Hypromellose Acetate Succinate
Poly(methylvinyl ether/maleic anhydride)
Sulfobutylether b-Cyclodextrin
d-Alpha tocopheryl acid succinate
dl-Alpha tocopheryl acid succinate
Bacteriostatic water for injection
Diethylene glycol monopalmitostearate
Dodecyltrimethylammonium bromide
Hexadecyltrimethylammonium bromide
Hydrogenated vegetable oil, type II
2-Hydroxypropyl-b-cyclodextrin
3-Hydroxypropyl-b-cyclodextrin
Magnesium trisilicate anhydrous
Microcrystalline cellulose and carboxymethylcellulose sodium
Microcrystalline cellulose and carrageenan
Microcrystalline cellulose and guar gum
Self-emulsifying glyceryl monostearate
Trimethyltetradecylammonium bromide
Pharmaceutical dosage forms contain both pharmacologically
active compounds and excipients added to aid the formulation
form (i.e. its bioavailability and stability) are, for the most part,
highly dependent on the excipients chosen, their concentration
and interaction with both the active compound and each other.
No longer can excipients be regarded simply as inert or inactive
ingredients, and a detailed knowledge not only of the physical
and chemical properties but also of the safety, handling and
regulatory status of these materials is essential for formulators
throughout the world. In addition, the growth of novel forms of
delivery has resulted in an increase in the number of the
improve their properties. The Handbook of Pharmaceutical
Excipients has been conceived as a systematic, comprehensive
resource of information on all of these topics
The first edition of the Handbook was published in 1986 and
contained 145 monographs. This was followed by the second
edition in 1994 containing 203 monographs, the third edition
in 2000 containing 210 monographs and the fourth edition in
2003 containing 249 monographs. Since 2000, the data has
also been available on CD-ROM, updated annually, and from
compiled by over 120 experts in pharmaceutical formulation or
excipient manufacture from Australia, Europe, India and the
USA. All the monographs have been reviewed and revised in the
light of current knowledge. There has been a greater emphasis
on including published data from primary sources although
some data from laboratory projects included in previous
editions have been retained where relevant. Variations in test
methodology can have significant effects on the data generated
(especially in the case of the compactability of an excipient),
and thus cause confusion. As a consequence, the editors have
been more selective in including data relating to the physical
properties of an excipient. However, comparative data that
show differences between either source or batch of a specific
excipient have been retained as this was considered relevant to
the behavior of a material in practice. The Suppliers Directory
(Appendix I) has also been completely updated with many more
international suppliers included.
In a systematic and uniform manner, the Handbook of
Pharmaceutical Excipients collects essential data on the
physical properties of excipients such as: boiling point, bulk
and tap density, compression characteristics, hygroscopicity,
Handbook contains information from various international
All of the monographs in the Handbook are thoroughly
cross-referenced and indexed so that excipients may be
identified by either a chemical, a nonproprietary, or a trade
name. Most monographs list related substances to help the
formulator to develop a list of possible materials for use in a
new dosage form or product. Related substances are not
directly substitutable for each other but, in general, they are
excipients that have been used for similar purposes in various
pharmaceutical excipients, and is an essential reference source
for those involved in the development, production, control, or
Handbook of Pharmaceutical Excipients will also be of value to
persons with an interest in the formulation or production of
confectionery, cosmetics, and food products.
The information consists of monographs that are divided into
22 sections to enable the reader to find the information of
interest easily. Although it was originally intended that each
monograph contain only information about a single excipient,
it rapidly became clear that some substances or groups of
substances should be discussed together. This gave rise to such
monographs as ‘Coloring Agents’ and ‘Hydrocarbons’. In
addition, some materials have more than one monograph
depending on the physical characteristics of the material, e.g.
3 Chemical Name and CAS Registry Number
4 Empirical Formula and Molecular Weight
7 Applications in Pharmaceutical Formulation or
9 Pharmacopeial Specifications
11 Stability and Storage Conditions
Descriptions of the sections appear below with information
from an example monograph if needed.
Section 1, Nonproprietary Names, lists the excipient names
Section 2, Synonyms, lists other names for the excipient,
including trade names used by suppliers (shown in italics).
The inclusion of one supplier’s trade name and the absence of
others should in no way be interpreted as an endorsement of
one supplier’s product over the other. The large number of
suppliers internationally makes it impossible to include all the
excipient along with the chemical name, e.g., Acacia [9000-
Sections 4 and 5, Empirical Formula and Molecular Weight
and Structural Formula, are self-explanatory. Many excipients
Section 6, Functional Category, lists the function(s) that an
excipient is generally thought to perform, e.g., diluent, emulsifying agent, etc.
Section 9, Pharmacopeial Specifications, briefly presents the
compendial standards for the excipient. Information included
is obtained from the British Pharmacopoeia (BP), European
Pharmacopeia (PhEur), Japanese Pharmacopeia (JP), and the
United States Pharmacopeia/National Formulary (USP/
USPNF). Information from the JP, USP and USPNF are
included if the substance is in those compendia. Information
from the PhEur is also included. If the excipient is not in the
PhEur but is included in the BP, information is included from
the BP. Pharmacopeias are continually updated with most
now being produced as annual editions. However, although
efforts were made to include up-to-date information at the
time of publication of this edition, the reader is advised to
consult the most current pharmacopeias or supplements.
data are for measurements made at 208C unless otherwise
indicated. Where the solubility of the excipient is described in
words, the following terms describe the solubility ranges:
Very soluble 1 part in less than 1
Sparingly soluble 1 part in 30–100
Slightly soluble 1 part in 100–1000
Very slightly soluble 1 part in 1000–10 000
Practically insoluble 1 part in more than 10 000
Where practical, data typical of the excipient or comparative
data representative of different grades or sources of a material
are included, the data being obtained from either the primary or
the manufacturers’ literature. In previous editions of the
Handbook a laboratory project was undertaken to determine
data for a variety of excipients and in some instances this data
has been retained. For a description of the specific methods
Section 11, Stability and Storage Conditions, describes the
conditions under which the bulk material as received from
the supplier should be stored. In addition some monographs
report on storage and stability of the dosage forms that contain the excipient.
active ingredients. If an incompatibility is not listed it does
not mean it does not occur but simply that it has not been
reported or is not well known. Every formulation should be
tested for incompatibilities prior to use in a commercial product.
Section 13, Method of Manufacture, describes the common
methods of manufacture and additional processes that are
used to give the excipient its physical characteristics. In some
cases the possibility of impurities will be indicated in the
Section 14, Safety, describes briefly the types of formulations
in which the excipient has been used and presents relevant
data concerning possible hazards and adverse reactions that
have been reported. Relevant animal toxicity data are also
Section 15, Handling Precautions, indicates possible hazards
familiarity with current good laboratory practice (GLP) and
current good manufacturing practice (GMP) and standard
chemical handling procedures is assumed.
Section 16, Regulatory Status, describes the accepted uses in
foods and licensed pharmaceuticals where known. However,
the status of excipients varies from one nation to another,
and appropriate regulatory bodies should be consulted for
Section 17, Related Substances, lists excipients similar to the
excipient discussed in the monograph.
Section 18, Comments, includes additional information and
observations relevant to the excipient. Where appropriate, the
Section 19, Specific References, is a list of references cited
Section 20, General References, lists references which have
general information about this type of excipient or the types
of dosage forms made with these excipients.
the monograph are shown in previous printed editions of the
Section 22, Date of Revision, indicates the date on which
changes were last made to the text of the monograph.
A publication containing so much detail could not be produced
without the help of a large number of pharmaceutical scientists
based world-wide. The voluntary support of over 120 authors
has been acknowledged as in previous editions, but the current
editors would like to thank them all personally for their
contribution. Grateful thanks also go to the members of the
International Steering Committee who advised the editors and
publishers on all aspects of the Handbook project. Steering
Committee members also diligently reviewed all of the
monographs before their publication. Many authors and
Steering Committee members have been involved in previous
editions of the Handbook. For others, this was their first edition
although not, we hope, their last. Walter Chambliss and John
Hogan retired from the International Steering Committee
during the preparation of this edition and we extend our
thanks for their support over many years. Thanks are also
extended to excipient manufacturers and suppliers who
provided helpful information on their products.
Thanks are also gratefully extended to the staff of the
Pharmaceutical Press and American Pharmacists Association
who were involved in the production of the Handbook: Eric
Connor, Tamsin Cousins, Simon Dunton, Laurent Galichet,
Julian Graubart, Louise McIndoe, Karl Parsons, Paul Weller,
and John Wilson. Once again, the diligent copy-editing and
challenging questions asked by Len Cegielka helped the authors
and editors, we hope, to express their thoughts clearly,
Raymond C Rowe, Paul J Sheskey and Siaˆ n C Owen
The Handbook of Pharmaceutical Excipients is a reference
work containing a compilation of information on the uses and
properties of pharmaceutical excipients, and the reader is
assumed to possess the necessary knowledge to interpret the
information that the Handbook contains. The Handbook of
Pharmaceutical Excipients has no official status and there is no
intent, implied or otherwise, that any of the information
presented should constitute standards for the substances. The
inclusion of an excipient, or a description of its use in a
particular application, is not intended as an endorsement of
application, may not necessarily prevent its use in other
formulation is efficacious and safe to use.
While considerable efforts were made to ensure the accuracy
of the information presented in the Handbook, neither the
publishers nor the compilers can accept liability for any errors
or omissions. In particular, the inclusion of a supplier within the
Suppliers Directory is not intended as an endorsement of that
supplier or its products and, similarly, the unintentional
omission of a supplier or product from the directory is not
intended to reflect adversely on that supplier or its product.
Although diligent effort was made to use as recent
compendial information as possible, compendia are frequently
revised and the reader is urged to consult current compendia, or
supplements, for up-to-date information, particularly as efforts
are currently in progress to harmonize standards for excipients.
Data presented for a particular excipient may not be
representative of other batches or samples.
Relevant data and constructive criticism are welcome and
may be used to assist in the preparation of any future editions
or electronic versions of the Handbook. The reader is asked to
send any comments to the Editor, Handbook of Pharmaceutical
Excipients, Royal Pharmaceutical Society of Great Britain, 1
Lambeth High Street, London SE1 7JN, UK, or Editor,
Ash M, Ash I. Handbook of Pharmaceutical Additives, 2nd
edn. Endicott, NY: Synapse Information Resources, 2002.
Aulton ME, ed. Pharmaceutics: the Science of Dosage Form
Design, 2nd edn. Edinburgh: Churchill Livingstone, 2002.
Banker GS, Rhodes CT, eds. Modern Pharmaceutics, 4th edn.
New York: Marcel Dekker, 2002.
British Pharmacopoeia 2004. London: The Stationery Office,
European Pharmacopoeia, 5th edn. and supplements. Strasbourg: Council of Europe, 2005.
Florence AT, Salole EG, eds. Formulation Factors in Adverse
Reactions. London: Butterworth, 1990.
Food and Drug Administration. Inactive Ingredient Guide.
http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm
Food Chemicals Codex, 4th edn. Washington, DC: National
Health and Safety Executive. EH40/2002: Occupational
Exposure Limits 2002. Sudbury: Health and Safety Executive, 2001.
Health Canada. Canadian List of Acceptable Non-medicinal
Ingredients. http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd-dpsn/
nmi_list1_e.html (accessed 11 July 2005)
Hoepfner E, Reng A, Schmidt PC, eds. Fiedler Encyclopedia of
Excipients for Pharmaceuticals, Cosmetics and Related
Areas. Aulendorf, Germany: Editio Cantor, 2002.
Japanese Pharmacopeia, 14th edn. and supplement. Tokyo:
Kemper FH, Luepke N-P, Umbach W, eds. Blue List Cosmetic
Ingredients. Aulendorf, Germany: Editio Cantor, 2000.
Lewis RJ, ed. Sax’s Dangerous Properties of Industrial
Materials, 11th edn. New York: John Wiley, 2004.
Lund W, ed. The Pharmaceutical Codex: Principles and
Practice of Pharmaceutics, 12th edn. London: Pharmaceutical Press, 1994.
National Library of Medicine. TOXNET.
http://toxnet.nlm.nih.gov (accessed 11 July 2005)
O’Neil MJ, Smith A, Heckelman PE, eds.The Merck Index: an
Encyclopedia of Chemicals, Drugs, and Biologicals, 13th
edn. Whitehouse Station, NJ: Merck, 2001.
Smolinske SC. Handbook of Food, Drug and Cosmetic
Excipients. Boca Raton, FL: CRC Press, 1992.
Swarbrick J, Boylan JC, eds. Encyclopedia of Pharmaceutical
Technology, 2nd edn. New York: Marcel Dekker, 2002.
Sweetman SC, ed. Martindale: the Complete Drug Reference,
34rd edn. London: Pharmaceutical Press, 2005.
United States Pharmacopeia 28 and National Formulary 23.
and supplement. Rockville, MD: United States Pharmacopeial Convention, 2005.
University of the Sciences in Philadelphia. Remington: the
Science and Practice of Pharmacy, 21st edn. Baltimore:
Lippincott Williams and Wilkins, 2005.
Weiner ML, Kotkoskie LA, eds. Excipient Toxicity and Safety.
New York: Marcel Dekker, 2000.
The titles of journals are abbreviated according to the general style of the Index Medicus.
BS British Standard (specification).
BSI British Standards Institution.
CAS Chemical Abstract Service.
cmc critical micelle concentration.
CTFA Cosmetic, Toiletry, and Fragrance Association.
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