method Methods 0.000 claims description 51
229960004207 fentanyl citrate Drugs 0.000 claims description 47
239000002552 dosage form Substances 0.000 claims description 44
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 40
229920001223 polyethylene glycol Polymers 0.000 claims description 32
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 30
239000000600 sorbitol Substances 0.000 claims description 30
235000010356 sorbitol Nutrition 0.000 claims description 30
SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 claims description 29
239000007787 solid Substances 0.000 claims description 29
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 28
239000002253 acid Substances 0.000 claims description 28
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 26
229930195725 Mannitol Natural products 0.000 claims description 26
239000000594 mannitol Substances 0.000 claims description 26
235000010355 mannitol Nutrition 0.000 claims description 26
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 25
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 25
239000000811 xylitol Substances 0.000 claims description 25
235000010447 xylitol Nutrition 0.000 claims description 25
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 25
229960002675 xylitol Drugs 0.000 claims description 25
239000000843 powder Substances 0.000 claims description 23
239000002202 Polyethylene glycol Substances 0.000 claims description 22
210000000214 mouth Anatomy 0.000 claims description 21
DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 20
229960002920 sorbitol Drugs 0.000 claims description 20
239000008194 pharmaceutical composition Substances 0.000 claims description 19
208000002193 Pain Diseases 0.000 claims description 18
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 18
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 18
238000010521 absorption reaction Methods 0.000 claims description 18
239000011230 binding agent Substances 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
230000036407 pain Effects 0.000 claims description 15
239000000832 lactitol Substances 0.000 claims description 13
235000010448 lactitol Nutrition 0.000 claims description 13
VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol 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-JVCRWLNRSA-N 0.000 claims description 13
229960003451 lactitol Drugs 0.000 claims description 13
239000000845 maltitol Substances 0.000 claims description 12
235000010449 maltitol Nutrition 0.000 claims description 12
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 12
229940035436 maltitol Drugs 0.000 claims description 12
230000001013 cariogenic effect Effects 0.000 claims description 11
235000009508 confectionery Nutrition 0.000 claims description 11
239000012458 free base Substances 0.000 claims description 11
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 10
229920001100 Polydextrose Polymers 0.000 claims description 10
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 10
239000000314 lubricant Substances 0.000 claims description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
229960001855 mannitol Drugs 0.000 claims description 10
210000004400 mucous membrane Anatomy 0.000 claims description 10
239000001259 polydextrose Substances 0.000 claims description 10
235000013856 polydextrose Nutrition 0.000 claims description 10
229940035035 polydextrose Drugs 0.000 claims description 10
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 9
239000004386 Erythritol Substances 0.000 claims description 8
UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 8
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 8
235000019414 erythritol Nutrition 0.000 claims description 8
229940009714 erythritol Drugs 0.000 claims description 8
UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 8
239000008103 glucose Substances 0.000 claims description 8
210000002200 mouth mucosa Anatomy 0.000 claims description 8
229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 7
229940061607 dibasic sodium phosphate Drugs 0.000 claims description 7
235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 7
239000005017 polysaccharide Substances 0.000 claims description 7
150000004804 polysaccharides Polymers 0.000 claims description 7
229930006000 Sucrose Natural products 0.000 claims description 6
239000011734 sodium Substances 0.000 claims description 6
229910052708 sodium Inorganic materials 0.000 claims description 6
239000005720 sucrose Substances 0.000 claims description 6
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 5
239000007983 Tris buffer Substances 0.000 claims description 5
239000001863 hydroxypropyl cellulose Substances 0.000 claims description 5
235000019359 magnesium stearate Nutrition 0.000 claims description 5
150000002482 oligosaccharides Polymers 0.000 claims description 5
BUCIWTBCUUHRHZ-UHFFFAOYSA-K potassium;disodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[K+].OP(O)([O-])=O.OP([O-])([O-])=O BUCIWTBCUUHRHZ-UHFFFAOYSA-K 0.000 claims description 5
LJSOLTRJEQZSHV-UHFFFAOYSA-L potassium;sodium;hydron;hydroxide;phosphate Chemical compound [OH-].[Na+].[K+].OP(O)([O-])=O LJSOLTRJEQZSHV-UHFFFAOYSA-L 0.000 claims description 5
RHZZMUCBMSWAHK-UAIGNFCESA-M sodium;(z)-but-2-enedioic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)\C=C/C(O)=O RHZZMUCBMSWAHK-UAIGNFCESA-M 0.000 claims description 5
LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 claims description 5
208000000003 Breakthrough pain Diseases 0.000 claims description 4
CBMPTFJVXNIWHP-UHFFFAOYSA-L disodium;hydrogen phosphate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].OP([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CBMPTFJVXNIWHP-UHFFFAOYSA-L 0.000 claims description 4
150000004676 glycans Polymers 0.000 claims description 4
159000000001 potassium salts Chemical class 0.000 claims description 4
208000000094 Chronic Pain Diseases 0.000 claims description 3
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 3
206010027599 migraine Diseases 0.000 claims description 3
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 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
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 2
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 2
229930091371 Fructose Natural products 0.000 claims description 2
239000005715 Fructose Substances 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
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 2
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 2
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 2
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 2
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 2
229930182830 galactose Natural products 0.000 claims description 2
239000008101 lactose Substances 0.000 claims description 2
IGHGOYDCVRUTSU-UHFFFAOYSA-M sodium;2-hydroxypropane-1,2,3-tricarboxylic acid;hydroxide Chemical group [OH-].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O IGHGOYDCVRUTSU-UHFFFAOYSA-M 0.000 claims description 2
JISIBLCXFLGVJX-UHFFFAOYSA-M sodium;butanedioic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CCC(O)=O JISIBLCXFLGVJX-UHFFFAOYSA-M 0.000 claims description 2
SERLAGPUMNYUCK-YJOKQAJESA-N 6-O-alpha-D-glucopyranosyl-D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-YJOKQAJESA-N 0.000 claims 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 8
AAIZYVIMLNQXFI-GRHBHMESSA-L disodium (Z)-but-2-enedioate hydrochloride Chemical compound C(\C=C/C(=O)O)(=O)[O-].[Na+].[Cl-].[Na+] AAIZYVIMLNQXFI-GRHBHMESSA-L 0.000 claims 3
208000019695 Migraine disease Diseases 0.000 claims 2
239000004353 Polyethylene glycol 8000 Substances 0.000 claims 1
229940085678 polyethylene glycol 8000 Drugs 0.000 claims 1
235000019446 polyethylene glycol 8000 Nutrition 0.000 claims 1
XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 abstract description 18
239000007853 buffer solution Substances 0.000 abstract description 2
239000008184 oral solid dosage form Substances 0.000 abstract description 2
239000003814 drug Substances 0.000 description 112
229940079593 drug Drugs 0.000 description 108
239000004615 ingredient Substances 0.000 description 48
238000009472 formulation Methods 0.000 description 43
-1 starch and cellulose Chemical class 0.000 description 32
239000000047 product Substances 0.000 description 28
239000000796 flavoring agent Substances 0.000 description 16
125000000524 functional group Chemical group 0.000 description 16
239000011159 matrix material Substances 0.000 description 16
239000002585 base Substances 0.000 description 15
239000003623 enhancer Substances 0.000 description 15
239000000243 solution Substances 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
229940124630 bronchodilator Drugs 0.000 description 12
235000019634 flavors Nutrition 0.000 description 12
239000008213 purified water Substances 0.000 description 12
238000012360 testing method Methods 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
230000002378 acidificating effect Effects 0.000 description 11
229940060201 actiq Drugs 0.000 description 11
235000019640 taste Nutrition 0.000 description 11
241001465754 Metazoa Species 0.000 description 10
238000012377 drug delivery Methods 0.000 description 10
239000007937 lozenge Substances 0.000 description 10
238000002156 mixing Methods 0.000 description 10
229960004106 citric acid Drugs 0.000 description 9
235000015165 citric acid Nutrition 0.000 description 9
230000000694 effects Effects 0.000 description 8
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 8
239000003826 tablet Substances 0.000 description 8
230000003276 anti-hypertensive effect Effects 0.000 description 7
239000003292 glue Substances 0.000 description 7
239000011777 magnesium Substances 0.000 description 7
239000000463 material Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
229940049706 benzodiazepine Drugs 0.000 description 6
150000001720 carbohydrates Chemical class 0.000 description 6
235000003599 food sweetener Nutrition 0.000 description 6
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 6
239000007788 liquid Substances 0.000 description 6
239000003402 opiate agonist Substances 0.000 description 6
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 6
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 6
150000008163 sugars Chemical class 0.000 description 6
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SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 5
241000282412 Homo Species 0.000 description 5
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229940125717 barbiturate Drugs 0.000 description 5
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FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 4
229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 4
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 4
NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 4
230000002460 anti-migrenic effect Effects 0.000 description 4
HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 4
230000008901 benefit Effects 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
235000021028 berry Nutrition 0.000 description 4
239000003833 bile salt Substances 0.000 description 4
229940077731 carbohydrate nutrients Drugs 0.000 description 4
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MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 4
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239000008121 dextrose Substances 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
235000013355 food flavoring agent Nutrition 0.000 description 4
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210000001035 gastrointestinal tract Anatomy 0.000 description 4
238000002347 injection Methods 0.000 description 4
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JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
150000002632 lipids Chemical class 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
150000007522 mineralic acids Chemical class 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
238000005192 partition Methods 0.000 description 4
235000011007 phosphoric acid Nutrition 0.000 description 4
229960002052 salbutamol Drugs 0.000 description 4
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