`
`Handbook of
`PHARMACEUTICAL
`
`EXCIPIENTS
`
`
`
`ll, ‘
`
`American Pharmaceutical Association
`2215 ConStitution Avenue, NW
`Washington, DC 20037 USA
`
`Published by
`
`'
`
`The Pharmaceutical Society of Grear Britain
`1 Lambetl} High Street
`London SE1 UN, England
`
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`Cosmo Ex. 2029-p. 1
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`

`American Pharmaceutical Association Production Staff
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`james C. Boylan
`Jack Cooper
`Zak T. Chowhan
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`The Pharmaceutical Society of Great Britain Production Stafl'
`Walter Lund
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`Ainley Wade
`Robert F. Weir
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`Bernard J. Yates
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`Publication Production Staff
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`Library of Congress Data
`
`The use of portions of the text of USP XXI/NF XVI is by permission of the USP Convention,
`Inc. The Convention is not responsible for any inaccuracy of quotation or for any false or mis-
`leading implication that may arise from separation of an excerpt from the original context or
`by obsolescence resulting from publication of a supplement.
`
`Selected structural formulas from The Merck Index, Tenth Edition, 1983, published by Merck
`51 Co., Rahway, New Jersey. are reprinted with permission.
`
`© Copyright 1986 by the American Pharmaceutical Association, 2215 Constitution Avenue,
`NW, Washington, DC. 20037 USA, and The PharmaceuticalSociety of Great Britain.l Lam-
`beth High Street, London 551 UN, England. N0 part of this publication may be reproduced or
`transmitted in any form or by any means, electronic or mechanical, including photocopy, re~
`cording,.,or any information Storage or retrieval system,without prior Written permission from
`the joint publishers.
`
`ISBN (us): 0-917330-56—0
`ISBN (we): 0~85369~164-9
`
`Printed in the USA
`
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`

`
`
`Lecithin
`
`l. Nonproprietary Name
`NF: Lecithin
`
`2. Functional Categories
`USP: Emulsifying and/or solubilizing agent.
`Others: wetting and dispersing agent; emollient; digestible
`surfactant; moisturizer
`
`3. Synonyms
`Soybean phospholipids; mixed soybean phosphatides; soy-
`bean lecithin; vegetable lecithin; egg lecithin: ovolecithin.
`
`4. Chemical Name and CAS Registry Number
`Phosphatidylcholine—commercially, a minute of phos-
`phatidylcholine. phosphatidylethanolamine, phosphatidyl—
`inositol, phyroglycolipids. other phosphatides, carbohy-
`drates. triglycerides and orher components. [8002-43-5]
`
`5. Empirical Formula
`
`Molecular Weight
`
`6. Structural Formula
`
`cuzomn
`0"
`éBOCOR
`+
`/
`I
`cazo —-p - OCH2GI2MCH3)3
`O
`
`a—phosphatidylcholine
`
`fifiphosphatidylcholine
`
`7. Commercial Availability
`USA
`American Lecithin
`
`Central Soya Co.
`Spencer-Kellogg
`UK
`
`Alembic (Lovelock) Producrs
`Steetley Chemicals. Ltd.
`8. Method of Manufacture
`
`Crude soybean lipids are obtained by the solvent extraction
`of soybeans. Lecithin is obtained as a water extract of these
`crude soybean lipids. This crude lecithin is then upgraded by
`various techniques. Lecithin can also be made from corn.
`peanut, cottonseed, Castor seed and coffee beans. It has
`been made from 'eg. known as eg lecithin. Synthetic
`lecithins are also made.
`
`9. Description
`Lecithin is brown to light yellow, depending on whether it is
`unbleached or bleached. It has practically no odor and a
`bland to nut—like taste, similar to soybean oil. In consistency,
`it may vary from plastic to fluid depending on the free fatty
`acid content.
`
`10. Pharmacopeial Specifications
`Test
`
`Water (method I)
`Arsenic
`Lead
`
`Heavy metals (method 11)
`Acid value
`
`NF
`
`51.5%
`53 ppm
`30.00196
`
`50.00496
`536
`
`Lecithin
`
`165
`
`ll.
`
`12.
`
`l3.
`
`14.
`
`15.
`
`16.
`
`17.
`
`Test
`Hexane—insoluble matter
`Acetane-insoluble matter
`
`.
`NF
`50.3% .
`550.0%
`
`Typical Properties
`isoeleciric point: Approximately 3.5
`Miscibility: When mixed with water, lecithin hydrates to
`form an emulsion. lt readily forms imbibitions (taking up
`liquid without a measurable increase in volume) with almost
`any solvent.
`pH: Approx. 6.6 (soybean phosphatides)
`Solubility: Soluble in aliphatic and aromatic hydrocarbons.
`halogenated hydrocarbons, mineral oil and fatty acid. Insol-
`uble in polar solvents and water. Practically insoluble in cold
`vegetable and animal oils.
`Physical form: Liquid or granule (oil-free lecithin)
`Denssiiy: Liquid lecithin, 0.97 g/cm’; granule lecithin. 0.5 g/
`cm
`
`Iodine value: Liquid lecithin. 95-100; granule lecithin. 82-88
`Saponificaiion value: 196
`
`Stability and Storage Conditions
`Fluid lecithin grades should be stored at room temperature
`or above (22°49°C) in well~closed containers. Tempera-
`tures of 160—180°C will cause degradation within 24 hours.
`Temperatures below 10°C may cause separation. Lecithins
`are hygroscopic; keep containers closed to prevent moisrure
`pickup. Lecithin is subject to microbial degradation. Expo-
`sure to light should be avoided. A shelf life of several years
`can be expected when Stored at ambient temperamres.
`
`Incompatibilities
`Lecithin decomposes at extreme pH. When heated. it oxi-
`dizes. darkens and decomposes. It is hydrolyzed by esrer-
`3565
`
`Safety
`Lecithin is recognized as a multiple purpose food substance
`by the FDA.
`
`Handling Precautions
`
`Regulatory Status
`NF XVI
`
`Applications in Pharmaceutical Formulation or
`Technology
`Lecithins are used as dispersing and emulsifying agents for
`intramuscular injections. They are used in creams and
`ointments as dispersing, wetting, emulsifying and emollient
`agents.
`
`18.
`
`Related Substances
`
`19.
`
`Comments
`
`Since lecithin contains a variety of unspecified materials,
`care should be exercised in the use of unpurified lecithin in
`injectable or topical dosage forms, as interaction with the
`aCtive ingredient or formulation excipients may occur.
`
`20
`
`. Specific References
`In “Encyclopedia of Chemical
`1. P. Sartoretto, Lecithin.
`Technology," 2nd Ed., Kirk 6! Otbmer eds. Vol. 12,
`John Wiley and Sons, Inc, 1967, New York, p. 343.
`2. G. B. Ansell and J. N. Hawthorne, "Phospholipids," El-
`sevier, New York, 1964.
`
`USA: W. Han“; A. Palmieri“; A. L. Monaco’
`
`Cosmo Ex. 2029-p. 3
`Argentum v Cosmo
`|PR2018-00080
`
`Cosmo Ex. 2029-p. 3
`Argentum v Cosmo
`IPR2018-00080
`
`