`
`Handbook of
`PHARMACEUTICAL
`EXCIPIENTS
`
`
`
`American Pharmaceutical Association
`2215 Constitution Avenue, NW:
`Washington, DC 20037 USA
`
`The Pharmaceutical Society of Great Britain
`1 Lambeth HighStreet
`London SE1 7JN, England
`
`Published by
`
`Cosmo Ex. 2029-p. 1
`Argentum v Cosmo
`IPR2018-00080
`
`Cosmo Ex. 2029-p. 1
`Argentum v Cosmo
`IPR2018-00080
`
`

`

`American Pharmaceutical Association Production Staff
`James C. Boylan
`Jack Cooper
`Zak T. Chowhan
`
`The Pharmaceutical Society of Great Britain Production Staff
`Walter Lund
`Ainley Wade
`Robert F. Weir
`BernardJ. Yates
`
`Publication Production Stait
`Marlene Povich, Art and Production Manager
`Carol Niedzialek, Production Coordinator
`John Covert, Director of Publications
`
`
`
`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 Conventionis not responsible for any inaccuracy of quotation orfor any false or mis-
`leading implication that may arise from separation of an excerptfrom the original context or
`by obsolescenceresulting from publication of a supplement.
`
`Selected structural formulas from The Merck Index, Tenth Edition, 1983, published by Merck
`& Co., Rahway, New Jersey, are reprinted with permission.
`
`© Copyright 1986 by the American Pharmaceutical Association, 2215 Constitution Avenue,
`N.W., Washington, D.C. 20037 USA, and The Pharmaceutical Society of Great Britain, 1 Lam-
`beth High Street, London SE1 7JN,England. No part ofthis 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 (U.S.): 0-917330-56-0
`ISBN (U.K.): 0-85369-164-9
`
`Printed in the USA
`
`Cosmo Ex. 2029-p. 2
`Argentum v Cosmo
`IPR2018-00080
`
`Cosmo Ex. 2029-p. 2
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`IPR2018-00080
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`

`

`
`
`Lecithin
`
`. Nonproprietary Name
`NF: Lecithin
`
`. Functional Categories
`USP: Emulsifying and/orsolubilizing agent.
`Others: wetting and dispersing agent; emollient, digestible
`surfactant; moisturizer
`
`. Synonyms
`Soybean phospholipids; mixed soybean phosphatides; soy-
`bean lecithin; vegetable lecithin; egg lecithin; ovolecithin.
`
`. Chemical Name and CAS Registry Number
`Phosphatidylcholine—commercially, a mixture of phos-
`phatidylcholine, phosphatidylethanolamine, phosphatidyl-
`inositol, phytoglycolipids, other phosphatides, carbohy-
`drates, triglycerides and other components. [8002-43-S]
`
`. Empirical Formula
`
`Molecular Weight
`
`. Structural Formula
`
`8—phosphatidylcholine
`
`GHz0cOR
`o7
`rocon
`+
`C20 —P ~— OCH)CH N(CH)
`\,
`a—phosphatidylcholine
`. Commercial Availability
`USA
`American Lecithin
`Central Soya Co.
`Spencer-Kellogg
`UK
`Alembic (Lovelock) Products
`Steetley Chemicals, Ltd.
`. Method of Manufacture
`Crude soybeanlipids are obtained bythesolventextraction
`of soybeans. Lecithin is obtained as a water extract of these
`crude soybeanlipids. 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 ‘egg, known as egg lecithin. Synthetic
`lecithins are also made.
`
`. Description
`Lecithin is brown to light yellow, depending on whetheritis
`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 onthefree fatty
`acid content.
`
`10.
`
`Pharmacopeial Specifications
`Hest
`Water (method 1)
`Arsenic
`Lead
`Heavy metals (methodIl)
`Acid value
`
`NE
`1.5%
`3 ppm
`0.001%
`=0,004%
`736
`
`Lecithin
`
`165
`
`Ll.
`
`12.
`
`13.
`
`14.
`
`15.
`
`16.
`
`17.
`
`Test
`Hexane-insoluble matter
`Acetane-insoluble matter
`
`NE
`<0.3%
`=50.0%
`
`Typical Properties
`Isoelectric point: Approximately 3.5
`Miscibility: When mixed with water, lecithin hydrates to
`form an emulsion. It 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, mineraloil and fatty acid. Insol-
`uble in polar solvents and water. Practically insoluble in cold
`vegetable and animaloils.
`Physical form: Liquid or granule (oil-free lecithin)
`Density: Liquid lecithin, 0.97 g/cm}; granule lecithin, 0.5 g/
`cm
`lodine value: Liquid lecithin, 95-100; granule lecithin, 82-88
`Saponification 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 moisture
`pickup, Lecithin is subject to microbial degradation. Expo-
`sure to light should be avoided.A shelflife of several years
`can be expected whenstored at ambient temperatures.
`Incompatibilities
`Lecithin decomposes at extreme pH. When heated,it oxi-
`dizes, darkens and decomposes. It is hydrolyzed by ester-
`ases.
`
`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.
`
`20.
`
`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 che
`active ingredientor formulation excipients may occur.
`Specific References
`In “Encyclopedia of Chemical
`1. P Sartoretto, Lecithin.
`Technology,” 2nd Ed., Kirk & Othmer 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.
`
`Cosmo Ex. 2029-p. 3
`USA: W. Han*; A. Palmieri**; A. L, Monaco” Argentum v Cosmo
`IPR2018-00080
`
`Cosmo Ex. 2029-p. 3
`Argentum v Cosmo
`IPR2018-00080
`
`