Sixth edition
`
`Edited by
`
`Handbookof
`Pharmaceutical Excipients
`
`
`
`Collegium v. Purdue, PGR2018-00048
`
`Purdue 2025
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`Purdue 2025
`Collegium v. Purdue, PGR2018-00048
`
`

`

`Handbook of Pharmacglflqufixqipients
`
`Collegium v. Purdue, PGR2018-00048
`
`Purdue 2025
`
`Purdue 2025
`Collegium v. Purdue, PGR2018-00048
`
`

`

`Handbook of
`
`Pharmaceutical Excipients
`
`SIXTH EDITION
`
`Edited by
`
`Raymond C Rowe BPhorm, PhD, DSC, FRPharmS, FRSC, CPhys, MInsIP
`Chief Scientist
`
`Intelligensys Ltd, SfokesIey; North Yorkshire, UK
`
`Paul J Sheskey Bsc, RPh
`Application Development Leader
`The Dow Chemical Company, MidIand, MI, USA
`
`Marian E Quinn BSc, MSc
`
`Development Editor
`RoyaI PharmaceuticaI Society of Great Britain, London, UK
`
`€34;
`{’4
`\b
`
`APhA
`
`(RP)
`
`Pharmaceutical Press
`
`London - ChIcago
`
`Collegium v. Purdue, PGR2018-00048
`
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`
`

`

`Published by the Pharmaceutical Press
`An imprint of RPS Publishing
`
`1 Lomhelh High Sireel, London SE1 7JN, UK
`l00 South Atkinson Road, Suite 200, Groysloke, IL 60030-7820, USA
`
`and the American Pl'tonnucisls Association
`22 l 5 Conslllulion Avenue, NW, Washington, DC 20037-2985, USA
`
`cg; Pharmaceutical Press and American Pharmacists Association 2009
`
`(RP) is a trade mark of RPS Publishing
`
`RPS Publishing is the publishing organisation of the Royal Pharmaceutical Society of Great Britain
`
`First published 1986
`Second edition published 1994
`Third edition published 2000
`Fourth edition published 2003
`Fifth edition published 2006
`Sixth edition published 1009
`
`Typeset by Data Standards Ltd. Helm, Somerset
`Primed in Italy by LEGO. S.p.A.
`
`ISBN 9?8 0 85369 3’92 3 {UK}
`ISBN 978 1 58212 135 2 (USA)
`
`All rights reserved. No part of this publication may be
`reproduced, stored in a retrieval system, or transmitted in any
`form or by any means, without the prior written permission
`of the copyright holder.
`The publisher makes no representation, express or implied,
`with regard to the accuracy of the information contained in
`this book and cannot accept any legal responsibility or
`liability for any errors or omissions than may be made.
`
`A mtaiogrw record for this book is available from the British Library
`
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`
`

`

`Polyoxylglycerides
`
`PhEu r:
`
`'I
`BP:
`
`Nonproprietory Names
`Caprylocaproyl Macrogolglyceridcs
`Lauroyl Macrogolglycerides
`Linoleoyi Macregolglycerides
`Oleoyl Macrogolglycerides
`Stearoyl Macrogolglycerides
`Caprylouaproyl Macrogolglycerides
`Lauroyl Macrogolglycerides
`Linoleoyl Macrogolglyccridcs
`Oleoyl Macrogolglycerides
`Steamyl Macrogolglyoerides
`USP-NF: Caprylocaproyl Polyoxylglycerides
`Lauroyl Polyoxylglycerides
`Linoleoyl Polyoxylglyccridcs
`Oleoyl Polyoxylglycerides
`Stcaroyl Polyoxylglycerides
`
`Synonyms
`2
`Polyoxylglycerides are referred to as mactogolglycerides in Europe;
`see Table l.
`
`___
`
`Ink!!! '3 Synergy: 0‘ meanness {molsbwififil- _
`
`Ilium
`Synonyms
`Cop loco royl
`lobrosol; mocrogolglycetidotum
`pol-K:
`glycerides
`coprylocoptoies; PEG 400 coprylic/
`cupnc glyoorldes
`“39
`Louroyl polyoitylglycerides
`Gelucire lid/H; hyd
`enoted coconut oil
`PEG 1500 esters; hydrogenated polm/
`polm kernel oil PEG 300 esters;
`moc
`ol
`lycoridorum louroles
`Cam oil
`300 esters; [abrofil
`M2 l25C5; mocrogolglyceridorurrl
`liooleotes
`Apricot kernel oil PEG 300 esters; Lobmlil
`M i944CS; mocrogolglyceridorurn
`oleotes; pegliooLS-oleate
`Goluciro 50/ LB; hydrogenated palm oil
`PEG l500 esters; mocrogolglyceridorum
`slenmtes
`
`Linoleoyl polyoxylglyoericles
`
`Oleoyl polyoxylglycerides
`
`Slooroyl polyoxylglycerides
`
`Chemical Name and CAS Registry Number
`3
`See Table ll.
`
`Empirical Formula and Molecular Weight
`4
`Polyoxylglyceridcs are mixtures of monoestets, dicstets, and
`triesters of glycerol, and monoesters and diesters of polyethylene
`glycols {PEG}.
`
`Caprylncaproyl polyoxylglycerides Mixtures of monoestcrs, die-
`sters, and triesters of glycerol and monoesrers and die-stars of
`polyethylene glycols with mean relative molecular mass bemccn
`200 and 400. They are obtained by partial alcoholysis of
`medium‘chain triglycerides using polyethylene glycol or by
`esterification of glycerin and polyethylene glycol with caprylic
`(octanoicl acid and capric (decanoic) acid or a mixture of
`glycerin esters and condensates of ethylene oxide with caprylic
`acid and capric acid. They ma y contain free polyethylene glycols.
`Enemy! polyoxylglycefides Mixtures of monoesters, diesters, and
`triesters of glycerol and monocsters and diestcrs of polyethylene
`glycols with mean relative molecular mass between 300 and
`1500. They are obtained by partial alcoholysis of saturated oils
`mainly containing triglycerides of lauric (dodecanoicl acid, using
`polyethylene glycol. or by esterification of glycerol and
`polyethylene glycol with saturated fatty acids, or by mixing
`glycerol esters and condensates of ethylene oxide with the fatty
`acids of these hydrogenated oils.
`Linoleayl polyoxylglycefides Mixtures of monoestcrs, diesters,
`and triestcrs of glycerol and monoesters and diesters of
`polyethylene glycols. They are obtained by partial alcoholysis
`of an unsaturated oil mainly containing triglycerides of linoleic
`{cis.cis-9,12-octadecadienoic} acid, using polyethylene glycol
`with mean relative molecular mass between 300 and 400, or by
`esterificacion of glycerol and polyethylene glycol with unsatu-
`rated fatty acids, or by mixing glycerol esters and condensates of
`ethylene oxide with the fatty acids of this unsaturated oil.
`Okay! pobtoxylglycefides Mixtures of monoestcrs, diesters, and
`triestets of glycerol and monoesters and diestcrs of polyethylene
`glycols. They are obtained by partial alcoholysis of an
`unsaturated oil mainly containing triglycerides of oleic {as-9-
`octadecenoic} acid, using polyethylene glycol with mean relative
`molecular mass between 300 and 400. or by esterification of
`glycerol and polyethylene glycol with unsaturated fatty acids, or
`by mixing glycerol esters and condensates of ethylene oxide with
`the fatty acids of this unsaturated oil.
`Steamyl polyoxylglyoeiides Mixtures of monoesters, diesters.
`and triesters of glycerol and monoestcrs and diestets of
`polyethylene glycols with mean relative molecular mass between
`300 and 4000. They are obtained by partial alcoholysis of
`saturated oils containing mainly triglycerides of steatic {octade-
`canoic} acid, using polyethylene glycol. or by esterilication of
`glycerol and polyethylene glycol with saturated fatty acids, or by
`mixture of glycerol esters and condensates of ethylene oxide with
`the fatty acids of these hydrogenated oils.
`
`Structural Formula
`5
`See Section 4.
`
`
`
`[223129-753]
`
`
`Jobl- Il: Chemical names and CAS registry number: of polyeztylglyceddea. .
`
`
`‘ ___ _
`Chemical name
`Home _
`'
`1 _
`_
`CA5 number
`Decontaic acid, mixed monoester: wilh glycerol and octonoic acid: polyloxy-
`Copryiocoproyl polyoxylglyoerides
`[733 98-615 ]
`l,2-ethonediyl], n—hydro—(o-hydro
`. mixed deconoote and octonoate
`louric ocid. diestar with glycerol; poxl;[oxy-l ,2-elhonedlyll, n—[l-oxododecyll—
`tit-[i l exododecylloxy}
`Corn oil, ethoxylatecl; 9,12octodecodlenolc ocid [9E,lZE}-monooster with
`1,2,313ropone1riol
`9-Ociacleceneic acid [92}. monoesiet with 1,2,3-proponotriol; polyioxy-l ,2-
`athonediyll, o-{l9ZJ-loxo9-oclodecenyflm—hydroxy—
`Dialectic acid, cliesier will: glycerol; pol [oxy-l ,2-eihonediyll. evil-
`[9005-08-7|
`oxooclodocyllm-[I l-oxooctadecylloityiv
`
`Louroyl polyoxylglycerides
`
`[57107-95-6]
`
`{271 94—74-7]
`
`Linoleoyl polyoxyl glycerides
`
`[6 1 789-25-1]
`
`Olnoyl polyoxylglyceridae
`
`[68424-61—3]
`
`[9004-96-0]
`
`Steoreyi polyoxylglycerides
`
`[1323~83-7]
`
`557
`
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`5 5 8
`
`Polyoxylglycerides
`“liunclibhal ‘Category
`6
`Dissolution enhancer; emulsifying agent; nonionic surfactant;
`penetration agent; solubilizing agent,- sustained-releasc agent.
`
`7
`
`Ap Iicatians in Pharmaceutical Emulation or
`'l'ee nology
`Polyoxylglycerides are used as self-emulsifying and solubilizing
`agents in oral and topical pharmaceutical formulations. They are
`also used in cesmetic and food products.
`See also Tables III, N, V, VI, and VII.
`
`
`______._. .__.Hpfiw -.
`._._.—__ __._.__._._
`table II: Uses a? mprylmupreyl Wheefldu.
`
`Use
`Concentration
`Retain-Ice _ _
`Dermal route
`104.5%
`1—1 1
`Nasal route
`2—22%
`12, 13
`Oral route
`Capsule
`
`Sublinguol route
`
`10—99%
`10-35%
`
`14—32
`33
`
`'I‘IHO N: Uses of lauroyiWM‘
`is.
`
`Use
`Concentration
`lightens
`Oral route
`Adsorption [tablet]
`Capsule
`
`34, 35
`14, 29, 3 l , 32. 34.
`35—40, 41.4.4
`Melt granulation
`15-50%
`34, 44, d5
`
`_ Spray drying
`(6016
`_ _
`30, 3d, 35
`
`(30%
`60-99%
`
`Tablavt Umaillnoleeylpelyaaylghtaefides.
`_
`_
`
`Use
`Concentration'
`'
`_
`Relereme
`Dermal route 540%
`23
`Oral route
`
`Capsule
`l0—9‘0‘lé
`l6, is, 2161, 47
`
`Tab-lo VJ: Uses of ele'a'yl paiyomylg'lyderides.
`
`Use
`Concentration
`Relation:
`Dermal route 540%
`2
`Nasal route
`8%
`l3
`Oral route
`
`Capsule
`Ill-90%
`l6. _l 3, 26, 31,46, 48, 49
`
`
`Tabla VII: Uses almond pnhroxfiglycetidee.
`
`
`9mm _._R°‘°'°__..m _
`
`.__
`
`Use _
`Oral mule
`Adsor lion [tablet]
`Ca su
`Met granulatiilon
`Spray congeo ing
`Spray drying
`
`(80%
`60—99%
`l5—50%
`95%
`
`(90%
`
`34, 35, 50
`34. 39, 5ln54
`3:, 55—57
`34, 54
`
`Description
`8
`Polyoxylglycerides are inert liquid or semi—solid waxy materials and
`are amphiphilic in character. Caprylocaproyl polyoxylglycetides are
`pale-yellow oily liquids. Laurayl palyoxylglyccricies and stearoyl
`polyoxylglycerirles occur as pale-yellow waxy solids. Oleoyl
`polyoxylglyocrides and linoleoyl polyoxylglyccrides occur as amber
`
`
`
`
`
`oily liquids, which may give rise to a deposit after prolonged periods
`at 20°C.
`
`Pharmacopeial Specifications
`9
`See Tables VIII and IX.
`
`l0 Typical Praperlies
`Solubility
`Caprylocaproyl and lauroyl' polyoxyl'glycerides: dispersible in
`hot water; freely soluble in methylene chloride.
`Linoieoyl and oleoyi' polwxyiglycerides: practically insoluble
`but dispersible in water; freely soluble in methylene chloride.
`Stenroyl polyoxyiglycerides: dispersible in warm water and
`warm liquid paraffin; soluble in warm ethanol; freely soluble
`in methylene chloride.
`Viscosity
`Linoleoy! polyoxylgbtcerides: 70—90 mPas at 20‘C, 2:35 mPa s
`at 40°C for PEG 300.
`
`Oleoyl poiyoxylglycerides: 75—95 ruPa s at 20°C, m35 mPa s at
`40°C for PEG 300.
`See also Section 9.
`See also Table X.
`
`Stability and Storage Conditions
`'I I
`Polyoxylglyceridcs are very stable and inert. However, preventive
`measures against the risk of oxidation or hydrolysis may be taken to
`ensure stability during handling. See Section 15.
`Polyoxylglyccridcs should be preserved in their original contain-
`ers, and exposure to air,
`light, heat, and moisture should be
`prevented.
`
`12 Ineampatihililies
`
`13 Method of Manufacture
`
`l‘olyoxylglycetides are obtained by partial alcoholysis of vegetable
`oils using macrogols, by cstcrification of glycerol and macrogols
`with unsaturated fatty acids, or by mixing glycerol esters and
`condensates of ethylene oxide with the fatty acids of the vegetable
`oil.
`
`14 Safety
`Polyoxylglyccridcs are used in oral and topical pharmaceutical
`formulations, and also in cosmetics and food products. They are
`generally regarded as relatively nonirritant and nontoxic materials.
`Caprj'locaproyl polyoxylglycerfdes:
`LDSD (rat, oral]: )22 mliikg day}.l”l
`Lauroyl poiyoxyiglycerides:
`LDSO (rat, oral]: 32004 mgllltg dayldwl
`
`‘I 5 Handling Precautions
`Observe normal precautions appropriate to the circumstances and
`quantifies of the material handled (refer to manufacturers‘ safety
`information}.
`Polyoxylglycerides are heterogeneous. Owing to their composi-
`tion and physical characteristics, semisolid polyoxylglycerides can
`segregate by molecular weight over time during storage in contain—
`ers,
`resulting in a nonhomogenous distribution.
`In addition,
`semisolid poiyoxylglycerides must. be heated to at least 20°C above
`melting point in order to ensure that all crystallization clusters are
`fully melted. Therefore, it is essential that the entire contents of each
`container are melted to facilitate sample withdrawal or transfer,
`ensuring sample homogeneity.
`For liquid polyoxylglycerides, owing to their composition and
`physical characteristics, partial crysrallization of saturated glycer-
`
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`

`i
`
`ssppaafijfilfimfilod
`
`695
`
`a.
`
`Vail
`
`Cam—flw_WW mm WWW WW
`
`W613 Umm F'h‘Ellr M nan—um Flier 6.0 m
`HIEurM
`UNI-NF}? PhEur Mi
`umz-mr
`1.
`1-
`+
`+
`+
`+
`+
`+
`Idnnriiicufion
`Chm-n
`+
`—
`+
`—
`+
`—
`pain! PC}
`E6 300
`—
`—
`33—33
`—
`—
`—
`PEG 4100
`—
`—
`36-41
`—
`—
`—
`PEG 600
`_
`—
`33-43
`—
`—
`—
`953 1500
`—
`—
`425-415 —
`—
`-
`“was”? or 20%: 1 5":
`PEG 2m
`30-50
`—
`—
`—
`-
`..
`PEG 300
`60-80
`—
`—
`—
`m
`_
`PEG 400
`30-] 'IO
`—
`—
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`fl
`Addvnlue
`42.0
`£10
`$2.0
`$2.0
`$2.0
`$2.0
`Hydroxyl wine
`.
`PEG 200
`EO-I 20
`50-120
`—
`36-85
`—
`—
`PEG 300
`36-35
`140-180
`”0-130
`65-55
`45-65
`45-65
`PEG 400
`170405
`I I’D—205
`60-50
`36—85
`1545
`45-65
`PEG 600
`—
`—
`50-30
`36-35
`—
`—
`PEG I500
`-—
`—
`Sin-56
`36-85
`—
`—
`Iodine value
`62.0
`§ 2.0
`$2.0
`(2.0
`90-110
`90-1 TU
`Maid- Uuin
`‘63
`$6.0
`(£0
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`4.12.0
`4212.0
`Sapnrliflmil'nn val“
`PEG 20D
`2&5—‘285
`2&5—235
`—
`—
`ISO-170
`150-! 70
`PEG 300
`WEI-l9!)
`170-190
`190-204
`79-204
`150-1?9
`150-!70
`P534100
`35405
`85405
`170-190
`73—204
`—
`—
`PEG 6W
`—
`—
`LSD-17D
`79-204
`—
`-—
`F'EG 1500
`--
`—
`3'9-93
`79-204
`—
`—
`Almlina impuritiu
`+
`+
`+
`—
`+
`—
`Fm
`65.0%
`flitfi
`43.0%
`£5.69.
`€3.0‘K
`$3.036
`Elhybneonfdo
`£1
`dug/g
`53mm
`(lug/a
`#1
`6119/
`Dionne
`£1 ppm
`wilting/g
`(Inppm smug/é?
`(I ppm my???
`Sill
`filflx
`$105
`(”3%
`6!.
`QIM
`mmwh
`filo
`$090138
`£10m 50.001
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`$000
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`€0,136
`£0,153
`120. m
`$0.195
`€0.1%_
`£0 1%
`
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`lf
`G 2.0
`
`45-65
`45-455
`
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`
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`
`$2.0
`
`45-65
`45-455
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`
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`Phlur M}
`
`USPS”?!
`
`mm
`(2%
`50-80%
`204%
`(3%
`(1%
`
`Clo - Snark un‘rd
`Cum - WI: acid
`Cm: - linoleicncfl
`Cum -- lindenfc acid
`0»— Nudlidlcocid
`920:1 -= Eicmndc acid
`
`:31;
`(3%
`(5%
`c555
`AID-.5076
`45-53%
`
`! A
`
`ir-9%
`‘6‘.
`I 5-351
`6 2%
`(2%
`(2%
`
`I:f?“£t§§§§§§
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`30-50%
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`4—259;
`
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`
`
`
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`

`560
`
`Polyoxylglycerides
`
`
`Tgybfifwulmmoipdwwlswa_
`.
`.
`_
`"
`__
`Properly
`Co ryloro
`louroyl
`Linoleoyl
`Olooyl
`Slomoyl
`
`phylum!”
`Powlslrwides Weave: mussel»
`Poiroxrlslrcefidu
`—
`4
`4
`4
`-
`14
`_
`_
`..
`_
`--
`14
`—
`_
`13
`1.0
`_
`o. 95
`o95
`_
`
`1 4504.470
`_
`1 .4554 .475
`1 .4554 .475
`
`_
`
`HLB value
`PEG 300
`PEG 400
`PEG 1500
`Relative densily [oi 20"C}
`
`Refractive index [a 20°52;
`
`ides may be observed after long-term storage. In case of crystal"
`lization, heat to 60—70“C before use.
`Polyoxylglyccridcs are hygroscopic. Only heat in a water bath if
`the materials are contained in a sealed glass container or are for
`immediate use. Otherwise, heat in a micr0wavc or convention oven.
`Avoid exposure to excessive and repeated high temperatures [i.e.
`above 100"CJ and cooling cycles.
`To ensure stability during handling, and avoid the risk of
`oxidation or hydrolysis, the following measures should be taken:
`Risk of oxidation:
`o minimize aeration of the mixture {avoid use of highcpeed
`homogenizers];
`o minimize and control the degree of exposure to heat and light:
`I use a nitrogen blanket.
`Risk of hydrolysis:
`o minimize and control relative humidity;
`e do not heat near a source of humidity (cg. water bath].
`
`16 Regulatory Status
`Lauroyl polyoxylglyceridcs and stearoyl polyoxylglycerides are
`approved as food additives in the USA. Included in the FDA inactive
`Ingredients Database [oral
`route: capsules,
`tablets, solutions;
`topical route: emulsions, creams, lotions; vaginal route: emulsions,
`creams}. Oleyl polyoxylglycerides are included in a topical cream
`formulation licensed in the UK.
`
`I 7 Rololocl Substances
`
`18 Comments
`
`See Table XI for EINECS numbers for polyoxylglycerides.
`
`Cop
`
`'I'ohlo Fl: fittECft-numbers For pohroxylghioaridos.
` ___ _
`EINECSnumber
`:urnzbgggmoxylpl—ycar—leegs
`
`243615-41
`lycericles
`277-452-2
`Oleoyl polvoxydglycendes
`270312-1
`
`Stooroylopolyoylghrcerid—as
`? 1 54359-0
`
`olyo
`
`19 Specific References
`1 Bugni A er al. The effect of skin permeation enhancers on the formation
`of porphyrinsIn mouse slrin during topical application of die methyl
`ester ol' 5uminolevulinic acid. I Pbozocbem Microbial B 2006; 33R}.
`94—9?
`2 Ccschel G er al. Solubility and rransdermal permeation properties of a
`dehydruepia nclrostcrone cvclodcctrin complex from hydmphilic and
`lipophilic vehicles. Drug Delft! 2005; 12(5}: 275—280.
`3 Cheong HA, Choi HK. Effect of ethenolamine salts and enhancers on
`the percutaneous absorption of piroxicam from a pressure sensitive
`adhesive matrix. Eur] Phone Sci 2003; 18(2): 149-15 3.
`Jurkovic P at al. Skin protection against ultraviolet induced free radicals
`with ascorhyl palmitate in microemulsions. Eur J Phone Elephant:
`2003; 56(3): 59—66.
`
`*1
`
`Kikwai L er oi. Effect of vehicles on the transdcrmal delivery of
`melatonin across porcine skin in uirro. j Control Release 1002; 83(2):
`30?—31 1.
`Kim J er al. Effect of vehicles and pressure sensitive adhesives on the
`permeation of merino across hairless mouse skin. for J Pharm 2000;
`196F111 105—113.
`Kreilguard M. Influence of microelnulsions on cutaneous drug delivery.
`Bulletin technique Gaflefossé 2002; 95: ?9—100.
`Kreilgaatcl M er al. influence of a microeruulsiou vehicle on cutaneous
`bioequivalence of a lipophilic model drug assessed by microdialysis and
`pharmacodynamics. Pharm Res 2001: 18(5): 593—599.
`Minghetti P at oi. Evaluation of ex m‘w human skin permeation of
`genisrein and claidzein. Drug Delia 2006; 13(6): 411-415.
`Rhee ‘r'S er al. Transdcrmal deliver):r of ketoprofen using microemui—
`sions. int} Pborm 2001; 223(1—2): 161~l?0.
`Zhao X a: el. Enhancement of transdermal deliveryr of theophvlline
`using rnicroernulsion vehicle. in: )1 Pharm 2006; 32?l1-2l: 58—64.
`Dingernansc] e: at. Pronounced effect of caprylocaptoyl macrogolgly—
`cerides on nasal absorption of 15-159, a peptide serotonin iBi'lD-
`recepror agonist. Clio Pbomrecoi Ther 2000: 68(2}: 114—121.
`Zhang Q at of. Preparation of nimodipinevloatled microcmuisiot‘l for
`intranasal trie'livcr)!r and evaluation on the targeting effwicncy to the
`brain. int] Pborm 2004; ZTSH-Z): 85-96.
`Aungst B] at of.
`improved oral bioavailabilitv of an HW protease
`inhibitor using gelucire 44:14 and labraaol vehicles. Bulletin seclusion:
`Goliefossé 1994; 3?: 49-54.
`Chang RK, Shojaei AH. Effect of a lipoidie exeipient on the absorption
`profile of compound UK 81251 in dogs after oral administration. 1'
`Plasma Plum Sci 2004; 7{ 1}: 8-42.
`Cirri M e: oi. Liquid spray formulations ul xibornol by using sell-
`microemulsifying drug delivery systems. in! I Phone 200?; 340(1—2}:
`34—91.
`Dmnitel M and. Formulation and in vino-n: vino evaluation ofpiribedil
`solid lipid micro— and canopnrtielcs. j Microencopsul 2001; 18(3): 359-
`371.
`Devani M et oi. The rmulaificatiun and solubilisan'on propertiea of
`polyglycolysed oils in self-emulsifying formulations. I Pbdrm Pharma-
`ool 2004; 56(3): 307-316.
`Djordjevic L er of. Characterization of ceprylocaproyl mncrogolglycer-
`ides based microemulsion drug delivery vehicles for an amphiphilic
`drug. Int} Plant»! 2004; 27111—2]: [1—19.
`Baposito E et cl. Amphiphilic association systems for amphoteticin B
`delivery. int} Pizarro 2.003; 2600.}: 249-260.
`Hu 2 er al. A novel emulsifier, Lebmsoi', enhances gastrointestinal
`absorption of guntamicin. Life Sci 2001; 69(24}: 2399—2910.
`Ito Y or oi. Oral solid gentamicin preparation using emulsifier and
`adsorlrntq' Control Release 2005; 10511-2}: 23*31.
`Kim H] et oi. Preparation and in vitro evaluation of sclf-microernulsify-
`ing drug delivery.r systems containing idcbenone. Dmg Dev Ind Phone
`2000; 26(5): 523-519.
`Kornmuru TR. er al. Self-emulsifying drug delivery sysuems (SEDDSJ of
`coenzyme Q10: formulation development: and bioavailabiiity assess-
`ment. In: J Pbams 2001; 212(2): 233—246.
`Rama Prasad YV er al. Evaluation of oral formulations of gentamicin
`containing lahrasul in bear-J: dogs. for] Plim12003;263(1-2): 13-21.
`Slice [-1. Zhong M. Preparation and evaluation of scll—microcmulsifying
`drug deliveryr systems {SMEDDSJ containing ntorvastadn. } Pbam
`Pirarmml 2006; 58(9): 1183—1 191.
`Shibata N of al. Application of pressure-controlled colon delivery
`capsule to oral administration of glyevrrhizin in dogs. J' Pharm
`Pbamcoi 2001; 53(4): 441—447.
`
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`20
`
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`
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`
`2‘1
`
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`26
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`27
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`Purdue 2025
`Collegium v. Purdue, PGR2018-00048
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`Polyoxylglycerides
`
`561
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`28
`
`29
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`30
`
`31
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`32
`
`33
`
`34
`
`35
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`36
`
`3'?
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`38
`
`39
`
`4D
`
`41
`
`42
`
`43
`
`45
`
`46
`
`47
`
`Suhramanian N er al. Formulation design of self-microemulsiiying drug
`delivery systems for improved oral bioavailability of celecoxih. Biol
`Plum: Bull 2004; 27(12): 1993-1999.
`Venlratesan N er al. Gelucire 44l14 and Lnbrcsol in enhancing oral
`absorption of poorly absorhable drugs. Bulletin technique Gertefnssé
`2006; 99: 79—88.
`Venkauesan N er al. Liquid filled nanoparticles as a drug delivery tool
`for protein therapeutics. Biomateriulr 2005; 26(34}: 7154—7163.
`Wei L er al. Preparation and evaluation of SEDDS and SMEDDS
`containing carvedilol. Drug Den Ind Pharm 2005; 31(8): 715—2014.
`Yfiksel N er al. Enhanced bioavailabiliry of pimxicam using Gebtcire
`44/14 and Lobrasol: in ultra and in ultra evaluation. Eur J lem
`Biopbann 2003; 56(3): 453—459.
`subljngually
`Shepherd SE er al. Pharmaookinetic behaviour of
`administered S-methoxypsoralen for PWA therapy. Pbotodefimflal
`Pbololmmtmol Pfioromecl 200}; 127(‘1 J: "—21.
`Jannin V at of. Approaches for the development of solid and semivsolid
`lipid—hosed formulations. Adv Drug Deliv Rao- 2008; 60(6): 73%746.
`Chauhan B er al.
`i’teparation and evaluation of glilsenclamide-
`polyglycoliled glycetides solid disPersions with silicon dioxide by spray
`drying technique. Ear ,l Phone: 3d 2005; 26(2): 219-130.
`Almgst B] oi oi. Amphiphillc vehicles improve the oral hioavailability of
`a poorly soluble HIV protease inhibitor at high doses. In: } Pbarrn
`1997;15q1p79-ss.
`Barakat NS. Btodolac‘iiquid-filled dispersion into hard gelatin capsules:
`an approach to improve dissolution and stability of erodolac formula-
`tion. Drug Der:I Ind Photo: 2006: 32(?}: sss—srs.
`Barker SA 2: al. An investigation into the structure and hioavailability
`of ct-tocophetol dispersions in Geluclre 44!“. I Control Release 2003;
`91(3): 477—488.
`Bowtle W. Lipid formulations for oral drug delivery. Pbam: Technol
`En! 2000: 12(9): 20-30.
`l'wanaga K etnl. Disposition of lipid-based formulation in the intestinal
`tract aflects the absorption of poorly water-soluble drugs. Biol Planner
`Bull 2006; 29(3}: 508—512.
`Kane A er al. A statistical mixture design approach for formulating
`poorly soluble compounds in liquid filled hard shell capsules. Bulletin
`technique Gnflefassé 2006; 99: 43-49.
`Khoo SM er al. The formulation of Halofantrine as either non-
`solubilising PEG 6000 or solubilising lipid based solid dispersions:
`physical stability and absolute bioavailability assessment. Int } Photon
`2000; 205(1—2}: 65-78.
`Schamp K er al. Development of an in ultrollrr viva correlation for lipid
`formulations of EMD $0733.
`a poorly soluble.
`lipophilic drug
`substance. Eur J' Pbamt Blophann 2006; 62(3): 227—234.
`Chambin O. Jannirt V. Interest of multifunctional lipid cxcipients: case
`of Goblcire 441’“. Drug Dev Ind Plum 2.005; 31(6): 527-534.
`Yang D et al. Effect of the melt granulation technique on the dissolution
`characteristics of griscohtlvin. in: 1 Plasma 200?; 329(‘1—2): 71—80.
`Dordunoo SK. Sustained release liquid filled hard gelatin capsules in
`drug discovery and development: a small pharmaceutical company‘s
`pottives. Bulletin technique Gottefossé 2004; 9?: 29—39.
`Bravo Gonzalez RC er of. Improved oral hioavailahiliry of cyclosporin a
`in male Wistar rats. Comparison of a School HS IS containing self—
`
`48
`
`49
`
`.50
`
`31
`
`52
`
`$3
`
`$4
`
`55
`
`56
`
`57
`
`53
`
`59
`
`60
`
`dispersing formulation and a microsuSpcnsion. in: } lerm 2002;
`245(1—2]: 143-151.
`Fernéndee—Carhallido A at cl. Biodegradable ibuprofen—loaded PLGn
`microspheres for
`intraarticular administration. Effect of Labmfil
`addition on release in ur‘rro. Int } anmr 2004; 279: 33-41.
`Kang BK er al. Controlled release of paclitaxel from microcmulsion
`containing I’LGA and evaluation of anti-tumor activity in ultra and in
`viva. Int J Flam 2004; 236(1—2): 147.156.
`Gupta MK at all. Enhanced drug dissolution and bulk properties of solid
`dispersions granulated with a surface adsorbent. Pbann Dev Technol
`2001; 6(4): 563—572.
`Craig DQM. Lipid matrices for sustained release — an academic
`overview. Bulletin recnm'qae Gottefossé 2004; 97: 9'49.
`Galal S at al. Study of lit-ultra release characteristics ol' carbamaaepine
`extended release semisolid matrix filled capsules based on Gelucires.
`Drug Dev ind Pkerm 2004; 3003!: (ZN-829.
`Khan N, Craig DQ. The influence of drug incorporation on the
`structure and release properties of solid dispersions in lipid matrices. }
`Control Release 2003; 93(3): 355—368.
`Shimpi 5L er al. Stabilization and improved in viva pedonnance of
`amorphous etoricoxih using Geluelre 50.03. Plum: Res 2005;2(101:
`171?—I734.
`Ochoa L er al. Preparation of sustained release bydropllilic matrices by
`melt granulation in a high~shear mixer. ] lerm Pharm Sci 2005; 8(2):
`132-140.
`Schaefer T. Pelletisation with meltable binders. Bulletin technique
`Gnflefossé 2004; 97: 113—124.
`Sea A er al. The preparation of agglomerates containing solid
`dispersions of diazepam by melt agglomeration in a high shear mixer.
`lot} Pharm 2003; 259(1-2}: 161—1“.
`Passerini N er al. Evaluation of melt granulation and ultrasonic spray
`congealing as techniques to enhance the dissolution of praziquanttl. in!
`fPha'nn 2.006; 319(1—2}: 92—102.
`Gattefossé. Labrasol: CAT—89107. Test to evaluate the acute oral
`toxicity following a single oral administration lLDsol in rats, 1989.
`Gartefossé. Lnlmrfil MZIJGCS: CAT-8815. Test
`to evaluate oral
`toxicity following a single oral administration in the rat [litnir test],
`1983.
`
`20 General References
`Gattefossé. Technical literature: Gslncire W14, 200?.
`Gartelossé. Technical literature: Gelucire 50ll3, 2005.
`Garrefossé. Technical literature: Oral route etttcipients1 200?.
`
`
`
`21 Author
`
`M julien.
`
`22 Date of Revision
`3 March 2009.
`
`Collegium V. Purdue, PGR2018-00048
`
`Purdue 2025
`
`Purdue 2025
`Collegium v. Purdue, PGR2018-00048
`
`