Contributors xi 

NA Hodges University of Brighton Brighton, UK

JT Irwin

Perrigo Corporation MI, USA

BR Jasti

University of the Pacific Stockton, CA, USA

R Johnson AstraZeneca Loughborough, UK

DS Jones

The Queen’s University of Belfast Belfast, UK

AS Kearney

GlaxoSmithKline

King-of-Prussia, PA, USA

SW Kennedy

Morflex Inc Greensboro, NC, USA

VL Kett

The Queen’s University of Belfast Belfast, UK

AH Kibbe

Wilkes University Wilkes-Barre, PA, USA

V King

Rhodia Inc Cranbury, NJ, USA

PB Klepak

Reheis Inc

Berkley Heights, NJ, USA

JJ Koleng

University of Texas at Austin Austin, TX, USA

K Kussendrager

DMV International Veghel, The Netherlands

WJ Lambert

Eisai Inc

Research Triangle Park, NC, USA

BA Langdon Pfizer Inc Groton, CT, USA

MJ Lawrence

King’s College, University of London London, UK

JC Lee

Cellegy

San Jose´, CA, USA



MG Lee

Medicines and Healthcare products Regulatory Agency

London, UK

X Li

University of the Pacific Stockton, CA, USA

EB Lindblad

Brenntag Biosector Frederikssund, Denmark

O Luhn

Palatinit GmbH Mannheim, Germany

PE Luner

Pfizer Inc Groton, CT, USA

HJ Mawhinney

The Queen’s University of Belfast Belfast, UK

CP McCoy

The Queen’s University of Belfast Belfast, UK

OS McGarvey

The Queen’s University of Belfast Belfast, UK

JW McGinity

University of Texas at Austin Austin, TX, USA

LME McIndoe

Royal Pharmaceutical Society of Great Britain

London, UK

LA Miller

Pfizer Inc Groton, CT, USA

RW Miller

Bristol-Myers Squibb New Brunswick, NJ, USA

J-P Mittwollen

BASF Aktiengesellschaft Ludwigshafen, Germany

RC Moreton

Idenix Pharmaceuticals Cambridge, MA, USA

G Mosher CyDex Inc Lenexa, KS, USA

C Mroz

Colorcon Ltd Dartford, Kent, UK



MP Mullarney Pfizer Inc Groton, CT, USA

S Murdande Pfizer Inc Groton, CT, USA

RA Nash

St John’s University Jamaica, NY, USA

S Nema

Pfizer Inc

Chesterfield, MO, USA

SC Owen

Royal Pharmaceutical Society of Great Britain

London, UK

A Palmieri University of Florida Gainesville, FL, USA

D Parsons ConvaTec Ltd Clwyd, UK

Y Peng

University of Tennessee Memphis, TN, USA

JD Pipkin CyDex Inc Lenexa, KS, USA

D Pipkorn

Pfizer Inc

Ann Arbor, MI, USA

JC Price

University of Georgia Athens, GA, USA

MA Repka

University of Mississippi University, MS, USA

B Sarsfield

Bristol-Myers Squibb New Brunswick, NJ, USA

T Schmeller

BASF Aktiengesellschaft Ludwigshafen, Germany

A Schoch

Palatinit GmbH Mannheim, Germany

CJ Sciarra

Sciarra Laboratories Inc Hicksville, NY, USA

xii Contributors

Sciarra

Sciarra Laboratories Inc Hicksville, NY, USA

SA Shah

Watson Pharmaceuticals Corona, CA, USA

RM Shanker Pfizer Inc Groton, CT, USA

PJ Sheskey

The Dow Chemical Co Midland, MI, USA

AJ Shukla

University of Tennessee Memphis, TN, USA

Singh

SNDT Women’s University Mumbai, India

R Steer AstraZeneca Loughborough, UK

JT Stewart

University of Georgia Athens, GA, USA

Y Sun

University of Tennessee Memphis, TN, USA

AK Taylor

Baton Rouge, LA, USA

MS Tesconi

Wyeth Research Pearl River, NY, USA

D Thassu

UCB Pharma Inc Rochester, NY, USA

BF Truitt

Pfizer Inc Groton, CT, USA

CK Tye

Pfizer Inc Kalamazoo, MI, USA

HM Unvala

Bayer Corporation Myerstown, PA, USA

KD Vaughan

Boots Healthcare International Nottingham, UK

H Wang

Pfizer Inc Groton, CT, USA

PJ Weller

Royal Pharmaceutical Society of Great Britain

London, UK

AJ Winfield

Aberdeen, UK

AW Wood

GlaxoSmithKline

Research Triangle Park, NC, USA

M Yelvigi

Wyeth Research Pearl River, NY, USA

PM Young University of Sydney Sydney, Australia

About the Editors

Raymond C Rowe

BPharm, PhD, DSc, FRPharmS, CChem, FRSC, CPhys, MInstP

Raymond Rowe has been involved in the Handbook of Pharmaceutical Excipients since the first edition was published in 1986, initially as an author then as a Steering Committee member. In addition to his position as Chief Scientist at Intelligensys, UK, he is also Professor of Industrial Pharmaceu- tics at the School of Pharmacy, University of Bradford, UK. He was formerly Senior Principal Scientist at AstraZeneca, UK. In 1998 he was awarded the Chiroscience Industrial Achievement Award, and in 1999 he was the British Pharmaceutical Conference Science Chairman. He has contributed to over 350 publications in the pharmaceutical sciences including a book and eight patents.

Paul J Sheskey

BSc, RPh

Paul Sheskey has been involved in the Handbook of Pharma- ceutical Excipients as an author and member of the Steering

Committee since the third edition. He is a Technical Service Leader in the Water Soluble Polymers, Pharmaceutical R&D Group at The Dow Chemical Company in Midland, Michigan, USA. Paul received his BSc degree in pharmacy from Ferris State University. Previously, he has worked as a research pharmacist in the area of solid dosage form development at the Perrigo Company and the Upjohn (Pharmacia) Company. Paul has authored numerous journal articles in the area of pharmaceutical technology. He is a member of the AAPS, Controlled Release Society, and the Institute for Briquetting and Agglomeration.

Siaˆn C Owen

BSc, MA

Siaˆn Owen has been involved with the Handbook of Pharmaceutical Excipients since the fourth edition, as a contributor and Steering Committee member. Siaˆn received her BSc degree in pharmacology from the University of Sunderland, and her MA in biotechnological law and ethics from the University of Sheffield.

New Monographs

The following new monographs have been added to the Handbook of Pharmaceutical Excipients, 5th edition.

Acetone Agar

Aluminum Hydroxide Adjuvant Aluminum Oxide

Aluminum Phosphate Adjuvant Ammonium Alginate Aluminum Stearate

Boric Acid Calcium Alginate

Cetylpyridinium Chloride Copovidone Dimethylacetamide Disodium Edetate Erythorbic Acid Erythritol

Ethyl Lactate

Ethylene Vinyl Acetate Hectorite Hydroxypropyl Starch

Hypromellose Acetate Succinate Inulin

Iron Oxides Isomalt

Lactose, Anhydrous Lactose, Monohydrate Lactose, Spray-Dried

Lauric Acid Leucine Linoleic Acid

Macrogol 15 Hydroxystearate Myristic Acid

Neohesperidin Dihydrochalcone Octyldodecanol

Oleyl Alcohol Palmitic Acid Pectin Polycarbophil

Poly(methylvinyl ether/maleic anhydride) Potassium Alginate

2-Pyrrolidone Raffinose Saponite Sodium Acetate Sodium Borate

Sodium Hyaluronate Sodium Lactate Sodium Sulfite

Sulfobutylether b-Cyclodextrin Thaumatin

Thymol Zinc Acetate

Related Substances

Acetic acid Activated attapulgite Aleuritic acid

d-Alpha tocopherol

d-Alpha tocopheryl acetate

dl-Alpha tocopheryl acetate

d-Alpha tocopheryl acid succinate dl-Alpha tocopheryl acid succinate Aluminum distearate

Aluminum monostearate Amylopectin

a-Amylose Anhydrous citric acid

Anhydrous sodium citrate Anhydrous sodium propionate Artificial vinegar

Bacteriostatic water for injection Bentonite magma

Beta tocopherol Beta-carotene

n-Butyl lactate Butylparaben sodium Calcium ascorbate Calcium cyclamate Calcium polycarbophil Calcium propionate Calcium silicate Calcium sorbate

Calcium sulfate hemihydrate Capric acid

Carbon dioxide-free water Cationic emulsifying wax Ceratonia extract Cetylpyridinium bromide Chlorhexidine acetate Chlorhexidine gluconate Chlorhexidine hydrochloride Chlorodifluoromethane Chlorophenoxyethanol

Corn syrup solids

m-Cresol o-Cresol p-Cresol

Crude olive-pomace oil Cyclamic acid

De-aerated water Dehydrated alcohol Delta tocopherol Denatured alcohol Dextrose anhydrous Diazolidinyl urea

Dibasic potassium phosphate Diethylene glycol monopalmitostearate Dilute acetic acid

Dilute alcohol

Dilute ammonia solution Dilute hydrochloric acid Dilute phosphoric acid Dilute sulfuric acid Dimethyl-b-cyclodextrin Dioctyl phthalate Dipotassium edetate Docusate calcium Docusate potassium Dodecyl gallate

Dodecyltrimethylammonium bromide Edetate calcium disodium

Eglumine Ethyl gallate

Ethylene glycol monopalmitate Ethylene glycol monostearate Ethyl linoleate

Ethylparaben potassium Ethylparaben sodium Extra virgin olive oil Fine virgin olive oil Fuming sulfuric acid Gamma tocopherol Hard water

Hesperidin Hexadecyltrimethylammonium bromide High-fructose syrup

Hyaluronic acid Hydrogenated lanolin

Hydrogenated vegetable oil, type II 2-Hydroxyethyl-b-cyclodextrin

2-Hydroxypropyl-b-cyclodextrin 3-Hydroxypropyl-b-cyclodextrin Indigo carmine

Invert sugar Isotrehalose

Lampante virgin olive oil Lanolin alcohols ointment DL-Leucine

Liquefied phenol Liquid fructose

Magnesium carbonate anhydrous Magnesium carbonate hydroxide Magnesium lauryl sulfate Magnesium metasilicate Magnesium orthosilicate Magnesium trisilicate anhydrous D-Malic acid

L-Malic acid

Menthol l-Menthol

Methyl lactate Methyl linoleate Methyl methacrylate Methyl oleate

Related Substances xv 

Methylparaben potassium Methylparaben sodium

N-Methylpyrrolidone

Microcrystalline cellulose and carboxymethylcellulose sodium Microcrystalline cellulose and carrageenan

Microcrystalline cellulose and guar gum Modified lanolin

Monobasic potassium phosphate Montmorillonite

Myristyl alcohol Neotrehalose

Normal magnesium carbonate Octyl gallate

Oleyl oleate Olive-pomace oil Palmitin

Pharmaceutical glaze Phenoxypropanol Polacrilin

Poly(methyl methacrylate) Potassium bisulfite Potassium myristate Potassium propionate Powdered fructose Propan-1-ol

(S)-Propylene carbonate Propylparaben potassium Propylparaben sodium Purified bentonite Purified stearic acid Quaternium 18-hectorite Rapeseed oil

Refined almond oil Refined olive-pomace oil



Saccharin ammonium Saccharin calcium

Self-emulsifying glyceryl monostearate Shellolic acid

Sodium bisulfite

Sodium borate anhydrous Sodium edetate

Sodium erythorbate Sodium laurate Sodium myristate Sodium palmitate Sodium sorbate

Sodium sulfite heptahydrate Soft water

Sorbitol solution 70% Spermaceti wax Stearalkonium hectorite Sterile water for inhalation Sterile water for injection Sterile water for irrigation Sunset yellow FCF Synthetic paraffin

DL-( )-Tartaric acid Tartrazine Theobroma oil Tocopherols excipient

Tribasic sodium phosphate Trimethyl-b-cyclodextrin

Trimethyltetradecylammonium bromide Trisodium edetate

Virgin olive oil Water for injection White petrolatum Zinc propionate

Preface

Pharmaceutical dosage forms contain both pharmacologically active compounds and excipients added to aid the formulation and manufacture of the subsequent dosage form for adminis- tration to patients. Indeed, the properties of the final dosage 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 excipients being used and suppliers of excipients have devel- oped novel excipient mixtures and new physical forms to 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 2004 online. This new printed edition with its companion CD- ROM, Pharmaceutical Excipients 5, contains 300 monographs 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