Handbook of
`
`PHARMACEUTICAL
`
`EXCIPIENTS
`
`Second Edition
`
`Edited by
`Ainley Wade and Paul J Weller
`
`The Pharmaceutical Press
`
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`

`

`© Copyright 1986, 1994 by the American Pharmacetttical Association, 2215 Constitution Avenue NW, Washington,
`DC 2003?-2985, USA, and The Pharrnacetitical Press. Royal Phartnaceutical Society of G1'eat Britain, 1 Lambeth High
`Street, London, SE1 TJN, Engiand.
`
`A catalogue record for this book is available from the British Library.
`
`Library of Congress Catalog Card Number: 94—?94‘)2.
`
`International Standard Book Number (ISBN) in the UK: 0 85369 305 6
`International Standard Book Number (ISBN) in the USA: 0 9l?3() 66 8
`
`No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical,
`including photocopy, recording, or any information storage or retrieval system, without prior written permission from
`the joint publishers.
`
`Typeset in Great Britain by Alden Multimedia, Northampton.
`Printed and bound in Great Britain by
`
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`

`Hydroxypropyl
`Methylcellulose
`
`l. Nonproprietary Names
`BP: Hypromellose
`PhEur: Methylhydroxyptopylccllulosum
`USP: Hydroxypropyl methylcellulose
`
`2. Synonyms
`Cellulose,
`ltydroxypropyl methyl ether; Ca.-’.In.umt' MHPC;
`E464; HPMC;
`:".a‘r>rhocc'l; methyleellulose propylene glycol
`ether; methyl hydroxyptopylcellulose; Mr’tot"o.s'c=; P!'a::i‘iimcori.'.
`
`3. Chemical Name and CAS Registry Number
`Cellulose, 2-Hydroxypropyl methyl ether
`[90i]4—65—3]
`
`4. Empirical Formula Molecular Weight
`The PhE1Ir I992 describes hydroxypropyl methylcellulose as a
`partly 0—methylated and O-(2-hydroxypropylated) cellulose.
`It
`is available in several grades which vary in viscosity and
`extent of substitution. Grades may be distinguished by
`appending a number indicative of the apparent viscosity,
`in
`mPa s, ofa 2% vvfw aqueous solution at 20"C. Hydroxypropyl
`methylcellulose defined in the USP XXII
`specifies
`the
`substitution type by appending a four digit number to the
`nonproprietary name, c.g. hydroxypropyl methylcellulose
`I828. The first two digits refer to the approximate percentage
`content of the methoxy group (OCH3). The second two digits
`refer to the approximate percentage content of the hydroxy-
`propoxy group (OCI-I;CHOHCH3}t calculated on a dried
`basis. Molecular weight is approximately 10000-l 500 000.
`
`5. Structural Formula
`
`CH,0R
`
`or:
`
`0
`
`o
`
`D
`
`on
`
`OR
`
`0R
`
`0
`
`cH,ok
`
`Where R is H. CH3 or [CH3CH(OH)CH3].
`
`6. Functional Category
`Coating agent:
`lilm—former; stabilizing agent; suspending
`agent; tablet binder; viscosity—increasing agent.
`
`h"_1-'dn:_r_ij;u'r)p_t-'1’ 391:3f»iiyt'('eH'rrItJ.\'c
`
`229
`
`In oral products, hydroxypropyl melhylccllulose is primarily
`used as a tablet binder," in lilm-c0ating‘3'7' and as an
`extended release tablet r11atrix.‘"'”’ Concentrations of between
`2-5"/1: W,-‘W may he used as a binder in either wet or dry
`granulation processes. High viscosity grades may be used to
`retard the release ol‘ water—solul:-le drugs from a matrix.
`Depending upon the viscosity grade, concentrations between
`2—t0% wfw are used as film-forming solutions to film-coat
`tablets. Lower viscosity grades are used iI1 aqueous film-
`coating solutions while higher viscosity grades are used with
`organic solvents.
`Hydroxypropyl methylcellulose is also used as a suspending
`and thickening agent
`in topical
`formulations, particularly
`ophthalmic preparations. Compared with mcthylecllulose,
`hydroxypropyl irtethylccllulose produces solutions of greater
`clarity, with fewer undispersed fibres present, and is therefore
`prel'erred in fortnulations for ophthalmic use. Concentrations
`of between 0.45-l.{)% wfw may be added as a thickening agent
`to vehicles for eye-drops and artificial tear soiutions.
`Hydroxypropyl methylcellulose is also used as an emulsifier,
`suspending agent and stabilizing agent
`in topical gels and
`ointments. As a protective colloid, it can prevent droplets and
`particles from coalescing or agglomerating, thus inhibiting the
`formation of sediments.
`
`ln addition, hydroxypropyl mcthylcellulose is used as an
`adhesive in plastic bandages and as a wetting agent for hard
`contact lenses. It is also widely used in cosmetics and food
`products.
`
`8. Description
`I-lydroxypropyl rrtethylcellulose is an odorless and tasteless,
`white or creamy-white colored fibrous or granular powder.
`
`9. Pharmaeopeia! Specifications
`Test
`PhEur 1992
`
`Identification
`Appearance of solution
`pH (1% wfw solution)
`Apparent viscosity
`Loss on drying
`Residue on ignition
`for viscosity grade > 50 mPa s
`for viscosity grade 5c 50 mPa s
`for type [828 of all viscositics
`Sulfated ash
`
`Arsenic
`ChloI'idcs
`Heavy metals
`Mcthoxy content
`Type 1828
`Type 2208
`Type 2906
`Type 2910
`Hydroxypropoxy content
`Type [828
`Type 2208
`Type 2906
`Type 2910
`
`.
`
`.
`
`$ 5.0%
`
`5,
`l.5%
`=.-’~. 3.0%
`:4, 5.0%
`-
`
`-as 3 ppm
`—
`S, fl.00| %
`
`16.5-20.0%
`I91}-24.0%
`2'l'.t}—3t].I]%
`23.0-3t].D“/o
`
`23.0~32.0%
`4.0-l2.t}“/u
`4.0-1.5%
`7.{l—l2.0‘3/o
`
`Tr‘. Applications in Pharmaceutical Formulation or
`Technology
`tnethylcellulose is widely used in oral and
`Hydroxypropyl
`topical pharmaceutical Forinulatioiis.
`
`10. Typical Properties
`A ctr!!!)rfrrikrrlfirfry-':
`pH = 5.5-8.0 for a l% wfvv aqueous solution.
`
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`230 Hydro.\‘ypropyt' Metliyiceflttlose
`
`SEM: 1
`Eitcipient: Hydroxypropyl methylcellulose
`Manufacturer: Shin-Etsu Chemical Co Ltd
`Lot No.: 832M
`Magnification: 60::
`voltage: lDkV
`
`.
`
`'
`
`SEM: 2
`Excipienl: Hydroxypropyl mctliylccllulosc
`Manufacturer: Shin-Etsu Cliemicul Co Ltd
`Lot No.: 33214
`Magnification: tatlflx
`
`Vomgc: mkv
`
`Ash: 1.5-3.0%, depending upon the grade.
`Atttoigiifrioii tempcrariu'e: 360°C
`Density (tamiedj: 0.50-0.70 g;'cm3 for P.-'mi'mrrcont.
`Melting point: browns at 190-200°C; cha1's at 225-230°C. Glass
`transition temperature is I70-180°C.
`Moi.rf:tt'e content: hydroxypropyl methylcellulose absorbs
`moisture from the atmosphere, the amount of water absorbed
`depending upon the initial moisture content and the
`temperature and relative humidity of the surrounding air.
`See n.-‘so HPE Data.
`
`Soiubi.iit_v: soluble in cold water, forming a viscous colloidal
`solution; practically insoluble in chloroform, ethanol (95%)
`and ether, but soluble in mixtures of ethanol and dichlor-
`ornethane. and mixtures of methanol and dichloromethane.
`Certain grades of hydroxypropyl methylcellulose are soluble in
`aqueous acetone solutions, mixtures of dichlorornethane and
`propan-2-ol. and other organic solvents. See also Section II.
`Specific g.t'm=i.[i=: 1.26
`Vl".S'IE‘tJ'.t‘fl‘_]'
`(dynmm'c): a wide range of viscosity types are
`commercially available. Aqueous solutions are most corn-
`monly prepared although hydroxypropyl methyleellutose may
`also be dissolved in aqueous alcohols such as ethanol and
`propan—2~o| provided the alcohol content is less than 50% tvfw.
`Dichloromethane and ethanol mixtures may also be used to
`prepare viscous hydroxypropyl
`inethylcellulose solutions.
`Solutions p1'epared using organic solvents tend to be more
`viscous; increasing concentration also produces more viscous
`solutions, see Table I.
`recoinmended that
`is
`it
`To prepare an aqueous solution,
`hydroxypropyl nlethylcellulose is dispersed and thoroughly
`hydrated in about 20-30% of the required amount of water.
`The water should be vigorously stirred and heated to 80-90°C
`then the remaining hydroxypropyl ntethylcellulose added.
`Cold water should then be added to produce the required
`volume.
`When a water—miscible organic solvent such as ethanol. glycol.
`or mixtures of ethanol and dichloromethane is used,
`the
`hydroxypropyl methylcellulose should first be dispersed into
`the organic solvent, at a ratio of 5-8 parts of solvent to 1 part
`of hydroxypropyl methylceilulose. Cold water is then added to
`produce the required volume.
`
`Table 1: Dynamic viscosity (mPa s) of Phummcom 603 {Shin-Etsu
`Chemical Co Ltd) solutions in various solvents at 20"'C.
`
`Solvent
`
`Viscosity (mPa 5) at }.'l}"C
`Concentration (‘l/n nftv}
`2
`6
`10
`14
`
`Dichloromethane: ethanol (50:50)
`Ethanol: water (50:50)
`Water
`
`4
`8
`3
`
`28
`32
`I5
`
`I50
`I20
`45
`
`580
`350
`I00
`
`Moisture content
`Moisture content
`Moisture content
`
`HPE Laboratory Project Data
`Method
`Lab #
`Results
`
`MC-20
`MC—20
`EMC-l
`
`I5
`I5
`IS
`
`_
`
`2.It)% “"
`3.|tJ"/a ”"
`See Fig.
`
`I. ""’
`
`Supplier: a. Dow Chemical Company; b. Aqua Ion.
`
`11. Stability and Storage Conditions
`Hydroxypropyl methylcellulose powder is a stable material
`allliough it is hygroscopic after drying.
`
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`
`
`Percentequilibriummoistureat25°C
`
`40
`
`50
`
`‘F0
`
`Percent relative humidity
`
`Fig. I: Equilibrium moisture content of Iiydroxypropyl nicth_vl-
`cellulose. Methocel EI5 (Dow Chemical Company, Lot No.:
`QP0502-801-E).
`
`Solutions are stable between ])I-[ 3-ll. Increasing ternperatuie
`reduces the viscosity of solutions. Hydroxypropyl niethylce|—
`lulose undergoes a reversible sol to gel
`traii1sfoi'iii:ition upon
`heating and cooling respectively. The gel point
`is 50-90°C.
`depending upon the grade of inziterial.
`Aqueous solutions are comparatively eiizyine-resistant, pro-
`viding good viscosity stability during long-term storagc.“3’
`However, aqueous solutions ai'e liable to microbial spoilage
`and should be preserved with an aiitimicrobial preservative.
`When used as a viscosity-increasing agent
`in ophthalinic
`solutions. benzalkonium chloi'ide is connnonly used for this
`purpose. Aqueous solutions may also be sterilized by
`autoclaving; the coagulated polymer must be i‘e(lispei'sed oit
`cooling by sliaking.
`I-Iydroxypropyl tnetltylcellttlose powder should be stored in at
`well-closed container. in a cool. dry. place.
`
`I2. incompatibilities
`incoinpatible with some
`I-lydioxypropyl methylcellulose is
`oxidizing agents. Since it is nonionic, ltydroxypropyl methyl-
`cellulose will not coinplcx with metallic salts and ionic oi‘gaiiics
`to Forin insoluble precipitates.
`
`13. Method of Manufacture
`
`A pui‘ilied Form oi‘ cellulose, obtained From cotton waste or
`wood pulp,
`is
`reacted with sodium hydroxide solution to
`produce a swollen alkali cellulose which is clietnically more
`reactive than untreated cellulose. The alkali cellulose is then
`treated with chloi'oinelhane aitd propylene oxide to produce
`iiictliylliydroxypropyl ethers of cellulose. The fibrous i'eaction
`product is then purified and ground to a fine, uni|‘orni powder
`or granules.
`
`14. Safety
`I-lydroxypropyl inetliylcellulose is widely used as an cxcipient
`in oral and topical pharmaceutical loi'iiiiilatioiis. It is also used
`extensively in cosmetics and Food products.
`
`H]‘(i!‘rJ.\'_l’jJi"(),')_l’i Meili_i'.-’ce!l‘iil'ri.\'e
`
`23!
`
`inethylcellulose is generally regarded as a
`Hydroxypropyl
`nontoxic and l10l‘lll‘l‘llEl|]l material although excessive oral
`coiisiiinption may have 21 laxative c|Tcci.""’ The WHO has not
`specified an acceptable daily intake for
`l1ydro.\ypropy|
`inetliylcellulose since the levels consumed were not considered
`to represent a liazard to |iea|tI1.”5’
`Lo“, (mouse, IP): 5 gikg“"‘
`LD5i. (rat. II’): 5.2 glkg
`
`15. Handling Precautions
`Observe normal [J1'BC'clLllI0l1S appropriate to the circiimstaiices
`and quantity of material handled. Hydroxypropyl methylce|-
`Iulose dust may be irritant to the eyes and eye protection is
`reconiinended. Excessive dust generation should be avoided to
`minimize the risks of explosions. Hyclroxypropyl inelltylcellu-
`lose is combustible.
`
`16. Regulatory Status
`GRAS listed. Accepted as a food additive in Europe. Inchided
`in the FDA Inactive Ingredients Guide (oplithalmic prepara-
`tions, oral capsules. suspensions. syrups and tablets.
`topical
`and vaginal preparations}. Included in nonparentei'al medi-
`cines licensed in the UK.
`
`17. Pharinacopeias
`Bi‘. Eur, Fr, Gr, It, Jpn, Neth. Poi't, Swiss and US.
`
`18. Related Substances
`
`I-lydroxyethyl Cellulose; Hydi'oxypi‘opy| Cellulose; Hydroxy-
`propyl Methylcellulose Pltthalate.
`
`19. Comments
`
`Powdered or graiitilar, surface-treated grades of liydroxypro-
`pyl methylcellulose are also available which are dispersible in
`cold water. The dissolution rate of these materials can be
`controlled by a shift in pH and they are thus iiseiul for slow-
`i'elease or en teric coated foriiitiizitiotis.
`
`20. Specific References
`l. Chowhan ZT. Role of binders in mois1ui'e—iiidiiccd hardness
`increase in coinpressed tablets and its effect on in i'i‘.'ro
`dlSll'IlCg1‘iI.l.l0l'l and dissolution. J Phiirin Sci I980; 69: I-4.
`Rowe RC. The adhesion of filiri coatings to tablet surfaces — the
`effect of some direct compression cxcipieiits and lubricants. J
`Pltarni Pliarmacol I977; 29: 723-726.
`Rowe RC. The molecular weight and niolcciilar weight
`disli'ibiition of hydroxypropyl
`inctliylcclliilosc used in the film
`coating of tablets. J Pharin Phiirinacol I980; 32: ll6~ll9.
`Banker G. Peck G. Jan 5. Piraikitikulr P. Evaluation ct‘
`hydroxypropyl cellulose and hydroxypropyl methyl cellulose as
`aqueous based film coatings. Drug Dev Ind Pliarin Will; 7: 693-
`Tlti.
`
`incchanisin oi‘
`(')k|1ainal”c A0. York I-‘. M0i5ltIl'U perineatioii
`sonic aqueous-based l'ilin coats.
`.l Pliarm Pharinacol
`I982:
`34(Si1pp|): 53F.
`Aldertnaii DA, Schulz GJ. Method of iniiking a granular. cold
`water dispcrsible coating cotnpoititioii for tablets. US Patent
`48|6298. I989.
`Patcll MK., Taste masking phiirinacctitical agents. US Patent
`49l6|6I. I990.
`Hardy JG. Kcnncrlcy JW. Taylor MJ. Wilsoii CG. Davis SS.
`Release rates from sitstained-rclcasc buccal
`tablets in titan. J
`Pharm Phairinacol I982; 34(Suppl).' 9lP.
`
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`232
`
`H}=di'r2,\'_i*pi'0p_iF! Mc!t'r_vh'r'Htilo.ve
`
`Hogan JE. Hydroxypropylnxcthyrlcclltilose sustained release
`tecliliology. Drug Dev Ind Pharm I989: IS: 975-999.
`Shah AC, Britten NJ, Oianotf LS, Badalamcnti JN. Gel-matrix
`systems exhibiting bimodal controlled release for oral delivery. J
`Controlled Release 1989; 9:
`l69—l?'S_
`Wilson HC. Cuff GW. Sustained release of isomazolc from
`matrix tablets administered to dogs. J Pharm Sci I989; TB: 582-
`584.
`
`Daltl TC. Calderwood T. Bormelh A, Tt'iInble K, Piepnteicr E.
`Influence of pltysicocltentical properties of h)'dI'oxypro])yl
`melltylccllulose on naproxcn release front sustained release
`matrix tablets. J Controlled Release I990: 14:
`|—lii.
`Banker G. Peck G, Williams E. Taylor D. Piralvtitikulr P.
`Microbiological considerations of polymer solutions used in
`aqueous film coating. Drug Dev [nd Pharin [9821 8.‘ 41-5].
`Final report on the safety assessment of hydroxyethylccllulose.
`hydroxypropylcelltilosc, metltylccllulose. hydroxypropyl methyl-
`ccllulose and cellulose gum. J Am Coll Toxicol I986; 5(3):
`l~fit].
`FAOZWI-IO. Evaluation of certain food additives and contami-
`nants:
`llIirly—liftit
`report of the joint FAOIJWI-l0 expert
`committee on food additives. Tech Rep Scr Wld l-Iltlt Org
`I990: No. 789.
`I6. Sweet DV, editor. Registry of toxic effects of chemical
`substances. Cincinnati: US Department of I-lealth. I981‘.
`
`21. General References
`
`Dow Chemical Company. Technical literature: tl‘f(’ffH}t"(’f. I993.
`Doelkcr E. Cellulose derivatives. Adv Polymer Sci I993;
`IUT: I99-265.
`Malalualaris S. Karidas T, Goidas I’. Effect of particle size and sorbed
`moisture on the compression bcltavior ol‘ some hytlroxypropyl
`
`mcthylccllulosc(HPMC}polyn1ers. Int J Pharmaceutics I994; H13:
`205~2|5.
`
`Papadiniitrioa E. Buckton G, Efettlakis M. Probing the II'tL‘Cl1itI'll$l‘t'l5 of
`swelling of hydI'oxypropvlmetl1)*lcellulose matrices. Int J Pharma-
`ceutics I993: 93: 57-62.
`Influence 0|‘ liydroxypropyl
`Par-ah PV. Nayak MP. Ritschcl WA.
`methylccllulose and of manufacturing technique on in w'.'m
`performance of selected antacids. Drug Dev lutl Pharm I985: ll:
`169-185.
`Radebaugh GW. Murtha JL. Julian TN. Bondi JN. Methods for
`evaluating the puncture and shear properties of pharmaceutical
`polymeric Iilms. Int J Pliartnacculics 1988: 45: 39-46.
`Rowe RC. Materials used ill the film coating of oral dosage forms. In:
`Florence AT. editor. Critical reports on applied chemistry. volume
`6: materials used in pharmaceutical t‘orn1ul:ttion. ()x|‘ortl: lilaekivell
`Scientific I-‘ublicatious, I984: l-36.
`Seberl P. Andriauoff N. Rollel M. Elfect of gamma irradiation on
`hyttroxypropylmethylcellulosc powtlers: consequences on pltysical.
`rheological and pharmacotcchuical properties. [nt .| Phartnaceutics
`1993; 99: 3?-42.
`|9??.
`S|1in—Etsu Chemical Co Ltd. Technical literature: .r'Ih’u'fJilr:.\'(*.
`Shin-Etsu Chemical Co Ltd. Technical
`literatitrc: P»‘rar.uirrcorrt
`h).'dI'oxypt'op}'l methylccllulose. I990.
`Wan LSC. Hcug PWS. Wong LF. The effect of Iiydroxypropylmctl1yl-
`cellulose on water penetration into a matrix systexn.
`int
`J
`Pharmaceutics 1991: 73: Ill-l l6.
`
`22. Authors
`
`USA: RJ l-larwood, JL Johnson.
`
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`

`h.=ric.\'
`
`64'}
`
`Gingili oil, 420
`Glidanls,
`Colloidal silicon dioxide, 424
`Magnesium trisilieate. 283
`Powdered cellulose, 88
`Starch, 433
`'
`Talc. SI9
`Trihasic calcium phosphate, 6]
`Ghrctd, 415
`Glucir7c.\', 289, 609, 615, 62]
`L)-Glucitol, 477
`o-(+)-Glucopyranose monohydralc, I54
`4-(ct-o-Glucopyrzmosido)-o-glucopyranosc,
`202
`05-D-GIucopyranosyl—fi—D—frtletofu ra nosidc,
`500
`o--D—G|ucopyrauosyl-I ,4—n—g1t:citol, 288
`4-0-H-D-GIUCopyl‘al‘IOS)']-,8-D-gILlC()]’))’r-
`anose, 202
`Glucose, I54
`Anhydrous, I56
`Liquid, 202
`Syrup, 202
`D-Glucose, 562
`o-(+)-Glucose monohydrate, 154
`1::-Glucuronie acid. 562
`Gluside, 415
`Glyeeridcs, semisyrtlhetic, S I 2
`Glycerin, 204
`Glycerin palmitostearale, 2| I
`Glyeerine, 204
`Glycerol, 204
`Glycerol monostearate, 209
`Se|F—en1ulsifying, 210
`Glycerol palmitostearale, 21 I
`Glycerol polyethylencglycol oxyslearatc, 371
`Glycerol polyelhylencglycol rieinoleate, 371
`Glycerol stearate, 209
`Glycerol lriztcetate, 534
`Glyeeroli monostearas 40-50, 210
`Glycerol~l~oIea1e, 207
`Glyeerolurn, 204
`Glyecryl bcltenate, 2|}
`Glyeeryl monooleate, 207
`Non—emulsifying grade, 207
`Self-emulsifying grade, 207
`Glyccryl mono—oleate, 207
`Culyceryl monopalmitatc, 209
`Glyceryl monostcn rate. 209
`Glyeeryl monostcaratc 40-50, 210
`Glyceryl palmitostearate, 2] l
`Glyceryl stearatc, 209
`Glyceryl stearate SE, 2l0
`Glyceryl lriacctate, 534
`Glyeeryl tribeltenale, 21]
`Glyeeryl tricatprylatefettprate, 299
`GIyceryl—lri-[ I2-Ilydroptystearate), 82
`Gl_t-‘cine max, 482
`Gl'_]-wire sofa, 482
`Glycofurol, 2I3
`Glyeojirrof 75, 213
`Glycoimd grades, 473, 607, 620
`G:'_t=con, 325
`Gt‘)-wort G-700, 204, 607, 620
`Glyeorr S~90, 494. 607, 620
`Gl'yc'o.rper.\'e grades, 375, 607, 620
`Glyeuronan polymer, 10
`GMS, 209
`GMS SE, 210
`Goat's thorn, 532
`Gold, 126
`Go.rs_1'pitmt !'u'r.m.'u.-H, I37
`Grain alcohol, 7
`
`(.ir7‘fl'l'l'ltL:'I(‘, 614
`Grmtulating agents.
`Acacia,
`I
`Dextrose, I54
`Gelatin, I99
`Povidone, 392
`Starch. 483
`Sucrose, 500
`Tragaeanth. 532
`Grmmli'te, 603
`Grape sugar, [54
`Green F, I27, 128
`Green SS, [28
`Grace, 325
`Gram!’ 400, 379
`Grormd G}’fJ.\‘Il'l'i|'1 1-‘G200, 603
`Gromid G_t=p.wmI Supeijfirre I-Write, 603
`Groundnut oil, 329
`Guanine, I29
`Guztr flour, 2l5
`Guar gum, 2l5
`Guethol, 184
`L-Gulo-D-lnannoglyctlronan, I0
`o--(l—-4)-L—Gu|osyluronic acid, I0. 409. 428
`Gum,
`I
`Acacia.
`1
`Arabic,
`Dragon, 532
`Guar, 215
`Hog, S33
`Talha,
`I
`Tragacanth, S32
`Gypsum, 66
`Anhydrous. 66
`Dried, 68
`
`Halite, 44]
`Haloearbon |52a, 169
`Hrtloii 72, I60
`Hard capsules, 199
`Hard (at, 512
`Hard water, 548
`Hard wax, 327
`Hrmo.-‘mi, 264, 604, 617
`HCFC 22, H9
`Heavy kaolin, 247
`Heavy liquid pelrolalum, 3I4
`Heavy magnesium ca rbonatc, 274
`Heavy magnesium oxide, 273
`l-Ieavy mineral oil, 3l4
`HEC‘, 219
`Heliudone pink CN, I27, I28
`Hei'rue.vetri.s', 4] 5
`Hexadeeanoic aeitl, 496
`lsopropyl ester, 245
`l—Metl1ylelhyl ester, 245
`l—I-lexadecanol, 99
`He:-tadecan~l-ol, 99
`u-Hexadceyl alcohol, 99
`Hexadecylic acid, 496
`Hexacleeyltrimcthylammonium bromide, 96,
`97
`Hexadccyltrimethylammonium hydroxide,
`96
`(E,E]-Hexa-2,4-dienoic acid, 470
`Potassium salt, 390
`2,4-Hcxadicnoic acid, 470
`Potassium salt, 390
`Hexallydrothymol, 304
`l, I’—Hexarnetl1ylencbis[S—(4-chloro-
`pheuyl)biguanidc], I06
`Diacetate, I08
`Diglttconatc, I09
`Dihydrochloride, 109
`
`Hcxantie acid, 447
`l,2,3,4,5.6—Hexanel1exoI, 294, 477
`HF/\ 1342!, S24
`HFC l34a. 524
`I-[PC |52a. I69
`Hr71ir'l'wt.s', 109
`Hi'br'scrtrb. 109
`llibitarre, 109
`Hibitrme rtlirrcetate, [08
`High fructose syrup, I95
`Hodug, 617
`Hark.-g DGS, 379
`Haring GMO, 207
`Honing GM S, 209
`Hmiag GMS—D, 210
`Hodrtg PEG, 355, fiI7
`Hodag POE (40) MS. 379
`Hmlrig PSMIL-4, 375
`Horlrig PSMIL-21’), 375
`Hodttg PSMO-5, 375
`Hodag PSM0-20, 375
`Hodag PSMP—20, 375
`Hodrig I-‘SMS—4'. 375
`Horkig PSMS-20, 375
`I-Ior.-‘rig PSTO-20, 375
`Haring PS TS—20, 375
`Hridug 20-S, 379
`Hodug 22-8, 379
`Horlrtg 40-S, 379
`Hodrrg 42-5, 379
`Hodrig 60~S, 379
`Hodttg 62-S, 379
`Hodtrg Hit’!-S, 379
`Hodrrg 154-3, 379
`Hodrrg 600-3, 379
`Hodrrg 602-5’, 379
`Htrdtig SML, 473
`Horfrig SMO, 473
`Hodrtg SMP, 473
`Horlrrg SMS, 473
`Hodrig SS0, 473
`Hodag STO, 473
`Hodrtg S TS, 473
`llog gum, 533
`HPMC, 229
`HPMCP, 233
`HSA, 5
`Human serum albumin. 5
`Humeetants.
`Glycerin, 204
`Propylene glycol, 40?
`Sorbitol, 477
`Triacelin, 534
`H_]'(rdcl'l, GI3
`H_1'mm‘me 7622, 30. 607
`Hl'(lJ7!l7l€ 3500, 27, 607
`I-lyriogeri, 606
`Hydex, 477, 607, 620
`Hydrated aluminum silicate, 247
`Hydrazine yellow, [33
`Hydrochloric acid, 2I7
`Concentrated, 217
`Dilute. 218
`Diluted, 218
`‘Hydrogen oxide, 546
`Hydrogenated Castor oil, 82
`I-Iyd rogeuated castor oil POE—40. 37l
`Hydrogenated Castor oil POE—60, 37!
`Hydrogenated cottonseed oil. 544
`Hydrogenated glucose s)’Wl3- 237
`Hydrogenated maltose. 233
`Hydrogenated palm oil. 544
`
`Mylan v. Qualicaps, |PR2017—OO203
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2003 - 7/7
`
`