Handbook of
`.PHARMACEUTICAL
`EXCIPIENTS
`
`Second Edition
`
`Edited by
`Ainley Wade and Paul J Weller
`
`I b" EXHIBIT
`I ~2,b i,.
`
`I
`......
`
`American Pharmaceutical. Association
`Washington
`
`1994
`
`The Pharmaceutical Press
`London
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`© Copyright 1986, 1994 by the American Pharmaceutical Association, 2215 Constitution Avenue NW, Washington,
`DC 20037-2985, USA, and The Pharmaceutical Press, Royal Pharmaceutical Society of Great Britain, 1 Lambeth High
`Street, London, SEl 7JN, England.
`
`A catalogue record for this book is available from the British Library.
`
`Library of Congress Catalog Card Number: 94-79492.
`
`International Standard Book Number (ISBN) in the UK: 0 85369 305 6
`International Standard Book Number tISBN) in the USA: 0 91730 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, with011t prior written permission from
`the joint publishers.
`
`Typeset in Great Britain by Alden Multimedia, Northampton.
`Printed and bound in Great Britain by
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`552 Carnauba Wax
`
`Carnauba Wax
`
`1. Nonproprietary Names
`BP: Carnauba wax
`PhEur: Cera catnauba
`USPNF: Carnauba wax
`
`2. Synonyms
`903; brazil wax; carnnda wax.
`
`3. Chemical Name and CAS Registry Number
`Carnauba wax [8015-86-9]
`
`4. Empirical Formula Molecular Weight
`Carnauba wax consists primarily of a complex mixture of
`esters of acids and hydrnxyacids. Also present are acids,
`oxypolyhydric alcohols, hydrocarbons, .resinous matter and
`water.
`
`5. Structural Formula
`See Secti.on 4.
`
`6. Functional Category
`Coating agent.
`
`7. Applications in Pharmaceutical Formulation or
`Technology
`Carnauba wax is widely used in cosmetics, certain foods and
`pharmaceutical formulations.
`Carnauba wax is the hardest and highest melting of the waxes
`commonly used in pharmaceutical formulations and is used
`primarily as a 10% w/v aqueous emulsion to polish sugar(cid:173)
`coated tablets. Aqueous emulsions may be prepared by mixing
`carna,1ba wax with an ethanolamine compound and oleic acid.
`The carnauba wax coating produces tablets of good luster
`without rubbing. Carnauba wax may also be used in powder
`form to polish sugar-coated tablets.
`Carnauba wax (10-50% w/w) has also been used alone or with
`stearyl alcohol to produce sustained release solid dosage
`formulations.< 1-4>
`
`8. Description
`Carnauba wax occurs as a light brown to pale yellow colored
`powder, flakes, or irregular lumps of a hard, brittle wax. It
`possesses a characteristic bland odor and practically no taste.
`It is free from rancidity. Commercially, various types and
`grades are available.
`
`9. Pharmacopeial Specifications
`
`Test
`
`Identification
`Appearance of solution
`Melting range
`Residue on ignition
`Total ash
`Heavy metals
`Acid value
`Saponification value
`
`PhEur 1989
`+
`+
`80-88°C
`
`,;;; 0.25%
`
`2-7
`78-95
`
`USPNF XVII
`
`8l-86°C
`,;;; 0.25%
`
`,;;; 0.004%
`2-7
`78°95
`
`10. Typical Properties
`Flash point: 270-330°C
`90 = 1.450
`Refi·active index: n 0
`Solubility: soluble in warm chlorofom1, and warm toluene;
`slightly soluble in boiling ethanol (95%); practically insoluble
`in water.
`Spec(fic gravit_y: 0.990-0.999 at 25°C
`Unsaponijied matter: 50-55%
`
`11. Stability and Storage ~onditions
`Carnauba wax is stable and should be stored .in·a well-closed
`container, in a cool, dry, place.
`
`12. Incompatibilities
`
`13. Method of Manufacture
`Carnauba wax is obtained from the leaf buds and leaves of
`Copernicia cerifera Mart. (Fam. Palmae}. The leaves are dried
`and shredded and the wax the11 removed by the addition of hot
`water.
`
`14. Safety
`Camauba wax is widely used in oral pharmaceutical fonnula(cid:173)
`tions, cosmetics, and certain food products and is generally
`regarded as an essentially nontoxic and nonirritant material.
`
`15. Handling Precautions
`Observe normal precautions appropriate to the circumstances
`and quantity of material handled.
`
`16. Regulatory Status
`GRAS listed. Accepted for use in certain foods in the UK.
`Included in the FDA Inactive Ingredients Guide (oral capsules
`and tablets, also topical preparations). Included in nonpar(cid:173)
`enteral medicines licensed in the UK.
`
`17. Pharmacopeias
`Br, Eur, Fr, Ger, Jpn, Neth, Swiss and USPNF.
`
`18. Related Substances
`
`19. Comments
`In cosmetics, carnauba wax is mainly used to increase the
`stiffness of formulations., e.g. lipsticks and mascaras.
`
`20. Specific References
`I. Wiseman EH, Federici NJ. Development of a sustained-release
`aspirin tablet. J Pharm Sci 1968; 51: 1535-1539.
`2. Prasad CM, Srivastava GP. Study of some sustained release
`granulations of aspirin. Indian J Hosp Pharm 1971; 8: 21-28.
`3. Dave SC, Chakrabarti T, Srivastava GP. Sustained release tablet
`formulation of diphenhydramine hydrochloride (Benadryl) • part
`II. Indian J Pharm 1974; 36: 94-96.
`4. Kumar K, Chakrabarti T, Srivastava GP. Sustained release tablet
`formulation of diethylcarbamazine citrate (Hetrazan). Indian J
`Pharm 1975; 37: 57-59.
`
`21. General References
`Briquct F, Brossard C, Ser J., Duchene D. Optimization of a sustained
`release formulation containing spherical microgranules produced
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`by extrusion-spheronizalion [in French]. STP Pharma 1986; 2: 986-
`994.
`
`22. Authors
`USA: NH Kobayashi.
`
`Carnauha Wax 553
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`558 White Wax
`
`White Wax
`
`1. Nonproprietary Names
`BP: White beeswax
`PhEur: Cera alba
`USPNF: White wax
`
`2. Synonyms
`Bleached wax; E901.
`
`3. Chemical Name and CAS Registry Number
`White beeswax [8012-89-3]
`
`4. Empirical Formula Molecular Weight
`White wax is the chemically bleached form of natural beeswax,
`see Section 13.
`Beeswax consists of 70-75% of a mixture of various esters of
`straight chain monohydric alcohols with even number carbon
`chains from C24-C36 esterified with straight chain acids which
`also have even numbers of carbon atoms up to C36 together
`with some <:\~ hydroxy acids. The chief ester is myricyl
`palmitate. Also present are free acids (about 14%) and
`carbohydrates (about 12%) as well as approximately 1 % free
`wax alcohols and stearic esters of fatty acids.
`
`5. Structural Formula
`See Section 4.
`
`6. Functional Category
`Emulsion stabilizer; stiffening agent.
`
`7. Applications in Pharmaceutical Formulation or
`Technology
`White wax is a chemically bleached form of yellow wax and is
`used in similar applications, such as to increase the consistency
`of creams and ointments, and to stabilize water-in-oil
`emulsions. White wax is also used to polish sugar-coated
`tablets and to adjust the melting point of suppositories.
`See also Yellow Wax.
`
`8. Description
`White wax consists of tasteless, white or slightly yellow(cid:173)
`colored sheets or fine granules with some translucence. Odor is
`similar to yellow wax although it is less intense.
`
`9. Pharmacopeial Specifications
`
`Test
`
`PhEur 1981
`
`USPNF XVII
`
`Melting range
`Saponification cloud test
`Saponification value
`Fats, or fatty acids, Japan wax,
`rosin and soap
`Acid value
`Ester value
`Ratio number
`Ceresin, paraffin and
`certain other waxes
`Glycerin and other polyhydric
`alcohols
`
`6J-65°C
`
`87-104
`
`17-24
`70-80
`3.3-4.3
`+
`
`~. 0.5%
`
`62-65°C
`+
`
`+
`
`17024
`72-79
`
`10. Typical Properties
`Arsenic: ,,; 3 ppm
`Density; 0.95-0.96 g/cm3
`Flash point: 245-258°C
`Heavy metals: ,,; 0.004%
`Iodine number: 8- l l
`Lead: ,.;; 10 ppm
`Melting point: 61-65°C
`Peroxide value: ,,; 8
`Solubility: soluble in chloroform, ether, fixed oils, volatile oils
`and warm carbon disulfide; sparingly soluble in ethanol (95%);
`practically insoluble in water.
`Unsaponified matter: 52-55%
`
`HPE Laboratory Project Data
`
`Method
`
`Lab#
`
`Density
`
`DE-I
`
`7
`
`Results
`0.958 ± 0.006 g/cm3
`
`IL Stability and Storage Conditions
`When heated above 150°C esterification occurs with a
`consequent lowering of acid value and elevation of melting
`point. White wax is stable when stored in a well-closed
`container; protected from light.
`
`12. Incompatibilities
`Incompatible with oxidizing agents.
`
`13. Method of Manufacture
`Beeswax (yellow wax) is obtained from the honeycomb of the
`bee [Apis mellifera Linne (Fam. Apidae)], see Yellow Wax.
`Subsequent treatment with oxidizing agents bleaches the wax
`to yield white wax.
`
`14. Safety
`Used in both topical and oral formulations, white wax is
`generally regarded as being an essentially nontoxic and
`nonirritant material. However, although rare, hypersensitivity
`reactions to beeswax; attributed to contaminants in the wax,
`have been reported.ci.z)
`
`15. Handling Precautions
`Observe normal precautions appropriate to the circumstances
`and quantity of material handled.
`
`16. Regulatory Status
`GRAS listed. Accepted as a food additive in Europe. Included
`in the FDA Inactive Ingredients Guide (oral capsules and
`tablets, rectal, topical and vaginal preparations). Included in
`nonparenteral medicines licensed in the UK.
`
`17. Pharmacopeias
`Aust, Belg, Br, Cz, Egypt, Eur, Fr, Ger, Gr, Hung, Ind, It,
`Jpn, Mex, Neth, Nord, Port, Rom, Swiss, USPNF and Yug.
`Also in BP Vet.
`
`18. Related Substances
`Yellow Wax.
`
`19. Comments
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`20. Specific References
`1. Cronin E. Contactdennatitis from cosmetics. J Soc Cosmet Chem
`1967; 18: 68)-691.
`2. Rothenborg HW. Occupational dermatitis in beekeeper due to
`poplar resins in beeswax. Arch Dermatol 1967; 95: 381-384.
`
`21. General References
`Puleo SL. Beeswax. Cosmet Toilet 1987; 102(6): 57-58.
`
`22. Authors
`USA: LO Bighley.
`
`White Wax 559
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`560 Yellow Wax
`
`Yellow Wax
`
`1. Nonproprietary Names
`BP: Yellow beeswax
`PhEur: Cera 11ava
`USPNF: Yellow wax
`
`2. Synonyms
`E901; refined wax.
`
`3. Chemical Name and CAS Registry Number
`Yellow beeswax [8012-89-3]
`
`4. Empirical Formula Molecular Weight
`Yellow wax is naturally obtained beeswax, see Section 13.
`Beeswax consists of 70-75% of a mixture of various esters of
`straight chain monohydric alcohols with even number carbon
`chains from C24•C36 esterified with straight chain acids which
`al~o have even numbers of c~rbon atoms up to C36 together
`with. some C 1a hydroxy acids. The chief ester is myricyl
`palm1tate. Also present are free acids (about 14%) and
`carbohydrates (about 12%) as well as approximately 1 % free
`wax alcohols and stearic esters of fatty acids.
`
`5. Structural Formula
`See Section 4.
`
`6. Functional Category
`Emulsion stabilizer; stiffening agent.
`
`7. Applications in Pharmaceutical Formulation or
`Technology
`Yellow wax is used in food, cosmetics and confectionery
`products. However, its main use is in topical pharmaceutical
`formulations, where it .is used at a concentration of 5-20% as a
`stiffening agent in ointments and creams. Yellow wax is' also
`employed in emulsions since it enables water to be incorpo(cid:173)
`rated into water-in~oil emulsions.
`In some oral formulations, yellow wax is used as a polishing
`agent for sugar-coated tablets; it is also used in sustained
`release formulations.
`Yellow wax forms a soap with borax.
`
`8. Description
`Yellow or light brown pieces or plates with a line-grained
`matt, noncrystalline fracture and a faint characteristic odor.
`The wax becomes soft and pliable when warmed.
`
`9. Pharmacopeial Specifications
`
`Test
`
`PhEur 1981
`
`USPNFXVU
`
`Melting range
`Saponitication cloud test
`Saponificatiou value
`Fats, or fatty ac.ids, Japan wax,
`rosin and soap
`Acid value
`Ester value
`
`61-65"C
`
`87-102
`
`17-22
`70-80
`
`62-65°C
`+
`c-
`+
`
`17-24
`72-79
`
`Continued
`Test
`Ratio number
`Ceresin, paraffin and
`certain other Waxes
`Glycerin and other polyhydric
`alcohols
`
`PhEur 1981
`
`USPNF XVII
`
`3.3-4.3
`+
`
`~ 0.5%
`
`10. Typical Properties
`Acid value: 20
`Arsenic: ~ 3 ppm
`Density: 0.950-0.960 g/cm3
`Flash point: 245~258°C
`Heavy metals: ~ 0.004%
`Iodine number: 8-11
`Lead: ~. JO ppm
`Melting point: 61-65°C
`Peroxide value: ,.; 8
`Refractive index: 1.440-1.445
`Solubility: soluble-in chloroform, ether, fixed oils, volatile oils,
`and ~arm c_arbon disulfide; sparingly soluble in ethanol (95%);
`pract1cally msoluble in water.
`Unsaponifled matter: 52-55%
`Viscosity (kine111atic):
`1470 mm2/s (1470 cSt) at 99°C
`
`11. Stability and Storage Conditions
`When heated above 150°C esterification occurs with a
`c01_1sequent lowering of acid value and elevation of melting
`pomt. Yellow wax is stable when stored in a well-closed
`container, protected from light.
`
`12. Incompatibilities
`Incompatible with oxidizing agents.
`
`13. Method of Manufacture
`Yellow wax isa natural secretion of bees [Apis mell(fera Linne
`(Fam. Apidae)] and is obtained commercially from honey(cid:173)
`combs. Honey is abstracted from combs either by draining or
`centrifogation and water added to the remaining wax to
`remove soluble impurities. Hot water is then added to form a
`floating melt which is strained to remove foreign matter. The
`wax is then poured into flat dishes or molds to cool and
`harden.
`
`14. Safety
`Used i~ both topical and oral formulations, yellow wax is
`generally regarded as being an essentially nontoxic and
`nonirritant material. However, hypersensitivity reactions
`attributed to contaminants in the wax, although rare, have
`been reported_(I,2J
`
`15. }Jandling Precautions
`Observe normal precautions appropriate to the circumstances
`and quantity of material handled.
`
`16. Regulatory Status
`GRAS listed. Accepted as a food additive .in Europe. Included
`in the FDA Inactive Ingredients Guide (oral capsules and
`tablets, and topical preparations). Included in nonparenteral
`medicines licensed in the UK.
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`17. Pharmacopeias
`Aust, Belg, Br, Chin, Egypt, Eur, Fr, Ger, Ind, It, Jpn, Neth,
`Nord., Port, Rom, Swiss, USPNF and Yug.
`
`18. Related Substances
`White Wax,
`
`19. Comments
`
`Yellow Wax 561
`
`20. Specific References
`I. Cronin E. Contact dermatitis from cosmetics. J Soc Cosmet Chem
`1967; 18: 681-691.
`2. Rothenborg HW. Occupational dermatitis in beekeeper due to
`poplar resins in beeswax. Arch Detmatol 1967; 95: 381-384.
`
`21. General References
`Puleo SL. Beeswax. Cosmet Toilet I 987; 102(6): 57-58.
`
`22. Authors
`USA: LD Bighley .
`
`l.
`
`•
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`SEM: 1
`Excipient: Stearic acid, 95% (Emersol /53)
`Manufacturer: Emery Industries
`Lot No.: 18895
`Magnification: 120x
`Voltage: 10 kV
`
`SEM: 2
`Excipicnt: Slearic acid, food grade (£mer.ml 63-12)
`Manufacturer: Emery fndustries
`Lot No.: 18895
`Magnilication: 120x
`Voltage: IOkV
`
`494 Stearic Acid
`
`Stearic Acid
`
`1. Nonproprietary Names
`BP: Stearic acid
`USPNF: Stearic acid
`
`2. Synonyms
`570; Crodacid; Crosterene; Glycon S-90; Hystre11e; J11dustre11e;
`Kortacid 1895; Pristerene.
`
`3. Chemical Name and CAS Registry Number
`Octadecanoic acid [57-11-4]
`
`4 . . Empirical Formula Molecular Weight
`284.47 (for pure material)
`C 18H 3602
`The BP 1993 and the USPNF XVII describe stearic acid as a
`mixture of stearic acid (C 18H 36O 2) artd palmitic acid
`(C 16H 32O2J The content of stearic acid is not less than
`40.0% and the sum of the two acids is not less than 90.0%. The
`USPNF XVII also contains a monograph for purified stearic
`acid, see Section l 8.
`
`5. Structural Formula
`CHJ(CH2) 16COOH
`
`6. Functional Category
`Emulsifying agent; solubilizing agent; tablet and capsule
`lubricant.
`
`7. Applications in Pharmaceutical Formulation or
`Technology
`Stearic acid is widely used in oral and topical pharmaceutical
`formulations. It is main!~ used iu oral formulations as a tablet
`and capsule lubricant(]-_ l although it may also be used as a
`binder,<4) or in combination with shellac as a tablet coating.
`In topical formulations, stearic acid is used as an emulsifying
`and solubilizing agent. When partially neutralized with alkalis
`or triethanolamine, stearic acid is used in the preparation of
`
`creams.<5·6) The partially neutralized stearic acid forms a
`creamy base when mixed with 5-15 times its own \veight of
`aqueous liquid, the appearance and plasticity of the cream
`being detennined by the proportion of alkali used.
`Stearic acid is also widely used in cosmetics and food products.
`
`Use
`
`Concentration(%)
`
`Ointments and creams
`Tablet lubricant
`
`l-20
`1-3
`
`8. Description
`Stearic acid is a hard, white or faintly yellow colored,
`somewhat glossy, crystalline solid or a white, or yellowish
`white, powder. It has a slight odor and taste suggesting tallow.
`See also Section 13.
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`SEM: 3
`Excipient: Slearic acid USP (Hydro.fol Acid 165?)
`Manufacturer: Shercx Chemica·1 Company Inc
`Lot No .: 9303-M639-521
`Magnification: 120x
`Voltage: .IOkV
`
`SEM:4
`Excipienl: StcaJjc acid (Hydro.fol Acid 1870)
`Manufacturer: Shcrex Chemical Company Inc
`Lot No.: 9227-M635-421
`Magnification: l20x
`Voltage: !OkV
`
`Stearic Acid 495
`
`9. Pharmacopeial Specifications
`
`Test
`
`IdentJfii:a tion
`Congealing temrerature
`Residue on ignition
`Sulfated ash
`Heavy metals
`Mineral acid
`Neutral fat or paraffin
`Acid value
`fodine value
`Organic volatile
`impurities
`Assay of ste:1ric acid
`Assay of both acids
`
`BP 1993
`
`+
`·~ 54°C
`
`.,;;; 0.1%
`.,;;; 20 ppm
`+
`
`200-212
`.,;;; 4.0
`
`USPNFXVU
`(Suppl 6)
`+
`~ 54'C
`,;;; 0.1%
`
`.,;;; 0.001%
`+
`+
`
`,;;; 4.0
`+
`
`~ 40.0%
`~ 90.0%
`
`~ 40.0%
`~ 90.0%
`
`10. Typical Properties
`Acid 11al11e: 200-212
`Density (bulk): :=::l 0.8 g/cm3
`Melting point: ~ 54°C
`Moisture content: contains practically no water.
`Sapon(fication value: 200-220
`Solubility: freely soluble in benzene, carbon tetrachloride,
`chloroform and ether; soluble in ethanol, hexane and
`propylene glycol; practically inso.luble in water.
`See also Section 18.
`
`ll. Stability and Storage Conditions
`Stearic acid is a stable material; an antioxidant may also be
`added to it, see Section 13. The bulk material should be stored
`in a well-closed container in a cool, dry, place.
`
`12. Incompatibilities
`Stearic acid is incompatible with most metal hydroxides and
`may be incompatible with oxidizing agents.
`Insoluble stearates are formed with many metals; ointment
`bases made with stearic acid may show evidence of drying out
`or lumpiness due to such a reaction when compounded with
`Zinc or calcium salts.
`A number of differential scanning calorimetry studies have
`investigated the compatibility of stearic acid with drugs
`although such laboratory studies that have suggested incom(cid:173)
`patibilities, e.g. naproxen,(7) may not necessarily be applicnble
`to formulated products.
`Stearic acid has been reported to cause pitting in the film(cid:173)
`coating of tablets coated using an aqueous film-coating
`technique; the pitting was found to be a function of the
`melting point of the stearic acid.(s)
`
`13. Method of Manufacture
`Stearic acid is manufacttired by hydrolysis of fat by continuous
`exposure to a counter-current stream of high-temperature
`water and fat in a high,pressL1re chamber. The resultant
`mixture is purified by vacuum steam distillation and the
`distillates then separated using selective solvents.
`Stearic acid may also be manufactured by hydrogenation of
`cottonseed and other vegetable oils; by the hydrogenation and
`subsequent saponification of olein followed by recrystalliza(cid:173)
`tion from alcohol; and from edible fats and oils. by boiling with
`sodium hydroxide, separating any glycerin and decomposing
`the resulting soap with sulfuric or hydroch.lor.ic acid. The
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`496 Stearic Acid
`
`Table I: Specifications of different stearic acid grades (Witco Corporation).
`
`Product
`
`Hystrene 5016
`Hystre11e 7018
`Hyslrene 9718
`J11d11stre11e 7018
`lnd11s1re11e 8718
`
`Stearic acid
`content(%)
`
`44
`68.5
`90
`65
`87
`
`Titer
`(°C)
`
`54.5-56.5
`61.0-62.5
`66.5-68.0
`58-62
`64.5-67.5
`
`Acid v11lue
`
`Iodine value
`
`Snponification
`rnluc
`
`Unsnponifiable
`mutter(%)
`
`206-210
`200-205
`196-201
`200-207
`196-201
`
`,:;; 0.5
`,:;; 0.5
`,:;; 0.8
`,:;; 1.5
`,:;; 2.0
`
`206-211
`200-206
`196-202
`200-208
`196-202
`
`,:;; 0.2
`,:;; 0.2
`,:;; 0.3
`,:;; 0.5
`,:;; 1.5
`
`stearic acid is then subsequently separated from any oleic acid
`by cold expression.
`Stearic acid is derived from edible fat sources unless it is
`intended for external use, in which case noned:ible fat sources
`may be used. Stearic acid may contain a suitable antioxidant
`such as 0.005% w/w butylatcd hydroxytoluene.
`
`14. Safety
`Stearic acid is widely used in oral and topical pharmaceutical
`fonnulations; it is also used in cosmetics and food products.
`Stearic acid is generally regarded as a nontoxic and nonirritant
`material. However, consumption of excessive amounts may be
`liarmful.
`LDso (mouse, IV): 23 mg/kg(9)
`LD50 (rabbit, skin): > 5 g/kg
`LDso (rat, IV): 21.5 mg/kg
`
`15. Handling Precautions
`Observe normal precautions appropriate to the circumstances
`and quantity of material handled. Stearic add dust may be
`irritant to the skin, eyes and m,ucous membranes. Eye
`protection, gloves and a dust respirator are recommended.
`Stearic acid is combustible.
`
`16. Regulatory Status
`GRAS listed. Accepted as a food additive in the UK. Included
`in the FDA Inactive Ingredients Guide (buccal tablets, oral
`capsules, solutions, suspensions and tablets, topical and
`vaginal preparations). Included in nonparenteral medicines
`licensed in the UK.
`
`17. Pharmacopeias
`Aust, Belg, Br, Braz, Chin, Cz, Egypt, Fr, Hung_, Ind, It, Jpn,
`Mex, Nord, Rom, Swiss, USPNF and Yug.
`
`18. Related Substances
`Calcium Stearate; Magnesium Stearate; palmitic acid; purified
`stearic acid; Zinc Stearate.
`Palmitic acid: C 16H 3202
`Molecular weigh/: 256.42
`CAS number: [57-10-3]
`Synonyms: cetylic acid; hexadecanoic acid; hexadecylic acid.
`Appearance: the pure material is a white, crystalline powder.
`Boiling point: 215°C
`Density: 0.853 g/cm3 at 62°C
`Melting point: 63-64°C
`80 = 1.4273
`Refraciive index: n0
`Solubility: freely soluble in chloroform; ether, propan-2-ol and
`hot etlianol (95%); sparingly soluble in ethanol (95%);
`practically insoluble in water.
`
`Purified stearic acid: C1sH36O2
`Mofeculm· weight: 284-47
`GAS.number: [57-11-4]
`Synonyms: octadecanoic acid.
`Plzarmacopeias; USPNF.
`Acid value: 195-200
`Boiling point: 361 °C
`Density: 0.847 g/cm3 at 70°C
`Flash point: 196°C
`Iodine number: .,;; 1.5
`Melting point: 66-69°C
`80
`1.4299
`Refraclive index: n0
`Solubility: soluble 1 in 5 parts benzene, 1 in 6 parts carbon
`tetrachloride, I in 2 parts chloroform, 1 in I 5 parts ethanol, l
`in 3 parts ether; practically insoluble in water.
`Vapor density (re/ati11e): 9.80 (air = 1)
`Comments: purified stearic acid contains not less than 96.0%
`of stearic and palmitic acid, of which, stearic acid constitutes
`not less than 90.0% of the total.
`
`19. Comments
`A wide range of different grades of stearic acid are
`commercially available which lrnve varying chemical composi(cid:173)
`tions and hence different physical and chemical properties, see
`Table r.< 10>
`
`2.
`
`20. Specific References
`lranloye TA, Parrott EL. Effects of compression force, partide
`I.
`size, and lubricants on dissolution rate. J Phann Sci 1978; 67:
`535-539.
`Jarosz PJ, Parrott EL. Effect of tablet lubricants on axial and
`radial work of failure. Drug Dev Ind Phann 1982; 8: 4450453.
`3. Mitrevej KT, Augsbmger LL. Adhesion of tablets in a rotary
`tablet press II: effects of blending time, running time, and .
`lubricant concentration. Drug Dev Ind Pharm 1982; 8: 237-282.
`4. Musikabhumma P, Rubinstein MH, Khan KA. Evaluation of
`stearic acid and polyethylene glycol as binders for tabletting
`potassium pbenethicillin, Drug Dev Ind Phann 1982; 8: 169- l 88.
`5, Suzuki K. Rheological study of vanishing cream. Cosmet Toilet
`1976; 91(6): 23-31.
`6. Mores LR. Application of stearates in cosmetic creams and
`lotions. Cosmet Toilet. 1980; 95(3): 79, 81-84.
`7. Botha SA, Lotter AP, Compatibility study between naproxen and
`tablet excipients using differential scanning calorililetry. Drug
`Dev Ind Phann 1990; 16: 673-68:i,
`8. Rowe RC, Forse SF. Pitting: a defect on film-coated tablets. Int J
`Pharmaceutics 1983; l7: 347-349.
`9. Sweet DV, editor. Registry of toxic effects of chemical
`substances. Cincinnati: US Department of Health, 1987.
`10. Phadke DS, Keeney MP, Norris DA. Evaluation of batch-to(cid:173)
`batch and manufacturer-to-lilanufacturer variability in
`the
`physical properties of talc and stearic acid. Drng Dev lad
`Pham1 I 994; 20: 859-,871.
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`21. General References
`Pilpel N. Metal stearates in pharmaceuticals and cosmetics. Mfg Chem
`Aerosol News 1971; 42(10): 37-40.
`
`22. Authors
`USA: L V Allen.
`
`Stearic Acid 497
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`

`

`. .
`
`640
`
`Index
`
`Encapsin, 145, 614
`Entonox, 324
`Eosine, 127, 128
`Epikuron, 267, 607, 614, 620
`Equal, 21
`Equil.ibrium moisture content see Labora-
`tory methods
`Erucic acid, 69
`Erythrosine, 126, 127
`Erythrosine ye.llowish Na, 127, 128
`DL-Erythro-9, 10, 16,-trihydroxyhexadecanoic
`acid, 423
`Espholip, 267, 607, 614, 620
`Estergel, 243
`Esto/ 1473, 209, 610, 622
`Esto! 1514, 243, 610, 622
`E.vtol 1517, 245, 610, 622
`Ethal, 99
`[[N,N' -1,2-Ethanediylbis[N-( carboxy(cid:173)
`methyl)glycinato ]]( 4· )·N,N' ,0,0' ,0N,
`-ON']calciate(2-)disodium, 178
`N,N' -1,2-Ethanediylbis[N•( carboxy-
`methyl)glycine], 176
`Dipotassium salt, 177
`Disodium salt, 177
`Tetrasodium salt, 178
`Ethanol, 7
`Dilute, 8
`Ethanol (96%), 7
`Ethanol intoxication, 8
`Ethanolarnine, 319
`1,2-Ethenedicarboxylic acid, 197
`Ethenol homopolymer, 383
`l-Ethenyl-2-pyrrolidinone homopolymer,
`143, 392
`Ethocel, 186, 605, 618
`Ethol, 99
`Ethosperse, 369
`3-Ethoxy•4-hydroxybenzaldehyde, 184
`Ethoxylated fatty acid esters, 379
`Ethyl alcohol, 7
`Ethyl benzene-1,2-dicarboxylate, 167
`Ethyl cellulose, 186
`Ethyl citrate, 540
`Ethyl ester beta-apo-8' carotenoic acid, 126
`Ethyl gallate, 403
`Ethyl hydroxide, 7
`Ethyl hydroxybenzoate, 191
`Etl1yl 4-hydroi,ybenzoate, 191
`Potassium salt, 193
`Sodium salt, 193
`Etl1yl p-hydroxybenzoate, 191
`Ethyl maltol, 180
`Ethyl 9-octadecenoate, 182
`Ethyl oleate, l 82
`Ethyl parahydroxybenzoate, 191
`Ethylparasept, 191
`Ethyl phthala.te, 167
`2-Ethyl pyromeconic acid, 180
`Ethyl (sodium o-mercaptoben-
`zoato )mercury, 526
`Ethyl 3,4,5-trihydroxybenzoate, 403
`Ethyl vanillin, 184
`Ethvlan C, 367
`Etl1ylcellulose, I 86
`Ethylcellulosum, 186
`Ethylene fluoride, 169
`Ethylenebis(iminodiacetic acid),
`Di potassium salt, I 77
`Disodium salt, 177
`Tetrasodium salt, 178
`Ethylenediaminetetraacetic acid, 176
`Calcium disodium chelate, 178
`
`Ethylenediaminetetraacetic acid (Co111inued)
`Dipotassium salt, 177
`Disodium salt, I 77
`Tetrasodium salt, 178
`[(Ethylenedini tdlo )tetraaceta to ]calciate(2·)
`disodium, 178
`(Ethylenedinitrilo)tetraacetic acid, 176
`Dipotassium salt, 177
`Disodium salt, 177
`Tetrasodium salt, 178
`Ethyleneglycol monophenyl ether, 338
`Ethylformic acid, 460
`Sodium salt, hydrate, 459
`N-Ethylglucarnine, 303
`2-Ethyl-3-hydtoxy-4H-pyran-4-one, 180
`Ethyl[2-mercaptobenzoato(2-)-0,S]-mercu-
`rate( 1-) sodium, 526
`Ethyl(2-mercaptobenzoato-S)-mercury,
`sodium salt, 526
`Ethylolamine, 319
`Ethylparaben, 191
`Potassium, 193
`Sodium, 193
`Ethylprotocatechnic aldehyde, 184
`Ewcas 35, 371, 604, 617
`Eudragit, 362, 615
`Euinulgin, 606, 613
`Exameen 3580, 27, 624
`Explotab, 462, 605, 618
`Explotab Low pH; 465
`Exsiccated c11lcium sulfate, 68
`Exsiccated sodium sulfite, 452
`Extended release agents,
`See also coating agents
`Bentonite, 24
`Carbomer, 71
`Glyceryl palmitostearate, 211
`Hydrogenated castor oil, 82
`Polacrilin potassium, 350
`Zein, 568
`
`Fast-Flo, 252, 618
`Fast Flo Lactose 316, 607
`Fast green FCF, 127, 128
`FD&C blue #1, 127
`Lake, 128
`FD&C blue #2, 127, 132
`Lake, 128
`FD&C green #3, 127
`Lake, 128
`FD&C red #3, 127
`FD&C red #4, 127
`Lake, 128
`FD&C red #40, 127
`Lake, 127
`FD&C yellow #5, 133
`Lake, 128
`FD&C yellow #6, 127, 133
`Lake, 128
`Ferric ammonium citrate, 129
`Ferric ammonh1m ferrocyanide, 129
`Ferric ferrocyanide, 129
`Ferric maltol, 292
`Fibrocel, 84, 621
`Fikentscher's equation, 392
`Fillers see Diluents
`Film-coating, see Coating agents
`Film-formers see Coating agents
`Finmalt L, 287, 605, 615
`Fisi:her-Tropsch process, 327
`Flaming red, 127, 128
`Flavor enhancers,
`Citric acid monohydrate, 123
`
`Flavor enhancers (Continued)
`Ethyl maltol, 180
`Maltol, 292
`Tartaric acid, 522
`Flavoring agents,
`Ethyl maltol, 180
`Ethyl vanillin, 184
`Fumaric acid, 197
`Malic acid, 285
`Maltol, 292
`Menthol, 304
`Vanillin, 542
`Flavoxanthin, 126
`Flowability see Laboratory methods
`Fhif1ex W, 483, 616
`Fluidarnid R444P, 489, 609, 615, 621
`Fluorescein, 127, 128
`Fluorocarbon 134a, 524
`Fluorocarbons see Aerosol propellants
`Fluorotrichloromethane, 536
`For/an 200, 334, 621
`Fractionated coconut oil, 299
`Freon 11, 536
`Freon 12, I 60
`Freon 114, 163
`Frige11, 606
`Frigen 11, 536
`Frige1112, 160
`Frigen 22, l19
`Frigen 114, 163
`Frigen 134a, 524
`/3-o-Frnctofuranosyl•(.JC·D•glucopyranoside, 500
`D·(· )-Fructopyranose, 194
`Fructose, 194
`Liquid, 195
`Powdered, 195
`o-Fructose, 194
`/3-o-fructose, I 94
`Fruit sugar, 194
`Fumaric acid, 197
`Octiidecyl ester, sodium salt, 467
`Fumed silica, 424
`Furanose, 194
`
`Galactomannan, 215
`Galactomannan polysaccharide, 215
`4°0-(/3·D•Galactopyranosyl)-o-glucitol, 288
`0-/3-0-Galactopyranosyl-( 1->4)-a-o-gluco-
`pyranose anhydrous, 252
`0-/3-0-Galactopyranosyl-{l->4)-a-o-gluco-
`pyranose monohydrate, 252
`o-Galactose, 215
`4-(/j-o-Galactosido )00-glncose, 252
`/3-Galactosido-sorbitol, 288
`Gallic acid propyl ester, 402
`Gamma cyclodextrin, 145
`Gamma tocopherol, 14
`Gamma W8, 145,610,615, 622
`Garantose, 415
`Gelatin, 199
`Ge.latin capsules, 199
`Gelatina, 199
`Gelatine, 199
`Gell.ing agents see Viscosity-increasing
`agents
`Geloel, 613, 618
`Gelsorb, 269, 603
`Genetron 11, 536
`Ge11etron 12, 160
`Gentron 114, 163
`Gerliw/1 115, 238, 622
`Genna/I fl, 239, 622
`Gingelly oil, 420
`
`Purdue 2026
`Collegium v. Purdue, PGR2018-00048
`
`