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, flowability, melting point, moisture content, moisture-absorp- tion isotherms, particle size distribution, rheology, specific surface area, and solubility. Scanning electron microphoto- graphs (SEMs) are also included for many of the excipients. The Handbook contains information from various international sources and personal observation and comments from mono- graph authors, steering committee members, and the editors.

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 dosage forms.

The Handbook of Pharmaceutical Excipients is a compre- hensive, uniform guide to the uses, properties, and safety of pharmaceutical excipients, and is an essential reference source for those involved in the development, production, control, or regulation of pharmaceutical preparations. Since many phar- maceutical excipients are also used in other applications, the 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.

Arrangement

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. Starch versus Pregelatinized Starch. Regardless of the complex- ity of the monograph they are all divided into 22 sections as follows:

Nonproprietary Names

Synonyms

Chemical Name and CAS Registry Number

Empirical Formula and Molecular Weight

Structural Formula

Functional Category

Applications in Pharmaceutical Formulation or Technology

Description

Pharmacopeial Specifications

Typical Properties

Stability and Storage Conditions

Incompatibilities

Method of Manufacture

Safety

Handling Precautions

Regulatory Status

Related Substances

Comments

Specific References

General References

Authors

Date of Revision

Descriptions of the sections appear below with information from an example monograph if needed.

Section 1, Nonproprietary Names, lists the excipient names used in the current British Pharmacopoeia, European Pharma- copeia, Japanese Pharmacopeia, and the United States Phar- macopeia/National Formulary.

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 trade names.

Section 3, Chemical Name and CAS Registry Number, indi- cates the unique Chemical Abstract Services number for an

excipient along with the chemical name, e.g., Acacia [9000- 01-5].

Sections 4 and 5, Empirical Formula and Molecular Weight and Structural Formula, are self-explanatory. Many excipients are not pure chemical substances, in which case their compo- sition is described either here or in Section 8.

Section 6, Functional Category, lists the function(s) that an excipient is generally thought to perform, e.g., diluent, emulsi- fying agent, etc.

Section 7, Applications in Pharmaceutical Formulation or Tech- nology, describes the various applications of the excipient.

Section 8, Description, includes details of the physical appear- ance of the excipient, e.g., white or yellow flakes, 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.

Section 10, Typical Properties, describes the physical proper- ties of the excipient which are not shown in Section 9. All 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

Freely soluble 1 part in 1–10

Soluble 1 part in 10–30

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 or insoluble

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

xviii Arrangement

used to generate the data readers should consult the appro- priate previous edition(s) of the Handbook.

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 con- tain the excipient.

Section 12, Incompatibilities, describes the reported incompat- ibilities for the excipient either with other excipients or with 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 pro- duct.

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 method of manufacture.

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 shown.

Section 15, Handling Precautions, indicates possible hazards associated with handling the excipient and makes recommen- dations for suitable containment and protection methods. A 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 guidance.

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 different grades of the excipient available are discussed. Com- ments are the opinion of the listed author(s) unless referenced or indicated otherwise.

Section 19, Specific References, is a list of references cited within the monograph.

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.

Section 21, Authors, lists the current authors of the mono- graph in alphabetical order. Authors of previous versions of the monograph are shown in previous printed editions of the text.

Section 22, Date of Revision, indicates the date on which changes were last made to the text of the monograph.

Acknowledgments

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, concisely, and accurately.

Raymond C Rowe, Paul J Sheskey and Siaˆn C Owen

August 2005

Notice to Readers

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 that excipient or application. Similarly, reports of incompat- ibilities or adverse reactions to an excipient, in a particular application, may not necessarily prevent its use in other applications. Formulators should perform suitable experimen- tal studies to satisfy themselves and regulatory bodies that a 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, Handbook of Pharmaceutical Excipients, American Pharma- cists Association, 2215 Constitution Avenue, NW, Washington, DC 20037-2985, USA.

Bibliography

A selection of publications and websites which contain useful information on pharmaceutical excipients is listed below:

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, 2004.

Bugay DE, Findlay WP. Pharmaceutical Excipients Character- ization by IR, Raman, and NMR Spectroscopy. New York: Marcel Dekker, 1999.

European Pharmacopoeia, 5th edn. and supplements. Stras- bourg: 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 (accessed 11 July 2005).

Food Chemicals Codex, 4th edn. Washington, DC: National Academy Press, 1996.

Health and Safety Executive. EH40/2002: Occupational Exposure Limits 2002. Sudbury: Health and Safety Execu- tive, 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.

Japan Pharmaceutical Excipients Council. Japanese Pharma- ceutical Excipients 2004. Tokyo: Yakuji Nippo, 2004.

Japanese Pharmacopeia, 14th edn. and supplement. Tokyo: Yakuji Nippo, 2001.

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: Pharmaceu- tical 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 Pharmaco- peial Convention, 2005.

University of the Sciences in Philadelphia. Remington: the Science and Practice of Pharmacy, 21st edn. Baltimore: Lippincott Williams and Wilkins, 2005.

Weiner M, Bernstein IL. Adverse Reactions to Drug Formula- tion Agents: a Handbook of Excipients. New York: Marcel Dekker, 1989.

Weiner ML, Kotkoskie LA, eds. Excipient Toxicity and Safety.

New York: Marcel Dekker, 2000.

Abbreviations

Some units, terms, and symbols are not included in this list as they are defined in the text. Common abbreviations have been omitted. The titles of journals are abbreviated according to the general style of the Index Medicus.

≈ approximately.

Ad Addendum.

ADI acceptable daily intake.

approx approximately.

atm atmosphere.

BAN British Approved Name.

bp boiling point.

BP British Pharmacopoeia.

BS British Standard (specification). BSI British Standards Institution. cal calorie(s).

CAS Chemical Abstract Service.

CFC chlorofluorocarbon.

cm centimeter(s).

cm2 square centimeter(s).

cm3 cubic centimeter(s).

cmc critical micelle concentration.

CNS central nervous system.

cP centipoise(s).

cSt centistoke(s).

CTFA Cosmetic, Toiletry, and Fragrance Association.

D&C designation applied in USA to dyes permitted for use in drugs and cosmetics.

DoH Department of Health (UK).

Abbreviations xxi 

DSC differential scanning calorimetry.

EC European Community.

e.g. exemplit gratia, ‘for example’.

EINECS European Inventory of Existing Commercial Chemical Substances.

et al et alii, ‘and others’.

EU European Union.

FAO Food and Agriculture Organization of the United Nations.

FAO/ Food and Agriculture Organization of the United

WHO Nations and the World Health Organization.

FCC Food Chemicals Codex.

FDA Food and Drug Administration of the USA.

FD&C designation applied in USA to dyes permitted for use in foods, drugs, and cosmetics.

FFBE Flat face beveled edge.

g gram(s).

GMP Good Manufacturing Practice.

GRAS generally recognized as safe by the Food and Drug Administration of the USA.

HC hydrocarbon.

HCFC hydrochlorofluorocarbon.

HFC hydrofluorocarbon.

HIV human immunodeficiency virus. HLB hydrophilic–lipophilic balance. HSE Health and Safety Executive (UK).

i.e. id est, ‘that is’.

IM intramuscular.

INN International Nonproprietary Name.

IP intraperitoneal.

ISO International Organization for Standardization.

IU International Units.

intravenous.

joule(s).

JP Japanese Pharmacopeia.

JPE Japanese Pharmaceutical Excipients

kcal kilocalorie(s).

kg kilogram(s).

kJ kilojoule(s).

kPa kilopascal(s).

liter(s).

LAL Limulus amoebocyte lysate.

LC50 a concentration in air lethal to 50% of the specified animals on inhalation.

LD50 a dose lethal to 50% of the specified animals or microorganisms.

LdLo lowest lethal dose for the specified animals or microorganisms.

m meter(s).

m2 square meter(s).

m3 cubic meter(s).

molar.

max maximum.

MCA Medicines Control Agency (UK).



mg milligram(s).

MIC minimum inhibitory concentration.

min minute(s) or minimum.

mL milliliter(s).

mm millimeter(s).

mM millimolar.

mm2 square millimeter(s). mm3 cubic millimeter(s). mmHg millimeter(s) of mercury. mmol millimole(s).

mN millinewton(s).

mol mole(s).

mp melting point.

mPa millipascal(s).

MPa megapascal(s).

mg microgram(s).

mm micrometer(s).

newton(s) or normal (concentration).

nm nanometer(s).

o/w oil-in-water. o/w/o oil-in-water-in-oil. Pa pascal(s).

pH the negative logarithm of the hydrogen ion concentration.

PhEur European Pharmacopeia.

pKa the negative logarithm of the dissociation constant.

pph parts per hundred.

ppm parts per million.

psia pounds per square inch absolute.

RDA recommended dietary allowance (USA).

rpm revolutions per minute.

s second(s).

SC subcutaneous.

SEM scanning electron microscopy or scanning electron microphotograph.

SI Statutory Instrument or SystU¨ me International d’Unites (International System of Units).

TPN total parental nutrition. TWA time weighted average. UK United Kingdom.

US or United States of America.

USA

USAN United States Adopted Name.

USP The United States Pharmacopeia.

USPNF The United States Pharmacopeia National Formulary.

UV ultraviolet.

v/v volume in volume.

v/w volume in weight.

WHO World Health Organization.

w/o water-in-oil.

w/o/w water-in-oil-in-water.

w/v weight in volume.

w/w weight in weight.

Units of Measurement

The information below shows imperial to SI unit conversions for the units of measurement most commonly used in the Handbook. SI units are used throughout with, where appro- priate, imperial units reported in parentheses.

Area

1 square inch (in2) = 6.4516 × 10–4 square meter (m2) 1 square foot (ft2) = 9.29030 × 10–2 square meter (m2)

1 square yard (yd2) = 8.36127 × 10–1 square meter (m2)

Density

1 pound per cubic foot (lb/ft3) = 16.0185 kilograms per cubic meter (kg/m3)

Energy

1 kilocalorie (kcal) = 4.1840 × 103 joules (J)

Force

1 dyne (dynes) = 1 × 10–5 newton (N)

Length

1 angstrom (a˜) = 10–10 meter (m)

1 inch (in) = 2.54 × 10–2 meter (m)

1 foot (ft) = 3.048 × 10–1 meter (m)

1 yard (yd) = 9.144 × 10–1 meter (m)

Pressure

1 atmosphere (atm) = 0.101325 megapascal (MPa)

1 millimeter of mercury (mmHg) = 133.322 pascals (Pa) 1 pound per square inch (psi) = 6894.76 pascals (Pa)

Surface tension

1 dyne per centimeter (dyne/cm) = 1 millinewton per meter (mN/m)

Temperature

Celsius (8C) = (1.8 × 8C) + 32 Fahrenheit (8F) Fahrenheit (8F) = (0.556 × 8F) –17.8 Celsius (8C)

Viscosity (dynamic)

1 centipoise (cP) = 1 millipascal second (mPa s) 1 poise (P) = 0.1 pascal second (Pa s)

Viscosity (kinematic)

1 centistoke (cSt) = 1 square millimeter per second (mm2/s)

Volume

1 cubic inch (in3) = 1.63871 × 10–5 cubic meter (m3) 1 cubic foot (ft3) = 2.83168 × 10–2 cubic meter (m3) 1 cubic yard (yd3) = 7.64555 × 10–1 cubic meter (m3) 1 pint (UK) = 5.68261 × 10–4 cubic meter (m3)

1 pint (US) = 4.73176 × 10–4 cubic meter (m3)

1 gallon (UK) = 4.54609 × 10–3 cubic meter (m3) 1 gallon (US) = 3.78541 × 10–3 cubic meter (m3)

Acacia

Nonproprietary Names

BP: Acacia JP: Acacia

PhEur: Acaciae gummi USPNF: Acacia

Synonyms

Acacia gum; arabic gum; E414; gum acacia; gummi africanum; gum arabic; gummi arabicum; gummi mimosae; talha gum.

Chemical Name and CAS Registry Number

Acacia [9000-01-5]

Empirical Formula and Molecular Weight

Acacia is a complex, loose aggregate of sugars and hemi- celluloses with a molecular weight of approximately 240 000–580 000. The aggregate consists essentially of an arabic acid nucleus to which are connected calcium, mag- nesium, and potassium along with the sugars arabinose, galactose, and rhamnose.

Structural Formula

See Section 4.

Functional Category

Emulsifying agent; stabilizing agent; suspending agent; tablet binder; viscosity-increasing agent.

Applications in Pharmaceutical Formulation or Technology

Acacia is mainly used in oral and topical pharmaceutical formulations as a suspending and emulsifying agent, often in combination with tragacanth. It is also used in the preparation of pastilles and lozenges, and as a tablet binder, although if used incautiously it can produce tablets with a prolonged disin- tegration time. Acacia has also been evaluated as a bioad- hesive;(1) and has been used in novel tablet formulations,(2) and modified release tablets.(3) See Table I.

Acacia is also used in cosmetics, confectionery, food products, and spray-dried flavors.(4)

See also Section 18.

Table I: Uses of acacia.

Use Concentration (%)

Emulsifying agent 10–20

Pastille base 10–30

Suspending agent 5–10

Tablet binder 1–5

Description

Acacia is available as white or yellowish-white thin flakes, spheroidal tears, granules, powder, or spray-dried powder. It is odorless and has a bland taste.

Pharmacopeial Specifications

The PhEur 2005 provides monographs on acacia and spray- dried acacia, while the USPNF 23 describes acacia in a single monograph that encompasses tears, flakes, granules, powder, and spray-dried powder. The JP 2001 also has monographs on acacia and powdered acacia. See Table II.

Table II:  Pharmacopeial specifications for acacia.

 

Test JP 2001 PhEur 2005 USPNF 23    

Identification + + +    

Characters + + +    

Microbial limit — 4104/g +    

Water 417.0%

415.0%(a) 415.0%

410.0%(b) 415.0%

—    

Total ash 44.0% 44.0% 44.0%    

Acid-insoluble ash 40.5% — 40.5%    

Insoluble residue 40.2% 40.5% 450 mg    

Arsenic — — 43 ppm    

Lead — — 40.001%    

Heavy metals — — 40.004%    

Starch, dextrin, and agar + + +    

Tannin-bearing gums + + +    

Tragacanth — + —    

Sterculia gum — + —    

Glucose and fructose — + —    

Solubility and reaction — — +    

Organic volatile impurities — — +    

(a) Powdered acacia.    

(b) Spray-dried acacia.  

Typical Properties

Acidity/alkalinity: pH = 4.5–5.0 (5% w/v aqueous solution)

Acid value: 2.5

Hygroscopicity: at relative humidities of 25–65%, the equili- brium moisture content of powdered acacia at 258C is 8–13% w/w, but at relative humidities above about 70% it absorbs substantial amounts of water.

Solubility: soluble 1 in 20 of glycerin, 1 in 20 of propylene glycol, 1 in 2.7 of water; practically insoluble in ethanol (95%). In water, acacia dissolves very slowly, although almost completely after two hours, in twice the mass of water leaving only a very small residue of powder. The solution is colorless or yellowish, viscous, adhesive, and translucent. Spray-dried acacia dissolves more rapidly, in about 20 minutes.

Specific gravity: 1.35–1.49

Viscosity (dynamic): 100 mPa s (100 cP) for a 30% w/v aqueous solution at 208C. The viscosity of aqueous acacia solutions varies depending upon the source of the material, processing,

2 Acacia

storage conditions, pH, and the presence of salts. Viscosity increases slowly up to about 25% w/v concentration and exhibits Newtonian behavior. Above this concentration, viscosity increases rapidly (non-Newtonian rheology). Increasing temperature or prolonged heating of solutions results in a decrease of viscosity owing to depolymerization or particle agglomeration. See also Section 12.

Stability and Storage Conditions

Aqueous solutions are subject to bacterial or enzymatic degradation but may be preserved by initially boiling the solution for a short time to inactivate any enzymes present; microwave irradiation can also be used.(5) Aqueous solutions may also be preserved by the addition of an antimicrobial preservative such as 0.1% w/v benzoic acid, 0.1% w/v sodium benzoate, or a mixture of 0.17% w/v methylparaben and 0.03% propylparaben. Powdered acacia should be stored in an airtight container in a cool, dry place.

Incompatibilities

Acacia is incompatible with a number of substances including amidopyrine, apomorphine, cresol, ethanol (95%), ferric salts, morphine, phenol, physostigmine, tannins, thymol, and vanil- lin.

An oxidizing enzyme present in acacia may affect prepara- tions containing easily oxidizable substances. However, the enzyme may be inactivated by heating at 1008C for a short time; see Section 11.

Many salts reduce the viscosity of aqueous acacia solutions, while trivalent salts may initiate coagulation. Aqueous solu- tions carry a negative charge and will form coacervates with gelatin and other substances. In the preparation of emulsions, solutions of acacia are incompatible with soaps.

Method of Manufacture

Acacia is the dried gummy exudate obtained from the stems and branches of Acacia senegal (Linne´) Willdenow or other related species of Acacia (Fam. Leguminosae) that grow mainly in the Sudan and Senegal regions of Africa.

The bark of the tree is incised and the exudate allowed to dry on the bark. The dried exudate is then collected, processed to remove bark, sand, and other particulate matter, and graded. Various acacia grades differing in particle size and other physical properties are thus obtained. A spray-dried powder is also commercially available.

Safety

Acacia is used in cosmetics, foods, and oral and topical pharmaceutical formulations. Although it is generally regarded as an essentially nontoxic material, there have been a limited number of reports of hypersensitivity to acacia after inhalation or ingestion.(6,7) Severe anaphylactic reactions have occurred following the parenteral administration of acacia and it is now no longer used for this purpose.(6)

The WHO has not set an acceptable daily intake for acacia as a food additive because the levels necessary to achieve a desired effect were not considered to represent a hazard to health.(8)

LD50 (hamster, oral): >18 g/kg(9) LD50 (mouse, oral): >16 g/kg LD50 (rabbit, oral): 8.0 g/kg

LD50 (rat, oral): >16 g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Acacia can be irritant to the eyes and skin and upon inhalation. Gloves, eye protection, and a dust respirator are recommended.

Regulatory Status

GRAS listed. Accepted for use in Europe as a food additive. Included in the FDA Inactive Ingredients Guide (oral prepara- tions and buccal or sublingual tablets). Included in the Canadian List of Acceptable Non-medicinal Ingredients. Included in nonparenteral medicines licensed in the UK.

Related Substances

Ceratonia; guar gum; tragacanth.