ZA200405655B - Formulation and dosage from for increasing oral bioavailability of hydrophilic macromolecules. - Google Patents

Info

Publication number

ZA200405655B

ZA200405655B ZA200405655A ZA200405655A ZA200405655B ZA 200405655 B ZA200405655 B ZA 200405655B ZA 200405655 A ZA200405655 A ZA 200405655A ZA 200405655 A ZA200405655 A ZA 200405655A ZA 200405655 B ZA200405655 B ZA 200405655B

Authority

ZA

South Africa

Prior art keywords

formulation

dosage form

present

bioavailability

hydrophilic macromolecule

Prior art date

2001-12-19

Links

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• 239000000203 mixture Substances 0.000 title claims description 446
• 238000009472 formulation Methods 0.000 title claims description 407
• 229920002521 macromolecule Polymers 0.000 title claims description 70
• 230000001965 increasing effect Effects 0.000 title claims description 16
• 239000002552 dosage form Substances 0.000 claims description 154
• 239000012528 membrane Substances 0.000 claims description 98
• 238000013270 controlled release Methods 0.000 claims description 90
• 229960003820 pentosan polysulfate sodium Drugs 0.000 claims description 85
• QUCDWLYKDRVKMI-UHFFFAOYSA-M sodium;3,4-dimethylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1C QUCDWLYKDRVKMI-UHFFFAOYSA-M 0.000 claims description 85
• 230000003204 osmotic effect Effects 0.000 claims description 76
• 238000011065 in-situ storage Methods 0.000 claims description 75
• -1 polyoxyethylene Polymers 0.000 claims description 53
• 230000004888 barrier function Effects 0.000 claims description 51
• 239000003961 penetration enhancing agent Substances 0.000 claims description 42
• 239000008389 polyethoxylated castor oil Substances 0.000 claims description 41
• 239000002775 capsule Substances 0.000 claims description 38
• 230000002496 gastric effect Effects 0.000 claims description 38
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 34
• 210000001035 gastrointestinal tract Anatomy 0.000 claims description 30
• 239000000499 gel Substances 0.000 claims description 29
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 28
• 229920002685 Polyoxyl 35CastorOil Polymers 0.000 claims description 28
• 229920000669 heparin Polymers 0.000 claims description 28
• QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 claims description 28
• 239000000227 bioadhesive Substances 0.000 claims description 24
• 239000007903 gelatin capsule Substances 0.000 claims description 20
• 239000003055 low molecular weight heparin Substances 0.000 claims description 19
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• 239000002736 nonionic surfactant Substances 0.000 claims description 17
• GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 claims description 16
• 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 14
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 14
• 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 14
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• LDVVMCZRFWMZSG-UHFFFAOYSA-N captan Chemical compound C1C=CCC2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C21 LDVVMCZRFWMZSG-UHFFFAOYSA-N 0.000 claims description 6
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• 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 4
• RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 4
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• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 4
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• ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 4
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• 239000000194 fatty acid Substances 0.000 claims description 4
• 229930195729 fatty acid Natural products 0.000 claims description 4
• 229940075507 glyceryl monostearate Drugs 0.000 claims description 4
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 4
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 4
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