Handbook of pharmaceutical excipients: 6th Revised edition

Product Information

Compounds which swell or dissolve in water e.g. starch, cellulose derivatives and alginates, crospovidone Acesulfame potassium occurs as a colorless to white-colored, odorless, crystalline powder with an intensely sweet taste. 9 hamster, oral): 6.1 g/kg(10) (mouse, oral): 16.0 g/kg (rabbit, oral): 5.8 g/kg (rat, oral): 11.0 g/kg

Acesulfame potassium possesses good stability. In the bulk form it shows no sign of decomposition at ambient temperature over many years. In aqueous solutions (pH 3.0–3.5 at 208C) no reduction in sweetness was observed over a period of approximately 2 years. Stability at elevated temperatures is good, although some decomposition was noted following storage at 408C for several months. Sterilization and pasteurization do not affect the taste of acesulfame potassium.(5) The bulk material should be stored in a well-closed container in a cool, dry place. 12Acetyltributyl citrate is used to plasticize polymers in formulated pharmaceutical coatings,(1–5) including capsules, tablets, beads, and granules for taste masking, immediate release, sustained-release and enteric formulations. Characters Identification Appearance of solution Acidity or alkalinity Acetylacetamide Impurity B and related substances Fluorides Heavy metals Loss on drying Assay Human serum albumin has a molecular weight of about 66 500 and is a single polypeptide chain consisting of 585 amino acids. Characteristic features are a single tryptophan residue, a relatively low content of methionine (6 residues), and a large number of cysteine (17) and of charged amino acid residues of aspartic acid (36), glutamic acid (61), lysine (59), and arginine (23). 5

Steurnagel CR. Latex emulsions for controlled drug delivery. In: McGinity JW, ed. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms. New York: Marcel Dekker, 1989: 1–61. 4 Gutierrez-Rocca JC, McGinity JW. Influence of aging on the physical-mechanical properties of acrylic resin films cast from aqueous dispersions and organic solutions. Drug Dev Ind Pharm 1993; 19(3): 315–332. 5 Repka MA, Gerding TG, Repka SL. Influence of plasticisers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion. Drug Dev Ind Pharm 1999; 25(5): 625–633. 6 Lieb S, Szeimies RM, Lee G. Self-adhesive thin films for topical delivery of 5-aminolevulinic acid. Eur J Pharm Biopharm 2002; 53(1): 99–106. 7 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 3512. 8 Goulas AE, Riganakos KA, Ehlermann DA, et al. Effect of highdose electron beam irradiation on the migration of DOA and ATBC plasticizers from food-grade PVC and PVDC/PVC films, respectively, into olive oil. J Food Prot 1998; 61(6): 720–724. 9 Dorfer CE, Kim TS, Steinbrenner H, et al. Regenerative periodontal surgery in interproximal intrabony defects with biodegradable barriers. J Clin Peridontol 2000; 27(3): 162–168.Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection, gloves, and a dust mask are recommended. 16

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 Pharmaceutics 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 Pharmaceutical Excipients as an author and member of the Steering Pharmaceutical dosage forms contain both pharmacologically active compounds and excipients added to aid the formulation and manufacture of the subsequent dosage form for administration 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 developed 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 CDROM, 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 haveObserve normal precautions appropriate to the circumstances and quantity of the material handled. When heated to decomposition, agar emits acrid smoke and fumes. 16 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 International Scope: Recognized globally as the authority on the uses, properties and safety of excipients Agar is widely used in food applications and has been used in oral and topical pharmaceutical applications. It is generally regarded as relatively nontoxic and nonirritant when used as an excipient. LD50 LD50 LD50 LD50 15

Boiling point: 56.28C Flash point: –208C Melting point: 94.38C Refractive index: n20 D = 1.359 Solubility: soluble in water; freely soluble in ethanol (95%) Vapor pressure: 185 mmHg at 208C 11 Section 17, Related Substances, lists excipients similar to the excipient discussed in the monograph. GRAS listed. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Guide (injections, nasal, ophthalmic, and oral preparations). Included in parenteral and nonparenteral preparations licensed in the UK. 17 Bonding index: 0.007 Brittle fracture index: 0.08(3) Flowability: 19% (Carr compressibility index)(3) Density (bulk): 1.04 g/cm3(3) Density (tapped): 1.28 g/cm3(3) Elastic modulus: 4000 MPa(3) Melting point: 2508C Solubility: see Table II. Specific volume: 0.538 cm3/g(4) Tensile strength: 0.5 MPa(3) Viscoelastic index: 2.6(3) Acetyltriethyl citrate is used to plasticize polymers in formulated pharmaceutical coatings.(1) The coating applications include capsules, tablets, beads and granules for taste masking, immediate release, sustained-release and enteric formulations.(2–5) It is also used in diffusion-controlled release drug delivery systems.(6)

Handbook of Pharmaceutical Excipients

Acetyltriethyl citrate is used in oral pharmaceutical formulations and is generally regarded as a nontoxic and nonirritating material. However, ingestion of large quantities may be harmful. LD50 (cat, oral): 8.5 g/kg(7) LD50 (mouse, IP): 1.15 g/kg LD50 (rat, oral): 7 g/kg 15 Acacia is a complex, loose aggregate of sugars and hemicelluloses with a molecular weight of approximately 240 000–580 000. The aggregate consists essentially of an arabic acid nucleus to which are connected calcium, magnesium, and potassium along with the sugars arabinose, galactose, and rhamnose. 5 The Handbook of Pharmaceutical Excipients is internationally recognized as the world’s most authoritative source of information on pharmaceutical excipients. It is the definitive comprehensive guide to uses, properties and safety of excipients providing scientists and researchers with a one stop resource when researching an excipient.