Handbook of Handbook of
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`PHARMACEUTICAL PHARMACEUTICAL
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`EXCIPIENTS EXCIPIENTS
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`NOVARTIS EXHIBIT 2005
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`/ > / >
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`/Handbook of /Handbook of
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`PHARMACEUTICAL PHARMACEUTICAL
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`EXCIPIENTS 7 / ' EXCIPIENTS 7 / '
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`e;7 e;7
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`Second Edition Second Edition
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`Edited by Edited by
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`Ainley Wade and Paul J Weller Ainley Wade and Paul J Weller
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`American Pharmaceutical Association American Pharmaceutical Association
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`Washington Washington
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`1994 1994
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`The Pharmaceutical Press The Pharmaceutical Press
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`London London
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`8980 8980
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`18.6 18.6
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`NOVARTIS EXHIBIT 2005
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`© Copyright 1986, 1994 by the American Pharmaceutical Association, 2215 Constitution Avenue NW, Washington, © Copyright 1986, 1994 by the American Pharmaceutical Association, 2215 Constitution Avenue NW, Washington,
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`DC 20037-2985, USA, and The Pharmaceutical Press, Royal Pharmaceutical Society of Great Britain, 1 Lambeth High DC 20037-2985, USA, and The Pharmaceutical Press, Royal Pharmaceutical Society of Great Britain, 1 Lambeth High
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`Street, London, SEl 7JN, England. Street, London, SEl 7JN, England.
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`
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`A catalogue record for this book is available from the British Library. A catalogue record for this book is available from the British Library.
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`Library of Congress Catalog Card Number: 94-79492. Library of Congress Catalog Card Number: 94-79492.
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`I I
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`1-+ <,.t;1 1-+ <,.t;1
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`{ {
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`International Standard Book Number (ISBN) in the UK: 0 85369 305 6 International Standard Book Number (ISBN) in the UK: 0 85369 305 6
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`International Standard Book Number (lS13N) in the USA: 091730668 International Standard Book Number (lS13N) in the USA: 091730668
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`No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical,
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`including photocopy, recording, or any information storage or retrieval system, without prior written permission from including photocopy, recording, or any information storage or retrieval system, without prior written permission from
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`the joint publishers. the joint publishers.
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`Typeset in Great Britain by Alden Multimedia, Northampton. Typeset in Great Britain by Alden Multimedia, Northampton.
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`Printed and bound in Great Britain by Printed and bound in Great Britain by
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`NOVARTIS EXHIBIT 2005
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`Corn Oil Corn Oil
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`1. Nonproprietary Names 1. Nonproprietary Names
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`USPNF: Corn oil USPNF: Corn oil
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`2. Synonyms 2. Synonyms
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`Calchem IVO-lOS; Lipex 104; maize oil. Calchem IVO-lOS; Lipex 104; maize oil.
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`3. Chemical Name and CAS Registry Number 3. Chemical Name and CAS Registry Number
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`Corn oil [8001-30-7] Corn oil [8001-30-7]
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`4. Empirical Formula Molecular Weight 4. Empirical Formula Molecular Weight
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`Corn oil is composed of fatty acid esters with glycerol, known Corn oil is composed of fatty acid esters with glycerol, known
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`commonly as triglycerides. Typical corn oil produced in the commonly as triglycerides. Typical corn oil produced in the
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`US contains five major fatty acids: linoleic 58.9%; oleic 25.8%; US contains five major fatty acids: linoleic 58.9%; oleic 25.8%;
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`palmitic 11.0%; stearic 1.7% and linolenic 1.1 %. Corn grown palmitic 11.0%; stearic 1.7% and linolenic 1.1 %. Corn grown
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`outside the US corn belt, including other countries, yields corn outside the US corn belt, including other countries, yields corn
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`oil with lower linoleic, higher oleic and higher saturated fatty oil with lower linoleic, higher oleic and higher saturated fatty
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`acid levels. Corn oil also contains small quantities of plant acid levels. Corn oil also contains small quantities of plant
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`sterols. sterols.
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`5. Structural Formula 5. Structural Formula
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`See Section 4. See Section 4.
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`6. Functional Category 6. Functional Category
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`Oleaginous vehicle; solvent. Oleaginous vehicle; solvent.
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`7. Applications in Pharmaceutical Formulation or
`7. Applications in Pharmaceutical Formulation or
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`Technology Technology
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`Corn oil is used primarily in pharmaceutical formulations as a Corn oil is used primarily in pharmaceutical formulations as a
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`solvent for intramuscular injections or as a vehicle for topical solvent for intramuscular injections or as a vehicle for topical
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`preparations. Emulsions containing up to 67% corn oil are preparations. Emulsions containing up to 67% corn oil are
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`also used as oral nutritional supplements, see also Section 19. also used as oral nutritional supplements, see also Section 19.
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`Corn oil has a long history of use as an edible oil. Corn oil has a long history of use as an edible oil.
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`8. Description 8. Description
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`Clear, light yellow colored, oily liquid with a faint character(cid:173)Clear, light yellow colored, oily liquid with a faint character(cid:173)
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`istic odor and slightly nutty, sweet taste resembling cooked istic odor and slightly nutty, sweet taste resembling cooked
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`sweet corn. sweet corn.
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`9. Pharmacopeial Specifications 9. Pharmacopeial Specifications
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`Test Test
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`Specific gravity Specific gravity
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`Heavy metals Heavy metals
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`Cottonseed oil Cottonseed oil
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`Fatty acid composition Fatty acid composition
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`Free fatty acids Free fatty acids
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`Iodine value Iodine value
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`Saponification value Saponification value
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`Unsaponifiable matter Unsaponifiable matter
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`USPNF XVII USPNF XVII
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`0.914-0.921 0.914-0.921
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`~ 0.001% ~ 0.001%
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`+ +
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`+ +
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`+ +
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`102-130 102-130
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`187-193 187-193
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`~ I.S% ~ I.S%
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`10. Typical Properties 10. Typical Properties
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`Acid value: 2-6 Acid value: 2-6
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`Autoignition temperature: 393 DC Autoignition temperature: 393 DC
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`Density: see HPE Data. Density: see HPE Data.
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`Flash point: 321 DC Flash point: 321 DC
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`Hydroxyl value: 8-12 Hydroxyl value: 8-12
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`Corn Oil 135 Corn Oil 135
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`Melting point: -18 to -IOOC Melting point: -18 to -IOOC
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`Refractive index: Refractive index:
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`nD25 = 1.470-1.474; nD25 = 1.470-1.474;
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`nD40 = 1.464-1.468. nD40 = 1.464-1.468.
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`Solubility: slightly soluble in ethanol (95%); miscible with Solubility: slightly soluble in ethanol (95%); miscible with
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`benzene, chloroform, ether and hexane. benzene, chloroform, ether and hexane.
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`Viscosity (dynamic): see HPE Data. Viscosity (dynamic): see HPE Data.
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`Density Density
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`Viscosity Viscosity
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`HPE Laboratory Project Data HPE Laboratory Project Data
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`Results Results
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`0.918 g/cm3 (a) 0.918 g/cm3 (a)
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`0.915 g/cm3 (b) 0.915 g/cm3 (b)
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`38.83 mPa s (a) 38.83 mPa s (a)
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`37.36 mPas (b) 37.36 mPas (b)
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`Method Method
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`DE-5 DE-5
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`DE-5 DE-5
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`VIS-2 VIS-2
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`VIS-2 VIS-2
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`Lab # Lab #
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`30 30
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`30 30
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`30 30
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`30 30
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`Supplier: a. Welch, Holme & Clark Co; b. Capital. Supplier: a. Welch, Holme & Clark Co; b. Capital.
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`11. Stability and Storage Conditions 11. Stability and Storage Conditions
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`Corn oil is stable when protected with nitrogen in tightly Corn oil is stable when protected with nitrogen in tightly
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`sealed bottles. On prolonged exposure to air it thickens and sealed bottles. On prolonged exposure to air it thickens and
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`becomes rancid. Corn oil may be sterilized by dry heat, becomes rancid. Corn oil may be sterilized by dry heat,
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`maintaining it at 150°C for one hour,o) maintaining it at 150°C for one hour,o)
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`Corn oil should be stored in an airtight, light-resistant Corn oil should be stored in an airtight, light-resistant
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`container in a cool, dry, place. container in a cool, dry, place.
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`12. Incompatibilities 12. Incompatibilities
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`13. Method of Manufacture 13. Method of Manufacture
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`Refined corn oil is obtained from the germ or embryo of Zea Refined corn oil is obtained from the germ or embryo of Zea
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`mays Linne (Fam. Gramineae) which contains nearly 50% of mays Linne (Fam. Gramineae) which contains nearly 50% of
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`the fixed oil, compared with 3.0-6.5% in the whole kernel. The the fixed oil, compared with 3.0-6.5% in the whole kernel. The
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`oil is obtained from the embryo by expression and/or solvent oil is obtained from the embryo by expression and/or solvent
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`extraction. The crude oil is then refined to remove free fatty extraction. The crude oil is then refined to remove free fatty
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`acids, phospholipids and impurities. It is bleached with solid acids, phospholipids and impurities. It is bleached with solid
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`adsorbents to lighten its color, dewaxed by chilling (which adsorbents to lighten its color, dewaxed by chilling (which
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`removes any solid waxy components) and deodorized at high removes any solid waxy components) and deodorized at high
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`temperature, under vacuum, to produce a bland, odorless, temperature, under vacuum, to produce a bland, odorless,
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`edible product. edible product.
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`14. Safety 14. Safety
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`Based upon its extensive history of food usage corn oil is Based upon its extensive history of food usage corn oil is
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`generally regarded as a nontoxic and nonirritant material. generally regarded as a nontoxic and nonirritant material.
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`15. Handling Precautions 15. Handling Precautions
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`Observe normal precautions appropriate to the circumstances Observe normal precautions appropriate to the circumstances
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`and quantity of material handled. Spillages of this material are and quantity of material handled. Spillages of this material are
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`very slippery and should be covered with an inert absorbent very slippery and should be covered with an inert absorbent
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`material prior to disposal. material prior to disposal.
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`16. Regulatory Status 16. Regulatory Status
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`Included in the FDA Inactive Ingredients Guide (1M Included in the FDA Inactive Ingredients Guide (1M
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`injections, oral capsules, suspensions, tablets and topical injections, oral capsules, suspensions, tablets and topical
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`emulsions). emulsions).
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`17. Pharmacopeias 17. Pharmacopeias
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`Cz, Egypt, Fr, Jpn, Mex and USPNF. Cz, Egypt, Fr, Jpn, Mex and USPNF.
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`18. Related Substances 18. Related Substances
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`Canola Oil; Cottonseed Oil; Peanut Oil; Sesame Oil; Soybean Canola Oil; Cottonseed Oil; Peanut Oil; Sesame Oil; Soybean
`Oil.
`Oil.
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`136 Corn Oil
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`19. Comments
`Corn oil contains a high content of unsaturated acids and has
`been used to replace fats and oils containing a high content of
`saturated acids in the diets of patients with hypercholester(cid:173)
`olemia.
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`20. Specific References
`I. Pasquale D, Jaconia D, Eisman P, Lachman L. A study of
`sterilizing conditions for injectable oils. Bull Parenter Drug Assoc
`1964; 18(3): I-II.
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`21. General References
`Mann JI, Carter R, Eaton P. Re-heating corn oil does not saturate its
`double bonds [letter]. Lancet 1977; ii: 401.
`Strecker LR, Maza A, Winnie GF. Corn oil - composition, processing
`and utilization. In: Erickson DR, editor. World conference
`proceedings. Edible fats and oils processing: basic principles and
`modern practices. American Oil Chemist's Society, 1990: 309-323.
`Watson SA, Ramstead PE, editors. Corn chemistry and technology.
`St. Paul: American Association of Cereal Chemists Inc, 1987: 53-
`78.
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`22. Authors
`USA: KD Brenner.
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