REVIEW ARTICLE
`
`Compendium of Excipients for Parenteral Formulations
`
`MICHAEL F. POWELL, TUE NGUYEN*, and LISA BALOIAN
`
`Pharrm:rcear.l‘r'caI Research and Development, Geueritechy Inc. Sarrttlr San Frarrcisco, California
`
`Overview
`
`The Selection of excipients in parenteral formulation
`design is often both rational and empirical. It is rational in
`the sense that certain types of excipicnts are added to alter
`the formulation properties: it buffers of appropriate pl<a are
`added to control hydrogen ion concentration at a desired pi-l_.
`ii) tonicifiers are added for biocornpatibiiity, iii} surfactants
`are added when necessary to prevent aggregation, adsorp-
`tion to surfaces. or increase solubility, iv) antioxidants are
`included to prevent unwanted oxidation of the drug, and so
`on. The inclttsion of various classes of fomtulation compo-
`nents, and the concentration used is often quite rational, in
`that their behavior and properties are known. and they are
`added to prevent specific problems that would arise in their
`absence. On the other hand, however, the selection of the
`exact excipient used is far from rational; it is empirical in the
`first order, satisfying only one question, “Has it been used
`previously in a similar parenteral formulation?"
`Many prototype formulations have been terminated be-
`cause one or more of the selected excipicrtts was not found
`in a previously approved parenteral product. In fact, there
`have been a handful of cxcipients with striking favorable
`properties, such as trehalose with its ability to confer solid
`state stabilization of several types of proteins, or EDTA and
`its antioxidants by rnetai
`ion chelation. These excipient
`compounds. and many others, have not been used widely.
`largely because of concerns with unknown toxicity, contin-
`ued production supply, or cost.
`Thus,
`the formulation scientist
`
`is often faced with a
`
`dilemnta—which excipients are truly available for use
`(based on what has been used previously), and which are
`not? For example, PEG 400 has been added to several
`parenteral formulations, but what about PEG 1200, or PEG
`4000‘? And at what concentrations, and by what route?
`Sodium citrate is an excellent buffet‘ for many formulations
`at 5 mM, but is too painful in most instances for subcutane-
`ous use at 50 mM. I-[igh concentrations of propylene glycol
`may be used in a slow intravenous infusion, but would
`produce unwanted hemolysis and pain if given by subcutane-
`ous or intramuscular injection. It is often the case that the
`“safe level” of an excipient may depend on the route of
`adrn.inistt'ation. Thesc are only a few examples of factors
`which must be considered when designing a formulation;
`there are dozens more based on empirical
`information
`required for efficient formulation design. but
`thus far a
`
`compendium has not been published. This review was
`written to fill this void.
`
`Herein are listed the excipients found in most of the
`approved and marketed parenteral formulations. given sys-
`tematicaliy by excipient name. In this format it is easy to
`determine what concentrations were used,
`the route of
`administration,
`the main rationale for addition of that
`
`cxcipient, the drug that was formulated, the mar1ufactI.11‘cr_.
`brand name, etc. The information found in this table comes
`
`from several sources, including package inserts, the Physi-
`cian's Desk Reference {PDR "97), as well as personal
`correspondence from the companies supplying the products.
`The published excipiettt concentration was often given in
`different units,
`including:
`rng;"rnl_.,
`:r10s_. Molar, sodium
`equivalents, biological Units, Molal, weight percent. etc.,
`and provided one of tl1t: greatest challenges in putting this
`compendium together. We sought to list all the excipients
`(where possible) in common units (i.e., m_g!mL), so that a
`rapid comparison of the different formulations could be
`made at a glance. (This is not easy to do, for example, when
`comparing Tween 20 concentrations at 0.000] M, 0.01 ‘Yr: and
`1
`rngi’rnL;
`fortunately,
`the average molecular weight
`is
`known for most cxcipients, permitting a standardization of
`excipient concentrations}. This standardization of excipient
`concentrations is perhaps the greatest value of this compen-
`dium, but also represents one of the greatest sources of
`potential error. The recalculation of cxcipient concertrra—
`Lions, often from scant or nondcscriptive data, is not trivial
`and there may be an occasional discrepancy despite cross-
`cliccking with the original
`sources.‘ Nevertheless,
`this
`compendium represents a comprehensive survey of paren-
`teral excipicnts used today, and is a resource for the
`parenteral formulation scientist.
`
`Notes
`
`In putting together this excipient compendium. there were
`a number of points that should be noted, so that the reader
`understands the limitations and assumptions in some of the
`calculations.
`
`1) Concentrations are listed in weight:’volun1e% unless
`otherwise noted. In some cases values are listed in volume!
`
`volume“/n or the manufacturer did not specify what kind of
`percentage they were using (_and in this case it was assumed
`weighdvolume 96}.
`2} Sterile water for injection is included in the excipient
`list when used in solution formulations; however, in most
`
`Received February 16, I998.r'\cccptcd for puhlicaI.iort.l1Inc 1, £998.
`*Author to whom correspondence should he addressed.
`
`them to nguyen.rue@gene.coni for
`‘If discrepancies are found, e-mail
`correction to subsequent compendiums of this nature.
`
`238
`
`
`
`PDA Joumai of Pharmaceutical Science & Technology
`
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 1
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 1
`
`

`

`cases the quantity or percentage of water in the formulation
`was not indicated by the manufacturer or identitied only as
`q.s. We have kept the same conventions here.
`3)
`lixcipients listed are present in the drug formulation
`itself, and do not include excipients present in diluent (for
`example, when a lyophilized formulation is diluted with
`bacteriostatic water containing benzyl alcohol).
`In some
`cases, a diluent is supplied that contains several additional
`excipients and,
`in the case or provided diluent,
`these
`excipients are listed in the excipient category and designated
`with a “I)" in addition to their usual excipient type {the D
`stand for present in diluent).
`4) If no excipients are listed. it means that no exeipients
`were revealed by the manufacturer. In some cases. this is
`because there are no excipients in the formulatiort, but this
`should not be assumed.
`In some cases,
`there may be
`exeipients present but the manufacturer has not disclosed
`them to us, largely for proprietary reasons. Specific follow-
`up about these drugs should be referred to the manufacturer.
`5) The given drug concentration is usually the concentra-
`tion of the compound listed in the drug name category,
`unless identified as otherwise. For example, many drugs are
`formulated as salts such that the salt name is listed in the
`
`drug name category (for example, mitoxantrone hydrochlo-
`ride).
`Ilowever,
`in the drug concentration category,
`the
`concentration of the active component is usually listed (for
`example, equivalent to 2 mgjml_ mitoxantrone free base), so
`as to have a correct concentration of the active drug form.
`6) Vlfhen concentrations of exeipients and drugs are listed
`as a range it
`implies that
`these values could only be
`approximated. Frequently, a range is given because the
`product is available in a variety of storage containers. or
`having several dilution schemes. The ranges given are
`approximations only, based on the available information. In
`no way should these ranges be assumed to encompass all
`possible dilution schemes or eonfigtnations.
`7) P1'eservatives t such as benzyl alcohol) that are present
`only in one configuration of a drug (for example in the
`multiple—dose product, but not
`in the single—use product)
`may be listed as a range [{}—x%). This was to avoid making
`two or more records for essentially the same product
`configuration.
`8) For drugs that are given as a salt form, the counter ion
`may not be listed as an excipient. To search for counter ions
`{like sodium or potassium) one may look in the drug name
`fields (where the entire salt
`is often listed) or
`in the
`
`comments section (where the quantity of the counter ion per
`gram of drug is often provided) as well
`in the excipient
`section.
`
`9) If a pH value is listed for a lyophilized product, in most
`cases, it is the pH of the drug after its initial reconstitution
`with diluent. not the pH at lyophilization.
`10) The concentration values given for excipients and
`active drug product in lyophilized products are usually those
`present at the initial 1'cconstittttion step, and are not necessar-
`ily thc concentrations present at delivery t’_ often further
`dilution occurs). This applies to solution formulations as
`well. Further, excipient concentrations may not take into
`account additive effects from the diluent (for example, a
`drug containing sodium chloride and reconstituted with
`0.9% Sodium Chloride usually lists the concentration of
`sodium chloride present in the undiluted state).
`I I) When the excipient concentration is calculated for a
`Iyophilized product, it is usually done by dividing the weight
`of the material by the volume of liquid added. Note that this
`does not take into account the additive volume of mixing
`that occurs, so such values are to be considered only
`approximations. In cases where the manufacturer provided
`the total volume after mixing, this final volume was used for
`calculations.
`
`12) For drugs requiring reconstitutionldilution, in most
`cases a diluent recommended by the manufacturer is identi-
`fied. In cases where multiple compatible diluents are pos-
`sible. or when dilution schemes are complicated, one will
`see the note “Consult PDR for appropriate dilution." In
`some cases, often when the recommended diluent is pro-
`vided, the manufacturer would not reveal the identity of the
`diluent for proprietary reasons.
`13) Finally, most of the entries herein have been sent to
`the manufacturer for their correction and final notes. Many
`manufacturers participated in checking the data; others did
`not. We want
`to make this compendium as co1'reet as
`possible, and so if errors are found, please e-mail them to
`nguyen.tue@gene.com for correction.
`
`Acknowledgments
`
`This compendium would not have been possible without
`the diligent work of Milianne Chin. She compiled much of
`the data, engineered the database, and contacted dozens of
`different companies to ensure that the listings are up to date.
`
`Vol.52. No.5 I September—0ctober1998
`
`239
`
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 2
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 2
`
`

`

`EXCIPIENTS FOR PARENTERAL FORMULATIONS
`
`Storage
`Dosage
`Manufacturer
`Brand Name
`Drug Name
`pH where Administration
`Conn.
`Excipient
`
`
`
`
`FormRouteapplicable%W!V Container
`paravertcbral
`sarracenia
`Sarapin
`High Chemica!
`Solution
`|'l'll|-llldclsc vial
`purpurea. pitcher
`Company
`plant distillate
`Provides Rose's
`recommended daily
`intake of essential
`Old ‘I‘uben:u1irt
`
`6.0 - 10
`
`1V - intraverlous
`
`5.4% Nephrmnine “
`
`RSLD Laboratc-fies
`Iltc.
`
`Solution
`
`glass container,
`
`acacia
`
`7' .0
`
`it) ~ intradermal
`
`'lubett'-ulin. Old. Tine Test
`
`bcderle Laboratolies
`
`Solution
`
`disposable
`
`acacia (gum arabic)
`
`1‘ .0
`
`ID - intradom1aI
`
`tuberculin, pturilied {PPD) Tine Test
`protein derivative
`
`Letlede Laboratories
`
`Solution
`
`l'l'l1.illi]:Ilt~p1.||'|c.[um
`
`acetate
`
`acetate
`
`acetate
`
`0.059
`
`4.0
`
`IV - intmverto-us
`
`neutral
`
`SC — stlhculancnus
`
`neutral
`
`SC — subwtaneous
`
`acetic acid
`
`0.435
`
`IV - intravenous
`
`fiigrastim
`[recombinant
`Il1Ctl1iOl'W'l human
`L!1'|t:(R) human
`insulin zinc
`susoension
`I..enln(L)Ptn1'ficd
`Pork Insulin Zinc
`Stlapensiort. USP
`riln-drinc
`hydrochloride
`
`‘Ncupc-gcn®
`
`Amgen, Inc.
`
`Solution
`
`single dose vial
`
`Novolin to L
`
`Nova Nortctislt
`Phatruaoeulicals
`
`Suspension
`
`vials
`
`Lcnlc (L) Purified Pork
`Insulin Zinc. Suspension.
`
`Nova Nordislr
`Pharmaceuticals
`
`Suspension
`
`viala
`
`Yntnpar
`
`Astra USA, Inc.
`
`Solution
`
`vial
`
`acetic acid
`
`acetic acid
`
`3°95‘ “id
`
`acetic acid
`
`acetic acid
`
`SC — subcutaneous
`
`lcuprolide acetate
`
`Luprort Injection
`
`TAP
`Pharmaceuticals
`
`Solution
`
`rnultidoae vial
`
`that - intramuscular
`
`calrsitortimsolmon Calcimlr GD injection;
`Svnthelic
`
`R.l1oncvPuuIonc
`Rorcr
`
`W -
`
`'If|||'*1VEI'JtJIl-1
`
`albumin (human).
`25%
`
`Ailaumitiar ti)-25
`
`6.9 = 0.5
`
`W — intravenous
`
`albumin (huinan)
`5%
`
`Albumimr ®—5
`
`Anmur
`Pharmaceutical
`
`Annour
`Pharmaceutical
`
`Solution
`
`Solution
`
`vials
`
`vials
`
`Solution
`
`bottles
`
`3.5 - 5.5
`
`IV - intravenous
`
`vincriatine sulfate, Oneovin {El
`US!‘
`
`Eli Lilly .& Company
`
`Solution
`
`llurnazenil
`
`Romaziccn W
`
`Roche Laboratories
`
`Solution
`
`vials
`
`viais
`
`acetic acid
`
`acotic acid
`
`CLDI
`
`-4.0
`
`1\" - intravenous
`
`Q5 twrw}
`
`SC — subcutaneous
`
`acetic acid
`
`0.46
`
`3.0 - 4.5
`
`N - intravenous
`
`goseretin acetate
`implant
`
`Zoladclt no
`
`mitcxanttonc
`hydrochloride
`
`Novantmnc
`
`?.-aneoa
`Pliarmaceuticals
`
`lmmunex
`Corporation
`
`Solid Implant
`
`disposable
`
`Solution
`
`rttultidose vials
`
`acetic acid
`
`acetic acid
`
`acetic acid
`
`acetic acid
`
`2.5 - 4.5
`
`IM - intramuscular
`
`oxytocin
`
`Oxytocin Injection
`
`Wyeth-Ayers!
`
`Solution
`
`sletili: cartlirlge
`
`[M v intramuscular
`
`promethazine
`hydruchlurldn
`
`Phenergan Injection
`tamnulsl
`
`Wyeth-Ayerst
`
`Solution
`
`arnpuls
`
`IM - intramuscular
`
`~53
`
`IM — intramuscular
`
`promelhazine
`hydmoiticride
`
`nensligrrtina
`methylaulfate
`
`Phenergan Injection
`
`Wyeth-Ayers!
`
`Solution
`
`sterile ca.rn"idg=
`
`Pioatigmin Irijectable
`
`ICN Phsnnacculicala
`
`Solution
`
`multiduse vial
`
`acclic acid
`
`0.2 25
`
`IM - i.ntramuac1lIar
`
`calciranin-aalmon Miwalcin ®
`
`Sandoz
`Pharmaceuticals
`
`solution
`
`vial
`
`acetic acid
`
`acetic acid
`
`6.4 - 12
`
`IN! - intramusculat
`
`4:0
`
`N - intravenous
`
`tetanus immune
`globulin (human)
`onmatilv Iv.-Z}
`rocurortium
`bromide
`
`1-1)-‘pet-Tet ®
`
`Bayer
`Corporation-Bit:-[ogi
`
`solution
`
`prefillud
`
`Zenturon 7" Injection
`
`Orgarton
`
`Solution
`
`multiduse vial
`
`acctic acid (ampul)
`
`IM - intramuscular
`
`leuprolide acetate
`
`Lupron Depot 7.5
`
`acetic acid {glacial}
`
`0.2
`
`-1.2 : 0.3
`
`|\-" - intravenous
`
`octreotide acetate
`injection
`
`Sandnstatin E
`
`‘II.-\P
`Pharmaceuticals,
`
`Sandoz.
`Pltarmacculicals
`
`Lyopttilized
`
`single dose vials
`
`Solution
`
`arnpuls
`
`240
`
`FDA Journal of Pharmaceutical Science 8. Technology
`
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 3
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 3
`
`

`

`Exclpient
`
`acetic acid N1‘
`
`aoelic acid NF
`
`acelonc sodium
`
`acetone sodium
`
`acetone sodium
`
`aoelone sodium
`
`alanine
`
`albumin
`
`albumin
`
`alhumin {nun-um)
`
`llI3ul'l'tI1'I_{_I1l.u'r|,an}
`
`EXCIPIENTS FOR PARENTERAL FORMULATIONS
`
`Conc.
`%W.I'\r'
`
`pH where
`applicable
`
`nttminlstratinn
`Route
`IM - inlramu scular
`
`Drug Name
`
`Brand Name
`
`Manuiacttl rer
`
`leuprolide acetate
`
`Lupron Depot-Ped
`
`1M - inlrnmusclrlar
`
`oxytoci n
`
`Syntocinon ®
`
`Dosage
`form
`
`Storage
`Container
`
`Lyophilized
`
`single dose via!
`
`TM‘
`Pharmaceuticals
`
`Santloz
`
`IM - intramuscular
`
`pentazrocine lactate
`
`Talwin Injection
`{cartridge needle]
`
`Sanofi Winthrop
`
`Solution
`
`carltidgo needle
`
`Inultidose vials
`
`ampuls
`
`ampuls
`
`IM - intramuscular
`
`pt.-ntazocine lactate-
`
`Talwirt injection
`{multidose vial}
`
`Sanofi Winthrop
`
`Spinal ancslhcsia
`
`spinal anesthesia
`
`IV - intravenous
`
`procaine
`hydrochloride
`
`letraoaine
`Itydmchloridc
`
`antiljtrombin Ill
`{hum an}
`
`IV - intravenous
`
`epuctin alfa
`
`Novocein
`
`Sanofi Winthrop
`
`Pontocaim Hydruchluridc
`Hi Solution
`
`Sanofi Winthrop
`
`Thrcmhnta III 09
`
`IM v intramuscular
`
`lmavax G3 Rabies Vaccine
`
`lV~i.nt.ravenot.ts
`
`I\’—inI:at-enous
`
`-
`
`intravenous
`
`Bayer
`Corporation-Biologi
`
`Ont-to Biolv.-ch, Inc.
`
`Conna Light
`Laboratiea Inc.
`
`Armour
`Phannacculical
`
`Baxter Heallhcare
`Corporation
`
`Lyopltitiited
`
`single dose vials
`
`single dose vial
`
`single dose vial
`
`Lyopltilized
`
`single-dose
`
`Lyophilized
`
`single use hotiles
`
`single dose vial
`
`rabies virus
`prepared from
`strain
`Anlihcrrtophilic
`Factor
`{recorn binantl
`Immune Glohulln
`Intravenous
`(human) (]0‘I\"'I
`antihcrnuphilic
`factor
`(recon: binant}
`antihem ophllic
`factor (Human)
`
`anlihem ophilic
`factor
`[recombinantl
`bolulirtum toxin
`type A
`
`utokinase for
`injection
`
`cpootin alfa
`[recombinant
`htttnan
`epoelin alfa
`(recombinant
`human
`
`irnmun-t: globulin
`IV"(IItIn1nn}
`prlmaruv Igfi
`monoclo nll
`antibody purified
`human
`interferon beta—lb
`
`cylomegatovirus
`immune globulin
`intravenous
`poliovtrus vaccine
`inactivated; type I
`(Mahoneyl. tyne 2
`interferon alfa-2a.
`recombine nl
`
`inlnwcnous
`
`- intravenous
`
`- in Lramunculnr
`
`intravenous
`
`intravenous
`
`i.ntrnve:1ous
`
`intravenous
`
`intravenous
`
`IV - intravenous
`
`IM - intramuscular
`
`Helixate "4
`
`Bayer
`Corpo ralion-Biologi
`
`Bayer
`Co rporalion-Blologi
`
`Armour
`Pharmaceutical
`
`Ly ophillzed
`
`Lyophilized
`
`single dose bottle
`
`I..yophilizcd
`
`single dose
`
`Allergen Inc.
`
`L)-uphiiiited
`
`ampuls
`
`Abbokinase
`
`Abholt Laboratories
`
`Ly ophitizcd
`
`I-Ipogen {I9
`
`Amgen, Inc.
`
`Solution
`
`fiihglc dose vial
`
`Epogcn CD - rnttllidusz
`
`Amgen. Inc.
`
`multidose vial
`
`Arrnour
`Phannaoeutical
`
`Armour
`Pharmaceutical
`
`Lyophilizcd
`
`single dose vials
`
`Lyuphilized
`
`single dose vial
`
`Monoclnte-P IE Factor
`VIII: C PartaI.u'j:zed
`
`Retaseron ti:
`
`Belle; Laboratories
`
`Ly ophi Iized
`
`single use vial
`
`Cytofiam IE.‘
`
`Poliovax CD
`
`Med] mrrrune, Inc.
`
`Sterile Liquid
`
`single dose vial
`
`Contra ught
`Laboratories, Inc.
`
`Suspen sion
`
`nropoutes
`
`Rufepon E-A
`
`Roche Laboratories
`
`Solution
`
`albunlin (mmm,
`
`al'bum.iI‘I (human)
`
`all:-tttllttt thumg.-1}
`
`albumin {human}
`
`albumin (human)
`
`albumin (human)
`
`albumin (human)
`
`albumin (human)
`
`albumin [hut-nan}
`
`albumin (human)
`
`aibumin {human}
`
`albumin {nu mm}
`
`albumin {human}
`
`Vol. 52, No. 5 I September—October 1998
`
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 4
`I MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 4
`
`

`

`EXCIPIENTS FOR PARENTERAL FORMULATIONS
`
`B ra in ii Name
`Administration
`Manufacturer
`Cone.
`Dosage
`Drug Name
`Excipieut
`pH when
`Slnrngg
`Route
`Form
`%\'|-UV
`Container
`applicable
`albumin (human)
`I]. I6?
`IM - inlramusctuar
`inlerfcmn aIl'a-2a, Rofaron 0-A tpuwdelj
`Roche Laboralorias
`Powder {8lcI'ilu} vial
`Iecombinanl
`
`albumin {human}
`
`albumin (human)
`
`0.1
`
`0.]
`
`IL - inlraiesional
`
`intufarnn aLl‘a-‘Eb,
`recombinant
`
`inlmn A
`
`IM - inlramuscular
`
`interferon a1fa—2b,
`recombinanl
`
`Tum:-n A {solution}
`
`albumin (human)
`
`I16
`
`IV - intravenous
`
`aniatreplase
`
`Eminase ®
`
`albumin {human}
`
`0.‘? - 0.8
`
`IV - intravenous
`
`albumin human USP
`
`l.D
`
`IV - intravenous
`
`antiliemophilic
`faciar {human}
`rFacInr VIII. .-'\|II-‘}
`algluoeraae
`injection
`
`Hlllnate-PT"
`
`Celedasuifi
`
`alcohol
`
`30.5 Lw’v%]
`
`3.0 - 4.0
`
`IV-inllavenous
`
`Eloposide
`
`VcP¢5id
`
`6.8 (wv)
`
`IV - inuavanoua
`
`10.0
`
`6.3 - I-‘.2
`
`IM -inirarnusclllar
`
`liozhymnine
`sodium injecuon
`{Till
`diguxin
`
`Triustal
`
`Lanoxin
`
`Sclleling
`Corporalion
`
`Schcring
`Corpolalion
`
`Rube:-ts
`Pharmaceutical
`
`Almoifl
`Pharmacculical
`
`Genzyme
`Corporalirm
`
`Brisrol—Myers
`Squibb-Dnculogy
`
`SmiIhK_l.1'.nn Etecham
`Pharrnaoeulicals
`
`Powder
`
`vial
`
`Solution
`
`vials
`
`Lyuphilized
`
`vial
`
`Lyophiliiwd
`
`single dose via|
`
`Soluli-an
`
`glass boulc
`
`Solulion
`
`multiple dose
`
`Solulion
`
`amber-glass Vials
`
`Glam-Welluome
`
`Solulicn
`
`ampul
`
`alcohol
`
`alcohol
`
`alcohol
`
`alcohol
`
`alcohol
`
`6.1 (VN)
`
`3.6 1 [L4
`
`[M - intramuscular
`
`dihydroergotamine DJ-LE. 45 ®
`masylate
`
`Sandal
`
`Solution
`
`arnpuls
`
`10.0
`
`IOJ3
`
`‘-9.5
`
`1M - inlI'a.m'.I.sL'.uIa.r
`
`pantobarbilal
`sodium injealion
`
`Nenlbutaisodium
`Solution
`
`Abbott Laburaloliea
`
`Soluliun
`
`ampul
`
`6.3 - 'l'.2
`
`IM - inlramuscular
`
`digoxin
`
`Lanoxin (Diguuin)
`Imitation
`
`Glaxo Welleotne
`
`Solution
`
`-1l'1'lpLi1s
`
`Solulion
`
`aleli-vials
`
`alcohol
`
`alcohol
`
`10.0
`
`I0.[)
`
`12.0
`
`IV - intravenous
`
`phanylain sodium Diianlin
`lnjeclic-fl, USP
`
`Parka-Davis
`
`IM - inl.tarnuDclIllr
`
`lceloraiac
`Irornethamine
`
`Tsaradol
`
`Synmr. Labaralories
`
`Sclulion
`
`Tubox caflridge
`
`alculml (Ph. Hair)
`
`32.9 (Viv)
`
`N - inlravenuus
`
`aloohol (USP)
`
`0.61 (WV)
`
`4.0 i 0.3
`
`IM —in'Lra1'rrus4:II]ar
`
`cyslnsporina
`uoncenlrala for
`iniaclirm USP
`oxylocin
`
`Sandirnmune ®
`
`Synlocinon ®
`
`alcohol (USP)
`
`6.] [wv%)
`
`3.6 5: 0.4
`
`IM — inlramuscular
`
`alpha
`
`aluminum
`
`1.0
`
`50.1?
`
`IM - intramuscular
`
`1.\-‘I-inlramuscular
`
`aluminum
`
`50.0001
`
`IV - intravenous
`
`aluminum
`
`$0.034
`
`-- T.-I
`
`1M-iI:1ra.muacuI.aI
`
`aluminum
`
`aluminum
`
`aluminum
`
`$0.16
`
`50. I6
`
`$0.16
`
`[M - inlramuaaular
`
`1M — inlrarnuacular
`
`IM - intra:-ru.w:u|.ar
`
`Sandoz
`Pharmaocutinals
`
`solution
`
`Amp!-I.l
`
`Sandoz
`
`Sandov.
`
`Roerig
`
`Snlulion
`
`arnpul
`
`solution
`
`arrlpuls
`
`Solution
`
`1-nullidosn: Vial
`
`dihydroergotaminc I}.H.E. 45 ® or Dyhniergo!
`rnaaylatc
`®
`iniectioll. USP
`oxytelracycline
`
`Terramycin
`
`Diphtheria and
`Telanus Toxnids
`and Acellular
`
`antihamophilic
`faclor {Human}
`
`Diphtheria at
`Tetanus Toxoidr.
`and Accllular
`combinanlion of
`refined ma nus &
`diphlheria loxoids
`refined telanus
`Ioxoid
`
`diphlheria it
`manna Ioxoids &
`Perlusais Vaccine
`
`Anei-Imune
`
`Le-lerle Laboralorjas
`
`SuspanaiDn{afi
`
`nlultidosa vial
`
`Koaic ®-HP
`
`Tripur1.ia'“‘
`
`Bayer
`Curpmation-Bintogi
`
`Lyopllilized
`
`single dose bolllt‘
`
`Connaughl
`Laboratories.
`
`inc.
`
`Soluliazdsuspc Vial
`
`Tetanus & Diphlheria
`Toxoids miambed {Adull
`
`Ludarle Laboralories
`
`Suspension
`
`Vinl
`
`Telanua Toxoicl Adscrbetl,
`a|un1iaJ.In1
`
`Lederie Lab:-raiurics
`
`suspension
`
`vial
`
`Tri-1n1mLIn-nl
`
`Lcdcrlc Labotaloiics
`
`Suspcnsioniafl multidosc vials
`
`242
`
`PDA Journal of Phannaceutical Science & Technology
`
`MYLAN PHARMS. INC..EXHIBIT 1043 PAGE 5
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 5
`
`

`

`EXCIPIENTS FOR PARENTERAL FORMULATIONS
`
`Elcipient
`Cnnc.
`pii where Adntinlstratirm
`Drug Name
`Brand Name
`Manufacturer
`Dosage
`Storage
`
`
`
`
`
`
`FormRouteapplicable“AWN Container
`
`aluminum
`0.05
`N — intramuscular
`hepatitis A vaccine Havi-ix (Hepatitis A
`Smithlilim Bnechatn
`Suspension
`sing]: dose vial
`
`
`Vaccine. lnaclivatcdl
`Biologieals
`
`aturrtinum
`1104 - 0.32
`EM — inlrarnuscutar
`combination of
`Diphtheria alt Tetanus
`SmithKJine Beecham
`Suspension
`viala
`
`
`;_
`purified lelanus 3:
`Toxoids & Pa1TLtasi.s
`Pillfm-'It‘»eIJlI'GaiS
`diphtheria
`i
`
`
`
`
`I
`
`a.[uminLim
`
`50.034
`
`IM - intramuscular
`
`combines
`diphtheria Sc
`tetanus tmtoids
`
`Diphtheria & Tetanus
`Toxoids & Pertussis
`
`Connaught
`Laboratories, inc.
`
`Turbid Liquid
`
`vial
`
`alumjnunt
`
`~l.I.0S
`
`TM - intramuscular
`
`Rcoornbivax HE
`
`Merck & Company
`
`Suspension
`
`single dose vial
`
`aluminum
`
`0.05
`
`IN! - intramuscular
`
`l-Ingcrix~B
`
`Smilitlilina Beechartl
`Pharmaceuticals
`
`Suspensiuil
`
`single dose I-isl
`
`aluminum
`
`2.0
`
`[M — intramttscular
`
`Sotganal
`
`Suspension
`
`tnultidose vial
`
`aluminum
`SCl.|6
`IM - intrarnuscujnr
`combination of
`Diphtheria Jr. Tolanux
`Lcdcrlc Laboratories
`.‘iI.t:iponaion[aft
`vial
`refined diphtheria
`Toxoids Adaorbed.
`-it tetanus tuxoids
`
`aluminum
`£0. 11"
`IM — intramuscular
`Diphtheria &
`Terran-tune. (DTP-l[l.vOC)
`Ledelle Laboratories
`Suspertr-iontafI
`vial
`Tetanus Toxoids
`
`
`and Ftrllrssis
`
`aluminum
`0.045
`IM - intrarnuscular
`haemophiius b
`Pcdt-'aJ:IIiB
`Merck & Company
`1-ltotihilizcd
`single dose Vials
`
`
`conjugate vaccine
`frrteninzocoecai
`hepatitis E
`vaccine
`{recombinant}
`lrepalilis B
`vaccine
`{recombinant}
`aurolhiogiucose
`
`
`
`
`
`Scherins
`Corporation
`
`aluminum phosphate $0.1
`IM - intramuscular
`inactivated CV5
`Rabies Vaccine Adsorhed
`Srnilhiiiinc Beccharn
`Suspension
`vial
`
`
`
`Ki5s1ing,fMDPH.
`Plrarrrtaceuliclis
`It
`rabies virus
`:
`amino acid
`0.3
`TM - intramuscular
`hepatitis A vaccine Havtix (Hepatitis A
`Stnithifiiine Beecbam
`Suspension
`single dose Vial
`
`Vaccine, Inactivalcd)
`Biological:
`
`ammonia
`0.219
`W -- intravenous
`liuihyronine
`‘i‘rior.ta1
`Smilliltiinc B;-oeham
`Solution
`amber-glass vials
`
`
`sodium injection
`Pharmaceuticals
`{T3}
`hurnetanidc
`
`amrnorruum acetate
`
`0.4
`
`-vi-‘.0
`
`IM - intramuscular
`
`Bumex it
`
`Roche Laboratories
`
`Soiulion
`
`ampuls
`
`II
`
`E
`
`5
`
`
`
`ammonium hydroxide
`SC — sub\:u1aneous
`pentagaslrin
`Peptavlon
`Wyeth-Ayers:
`Suiulion
`ampules
`
`
`
`anhydrous citric acid
`0.0l 1'5
`N v intravenous
`liothyronine
`Trioslat
`Smilliiiline Beeclaarn
`Solution
`arnber--glass vials
`
`
`sodium injection
`Pharmaceuticals
`{T31
`rligolltin
`
`
`
`arrhydrolrs citric acid
`
`0.08
`
`6.8 -
`
`'.''.2
`
`IM - intramuscular
`
`La noxin
`
`Glaxo-Wclloomc
`
`Solution
`
`arnpul
`
`
`
`anhydrous citric acid
`
`0.03
`
`6.8 - 12
`
`IM - intramuscular
`
`digoxin
`
`Lnnoarin (Diguxirn
`lniection
`
`Glaxo Wclloome
`
`Solution
`
`an-ipuls
`
`anhydrous dextrose
`
`-1.5
`
`3.0 - 4.0
`
`IV - intravenous
`
`labelaiol
`hydrochloride
`
`Trartdato Injcedun -El
`
`Glam Wclioomc
`
`Solulion
`
`vials
`
`
`arihyclrous citric acid
`3.0 - 4.0
`N v intravenous
`dacarhazine
`D‘I'IC~Dc-me Sterile
`Bayer
`Solid
`vials
`
`Corporation-Pharma
`
`
`
`anhydrous dextrose
`
`41.5
`
`3.0 - 4.0
`
`IV - intravenous
`
`labclolol HC1
`
`Ntarrnodyne
`
`Solution
`
`muitidose vial
`
`Schering
`
`
`Corporation
`
`anhydrous dextrose
`S.LI
`IM - intramuscular
`‘.'.-uprenorphine
`Huprenex
`Reckill & Colman
`Solution
`glass .-«nap-ampuls
`liydrouzhloride
`Pharmaceuticals
`
`anhydrous sodium
`
`6.0
`
`9.5 - ILD
`
`[V - inlravenous
`
`Brevitsl Sodium
`
`Eli Liily & Company
`
`Freeze-dried
`
`vials
`
`
`Methohexilal
`Sodium for
`
`
`inicctiun
`
`arginirtu
`LS6 v 26.0
`4.5 - 7.5
`{M - intramuscular
`aztreunam for
`."\ZiCllll'II for Injection
`Eiiistol-Myers
`Lyopliiiized
`vials
`
`
`irtjtclion
`Squib'b~0ncoiogy
`
`ascorbic acid
`0.043 - 0.4%
`W - intravenous
`doxycycline
`Vihramycin Irilriivertuus
`Rot-rig
`I‘ti\\'der
`vial
`
`hyciatc for
`inieetion
`
`
`
`
`Vol. 52, No. 5 I September—October 1998
`
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 6
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 6
`
`

`

`EXCIPIENTS FOR PARENTERAL FORMULATIONS
`
`Storage
`Dosage
`Manufacturer
`Brand Name
`Drug Name
`pH where Administration
`Conc.
`Exelplent
`
`
`
`
`FormRouteapplicable%Wr'\r' Container
`0. I
`IM - intramuscular
`Solution
`ascorbic acid
`imipramirre
`Tofran.i.1
`CibaGene\fa
`ampuis
`hrdrochlorirle USP
`Corporation
`
`ascorbic acid
`
`ascorbic acid
`
`ascorbic acid
`
`ascorbir. arid
`
`0.2
`
`0.2
`
`0.2
`
`I .0
`
`1M - inrramuscuiarrsoc
`
`chiorpramazine
`hydrochloride
`
`Thorazinc-atnpule
`
`Smirh1(Iine Beecham
`
`Solution
`
`ampulc
`
`1M - inLramu.9cIJl.ar (soc
`
`chlorpromazine
`hydrochloride
`
`Thorazine
`
`Srrtirhliiing Boeoltirn
`
`Solution
`
`multicloae r-gar,
`
`3.4 - 4.5
`
`various
`
`SC - wbcuunwus
`
`Marcaine Hydrochloride
`bupivacaine
`hydrochloride and with Epinephrine
`enlneohrinc
`Epincph:-ins
`
`Sus—p1'rtin.e IE
`
`Sanofr Winthrop
`
`Solution
`
`single dose vials
`
`Forest
`Pirnnmceuricala Inc.
`
`Suspension
`
`ampui
`
`ascorbic acid USP
`
`0. 1
`
`[M - intramuscular
`
`ihielhyiperazine
`malate USP
`
`Torecan ®
`
`Roxarrc
`Lahoratoriesr Inc.
`
`Solution
`
`arrtpui
`
`Iaparagine
`
`[VS - iurravesicai
`
`an attenuated live
`culnire preparation
`of BCG vaccine
`
`‘1‘{Cl':'.®BCG
`
`Organon
`
`Freeze-dried
`
`ampules
`
`benzaikonium
`
`0.02
`
`5.8 — 12
`
`ID - inlradcnnal.
`
`benzanosulrcnic acid
`
`3.25 — 3.65
`
`[V — intravenous
`
`Celcstone Soiuapan
`balamclhaaonc
`sodium phosphate Suspension
`Jr. belamelhaaorre
`arracuriurn besylate Tracriurn
`
`Schcring
`Corporation
`
`Suspension
`
`Wrulridose vial
`
`Glaxo Welloorue
`
`Solution
`
`single use vial
`
`benzethonium
`
`0.0 - 0.0i‘
`
`5.0 - 6.0
`
`EM - intramuscular
`
`diphenhydraminc
`hydrochloride
`
`Bcnadryl
`
`I'aI'lro Darn‘:
`
`Solution
`
`arnpuiea
`
`I:-enzerlroniurn
`
`0.0 —
`
`it til
`
`EM - intramuscular
`
`burorpiranoi
`Iarlrare
`
`Sradnl ® Injection
`
`Aporhccon!I3rs'srol-
`Myers Squibb
`
`Solution
`
`vial
`
`benzyl alcohol
`
`benzyl alcohol
`
`3.0
`
`0.9
`
`3.0 - 4.0
`
`!\-“iniratrenous
`
`Elopoaide
`
`VePeairl
`
`5.0 - 7.5
`
`EM-intramuscular
`
`Dalalonc DJ‘. 09
`
`Bristol-Mtycrs
`Squibb-Oncology
`
`Forest
`Pharmaceuticals
`
`Solution
`
`multiple dose
`
`Suspension
`
`vials
`
`Suspension
`
`vials
`
`5.0 - ‘LU
`
`IM-intramuscular
`
`Doirarnelhaaonc
`Acetate
`Suspension
`Conisone Aceialc
`
`Cc-none Acclale
`
`Merci:
`
`uh. Company
`
`5.0 — 7.5
`
`IM-intramuscular
`
`dexamerhasone
`acetate
`
`Decadmnvi...-\
`
`Merck & Company
`
`Suspension
`
`vials
`
`6.0 - 3.0
`
`JAR — inlraarlicular
`
`Prconiaolonc
`Tcbulale
`
`Hy-dracortisonc
`acetate
`
`Hydallra T. E. A.
`
`Merck & Company
`
`Suspension
`
`vials
`
`i-iydrocnnono Acetate
`
`Merck Jr Company
`
`Suspension
`
`vials
`
`benzyl alcohol
`
`benzyi alcohol
`
`benzyl alcohol
`
`0.9
`
`0.9
`
`0 9
`
`benzyl alcrrhoi
`
`0.9
`
`5.0 - ?.0
`
`IAR.
`
`- inrraanieular
`
`henzyl alcohol
`
`0.89-0.93
`
`3.5 -
`
`‘.|'.0
`
`L'\-i - intramuscular
`
`Merhylpredniaalo Dcpo—Medro1
`no acetate
`
`The Upjohn
`Company
`
`Suspension
`
`single dose viai
`
`bonzyl alcohol
`
`0.90
`
`benzyl alcohol
`
`0.90
`
`-6.0
`
`~6.0
`
`IM - inlramuacular
`
`trilmcirrolorre
`diacelale
`
`Mialocorl Fan: (P)
`
`Frrjisawa
`
`Micronixed
`
`vial
`
`IL - intralesionai
`
`triamciooione
`diacelatc
`
`M-iarocarr
`
`Fujiaawa USA, Inc.
`
`Micronined
`
`vial
`
`benzyl alcohol
`
`0.90
`
`4.3 . o.S
`
`IL - inlrrllcsional
`
`benzyi alcohol
`
`2.02
`
`IV - intravenous
`
`Iriamcinolonc
`hexacelonide
`5|:-Emnaion
`uniodarone l-I.c|
`
`Arisroapan Suspension 5
`m.r:r'rr1l
`
`Fujisawa USA. Inc.
`
`Suspension
`
`viai
`
`Cordarolre Intravenous
`t‘I.'.‘ord.IrDne IV’!
`
`Wyeth-Ayersl
`
`Solution
`
`ampuls
`
`benzyl alcohol
`
`benzyl alcohol
`
`0.9
`
`1.0
`
`N — intravenous
`
`Enalaprilar
`
`Vasotec I.V.
`
`Merck & Company
`
`Solution
`
`vial
`
`-'3 .0
`
`IV - intravenous
`
`rrridazolarrr
`l1)td.rochIorid.e
`
`Verses!
`
`I-[olTman - ]'...trRochc
`inc.
`
`Solution
`
`vials
`
`244
`
`PDA Journal of Pharmaceutical Science 8. Technology
`
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 7
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 7
`
`

`

`
`
`
`Exclpient
`
`benzyl alcohol
`
`henzyl alcohol
`
`bcnzyl alcohol
`
`benzyl alcohol
`
`bunzyt alcohol
`
`EXCIPIENTS FOR PARENTERAL FORMULATIONS
`
`Cone.
`%W.t\r'
`
`pl! where Administration
`Drug Name
`Brand Name
`Manufacturer
`Dosage
`Storage
`
`applicable
`Rome
`Form
`Container
`
`0.5‘
`
`0.5
`
`1.0
`
`0.9
`
`1.2
`
`1M - intramuscular
`
`hydroxyzine
`h)-drochloridc
`
`Vjsraril
`
`Rocrig
`
`Solulion
`
`muliidoaa vials
`
`5.8 - 6.5
`
`JIM - inlramuacular
`
`gold sodium
`thiomalate
`
`My-ochrysine
`
`Merck & Cur-rrpany
`
`Solution
`
`ampuls
`
`3.5 - 6.0
`
`IM - inlramuaoulal
`
`nelilmtcin sulfate. Netromycin Injection
`USP
`
`Sizhcrlng Bioehem.
`Corporation
`
`Solution
`
`vials
`
`3.9 - 5.0
`
`IV - intravenous
`
`IM - intramuscular
`
`doxacurium
`chloride
`
`haloperidol
`dccanualu
`
`Nunomax
`
`Glaxo Wcllcon-in
`
`Solution
`
`n1IJ.ltidoac Vial
`
`Haldol Dacanoale S0 and
`100
`
`McNeil
`Pharmaceutical
`
`Solution (in
`
`ampuls
`
`IV — inlravenous
`
`tcniposid:
`
`Solution
`
`ampules
`
`hcnzyl atoohol
`
`benzyl alcohol
`
`benzyl alcohol
`
`benzyl alcohol
`
`beuzyl alcohol
`
`3.0
`
`1.0
`
`1.0
`
`0.5‘
`
`1.5
`
`-5.0
`
`Vumon Injcclion
`Concentrate {VM-1'6)
`
`Bristol-Myers
`Squibb-Oncology
`
`~£0.0
`
`IV’ - inlravonuus
`
`trimelhoprim and
`sulfamelhoxazoie
`
`Seplta I.\«". Infusion
`
`Glaxo Welloome
`
`Solulion
`
`rnullidose vials
`
`IM - intramuscular
`
`lorazopam
`
`Alivaii
`
`Wyolh-Ayerall
`
`Solution
`
`sterile cartridge
`
`“L5
`
`~10
`
`IM - inuamuacuiar
`
`IM — inlramuscular
`
`melholrinreprazine Lovoprome
`as ill!
`lwdmchloride sail
`chlordiazepoxidc
`hydmchloride
`
`Librium injcclablc {IM}
`
`lmmunex
`Corp-oralion
`
`Solution
`
`vials
`
`Roche Products. Inc.
`
`Crystalline
`
`amber ampulc
`
`henzyl alcohol
`
`0,945
`
`IM - intramuscular
`
`Iineomyain
`hydrochloride
`
`Lincocirt atcrilo solution
`
`The Upjohn
`Company
`
`Solution
`
`vials
`
`SC - subculaneous
`
`ieuprolide acetate
`
`Lupmn Injection
`
`Solution
`
`multidoae vial
`
`benzyl alcohol
`
`0.9
`
`benzjrl alcohol
`
`0.5-t
`
`ICN - inlraoavornoaal
`
`atprustadi!
`
`Cavelject Sterile Powder
`
`benzyl alcohol
`
`bonzyl alcohol
`
`bcnzyl alcohol
`
`0.‘)
`
`2.0
`
`I .0
`
`-6.8
`
`W - intravenous
`
`aminocaproic acid Amicar Injection, USP
`
`[M - intramuscular
`
`physosligminc
`salicylatt
`
`Anlilirium
`
`TAP
`Phannaoaulicals,
`
`"Hue Upjohn
`Company
`
`lmmunex
`Corporation
`
`Foreal
`
`Freeze-dried
`
`vial
`
`Solution
`
`vial
`
`Solulion
`
`ampuls
`
`-7.0
`
`IM - intramuscular
`
`bumclanide
`
`Bumexlfi
`
`Roche Labomories
`
`Solution
`
`ampuls
`
`honzyl alcohol
`
`0.945
`
`N v inlmmuaoular
`
`clindamycin
`phosphate
`
`Clrocin Phosphate Smile The Upjohn
`Solution
`Company
`
`Solution
`
`vials
`
`bcrtzyl alcohol
`
`l.S
`
`IM — intramuscular
`
`diazepam
`
`Valium lnjectable
`
`Roche Products
`
`Solution
`
`ampuls
`
`benzjrl alcohol
`
`2.0
`
`benzyl alcohol
`
`0. 35
`
`bcnzyl alcohol
`
`benzyt alcohol
`
`benzyl alcohol
`
`banzyi alcohol
`
`1.0
`
`L2
`
`1.5
`
`0.‘)
`
`1M - inlramuscularlsnc
`
`chiorpromazinc
`hydrochloride
`
`Tliorazinv:
`
`5rnitlIKlino Bveocham
`
`Solution
`
`multidose vials
`
`[M - intramuscular
`
`prochlorporazino
`I5 I11: ediaylalc
`
`Cornpazine
`
`Sm.i'Ih[CJi.ne Boecharn
`Pharrnaoeuticals
`
`Solution
`
`vials
`
`6.1 3: 0.3
`
`N - inlravenoua
`
`IM - inll1I'.|1|lSE.LIlll
`
`1301 -intramuscular
`
`5.0 — 10
`
`[M - :'n|.ranu:scuIar
`
`epoetin alfa
`{recombinant
`human
`fluphenazine
`Iiecarvoatc
`iniection
`fluphenazine
`Enanthale
`Iniecliori
`phytonadione
`(vilamin 1(1)
`
`I.-Ipogen ® - multidoae
`
`Amgert, Lric.
`
`Solution
`
`mullidose vial
`
`Prolixin Decanmle
`
`Prolixin Erianlhate
`
`ApoIhecon:'lJrisIol-
`Myers Squibb
`
`Apothecon.fBriatol-
`Myers Squibb
`
`Solution
`
`single dose
`
`Solution
`
`vials
`
`J\qua.'V|c-phyton
`
`Merck & Company
`
`Aqumu
`
`rlmpuls
`
`Vol. 52, No. 5 I Septamber—October 1993
`
`245
`
`
`MYLAN PHARMS. INC. EXHIBIT 1043 PAGE 8
`
`

`

`EXCIPIENTS FOR PARENTERAL FORMULATIONS
`
`Dosage
`Manufacturer
`Brand Name
`Drug Name
`pH where Adtninislrattinn
`Cone.
`Exclpient
`Storage
`Container
`
`
`
`Routeapplicable%\’-“IV Farm
`rnullidosc vials
`0.9
`TM - intramuscular
`benzyl alcohol
`chorionic
`Pregnyl -39
`Orgarlon
`Powder
`gonadolropin for
`infection. USP
`rnetholrcxate
`sodium
`
`Solution
`
`vial.
`
`benzyl alcohol
`
`0.9
`
`-3.5
`
`IA - inlraarlerial
`
`Melholrexale Sodium
`[nieclion
`
`l.i-nmurmr
`Corporation
`
`hertz)?! alcohol
`
`henzyl alcohol
`
`I.D
`
`1.0
`
`-i0.0
`
`IV - intravenous
`
`-40.0
`
`IV - inlravenous
`
`lrimelhoprimand
`suifarrlelhoxazolc
`
`Irimelhoprim and
`suifarnclhoxazolc
`
`Seplra IV Infusion
`
`Glaxo Wollcorne
`
`Soluliort
`
`Svc