Der Pharmazeutische Betrieb

Fiedler - Encyclopedia of Excipients / Buch

vonEva-Marie Hoepfner, Siegfried Lang, Alwin Reng, Peter Christian Schmidt

Neuausgabe

Fiedler - Encyclopedia of Excipients / Buch – Hoepfner / Lang / Reng / et al.

schnell und portofrei erhältlich bei beck-shop.de DIE FACHBUCHHANDLUNG

Thematische Gliederung:

Pharmakologie, Toxikologie – Pharmakologie, Toxikologie

ECV Editio Cantor 2007

Verlag C.H. Beck im Internet:www.beck.de

ISBN 978 3 87193 346 2

Inhaltsverzeichnis: Fiedler - Encyclopedia of Excipients / Buch – Hoepfner / Lang / Reng / et al.

341

Properties White powder or granulate, content of sodiumCMC calculated on bone dry basis > 99.5 %, pH of 1 %solution 6.5–8.0, decomposition temperature approx.240°.Applications For pharmaceutical formulations and cos-metic products like toothpaste.Toxicology LD50 (rat, oral) > 27 000 mg/kg, non irritant,non mutagenic, non carcinogenic.

(Celanese)Definition Trade name for various hydroxyethylcelluloseproducts, water-soluble hydrocolloids.Applications For the manufacture of gelatinous productsor viscous solutions.

(Celanese)Definition Trade name for 3 different kinds of water-sol-uble hydroxyethyl methyl cellulose with different degreesof viscosity, which contain about 2 % bound hydroxyeth-yl groups in addition to the methoxy groups.Properties Available as powder, fibrous material orgranules (HEM 1000 only as fiber). The moisture contentis approx. 8–10 %. HEM 450, viscosity (all of the follow-ing data refer to 2 % aqueous solutions) 350–550 cP,HEM 1000, viscosity 850–1150 cP, HEM 2500, viscosity2200–2800 cP. All C. HEM types are characterized by ahigher tolerance to salt than the corresponding Celacolmethylcellulose types and are also more hydrophilic.Applications They are recommended as suspending,thickening and stabilizing agents etc.

(Celanese)Definition Trade name for hydroxypropyl methylcellu-lose.

(Celanese)Definition Trade name for methylcellulose products,which yield solutions of varying viscosity and are suit-able as “special“ types for the manufacture of foods orpharmaceutical preparations.Properties Moisture content 8–10 %, content of arsenic< 1.0 ppm, copper < 15.5 ppm, lead < 5.0 ppm, zinc < 50ppm, free from dimethyl sulfate. The following types areoffered: M. 20, powder or fibers, viscosity (all of the fol-lowing values apply to 2 % aqueous solutions) 15–25 cP,M. 100, powder or fibers, viscosity 85–115 cP, M. 450,powder, fibers or granules, viscosity 350–550 cP, M.1000, powder or fibers, viscosity 850–1150 cP, M. 2500,powder, fibers or granules, viscosity 2200–2800 cP, MM.10, fibers, viscosity 9–11 cP, MM. 100, fibers, viscosity85–115 cP, MM. 1000, powder or fibers, viscosity 850–1150 cP.Applications C. M. 450 is primarily suitable as a tabletbinder (0.5–2.0 %), for the manufacture of mucilagepreparations, laxatives etc. The other types are used forthe manufacture of a wide range of suspensions, of O/Wemulsions (2–3 %), capsules, ointments (M. 2500 or M.1000), oil-containing creams or lotions (M. 100 or M.

Celacol HE

Celacol HEM

Celacol HPM

Celacol methylcellulose

450, 2–5 %), eye and ear drops, contact lense solutions (a1 % M. 2500 solution has the same nD as the eye mu-cosa), of antacid preparations etc.

(Celanese)Definition A hydroxypropyl methylcellulose with a molwt of approx. 100 000.Properties Giving highly viscous solutions even at lowconcentrations, resulting in a non sticky film on the skin.

(Johns Manville)Definition CAS 61790-53-2, Kieselgur, filter aid. Thefollowing types are available: C. 500, 512, 545 and 560(H. Kranich and R. J. Zilli, Soap Chem. Specialties 42,(12), 73 [1966]).

(Meggle)Definition Trade name for a spray-dried compound of 75% α-lactose monohydrate (Ph Eur, USP/NF, JP) and 25% cellulose powder (Ph Eur). See SEM picture.

Properties A white, odorless powder, partly soluble inwater. High compactability, high dilution and adherencepotential.Product data Assay: lactose 73.0–77.0 %, cellulosepowder 23.0–27.0 %, pH-value 4.0–7.0, loss on dryingmax. 3.5 %, water 4.0–7.0 %, residue on ignition max.0.2 %, heavy metals max. 5 ppm, OVIs conform. Micro-biological status: aerobic count max. 11/g, yeasts andmoulds max. 10/g, E. coli negative/10 g, S. ssp. negative/10 g. Particle size distribution: < 32 µm max. 20 %, < 160µm 35–65 %, < 250 µm min. 80 %. Angle of repose 32–35°, bulk density 0.38 g/ml, tapped density 0.47 g/ml,Hausner ratio 1.24.Applications Direct compression aid for high dosageforms, especially cores for coating.

(ICI)Definition Sodium carboxymethylcellulose, nonionicthickener ( cellulose gum).

Celacol Powder DS

Celite

Cellactose 80

Cellofas B

Cel

404

frequently stated opinion that C. or other fish oils are suit-able for preventing arteriosclerosis has not been suffi-ciently demonstrated according to G. Schlierf (Dtsch.med. Wschr. 112, 701 [1987]). According to studies byAl-Meshal et al. performed in rats, C. is able to preventthe inhibition of mucous secretion by the gastric mucosainduced by indomethacin (Life Sci. 48, 1401 [1991];Toxicol. Abstr. 14, No. 8-4902 [1991]).Toxicology C. may contain toxaphene, also called cam-phechlor. Toxaphene (approx. C19H10Cl8, mol wt approx.414, mp 65–95°, LD50 (rat, oral) 80 mg/kg) is a chlorinat-ed camphene which is used as an insecticide. It has beenagreed that the T. content of C. shall be ≤ 0.4 mg/kg(Pharm. Ztg. 136, 2215 [1991]).Analytics HPLC method for the determination of vitaminD3 in medicinal C. (D. Ropte and M. Neumann, Zbl.Pharm. 124, 331 [1985]).

Definition INCI Ethyl Morrhuate, CAS 73049-58-8.

Definition Non-dairy creamers.Applications Substitutes for coffee cream that are manu-factured from vegetable fats and are very fashionable inthe USA (cf. Norda Schimmel Briefs No. 440, April1972); some formulations for manufacturing C. are givenin this brief.

(Cosmetochem)Definition Trade name for a base for hair setting lotions,a mixture of partially quaternized mixed vinyl resin poly-mers and hydantoin resins. Solid content approx. 24 %.Applications As a resin base or as an additive to hair set-ting lotions for achieving particularly adhesive clear andcolored hair setting lotions. Different forms of C. areavailable (dissolved in isopropyl alcohol-water or only inwater). Concentration 5–10 %.

(Cosmetochem)Definition Trade name for a hairspray additive for weath-erproof hairsprays. A combination of a mixed vinyl resinpolymer containing hydroxybenzophenone together withwool wax fractions, cholesterol and silicones. Solids ap-prox. 25 %. C. is offered in various solution systems.Applications C. is intended to be used as an additive tohairsprays in order to reduce the moisture sensitivity ofhair and to increase its elasticity. C. is also a coatingwhich protects from UV light. Concentration 0.5–0.6 %(related to the finished product).

Definition Synonym for ethanolamine.

Definition C. is the European Trade Association repre-senting the interests of the cosmetic, toiletry and perfum-ery industry. C. membership consists of 22 national asso-ciations out of 25 EU member states and 26 internationalcompanies. C. represents more than 2000 companies and

Cod liver oil fatty acid ethyl ester

Coffee whiteners

Co-Fix

Co-Flex

Colamine

COLIPA

the industry employs over 500,000 people within the Eu-ropean Union. www.colipa.org.References Guidelines for the Evaluation of the Efficacyof Cosmetic Products, 2nd Edition, COLIPA (The Euro-pean Cosmetic Toiletry and Perfumery Association),2001.

Definition Isinglass

(Gelita, Pentapharm)Definition Ossein, a scleroprotein, a simple fibrillar pro-tein substance, CAS 9007-34-5, mol wt 130 000.Properties Scleroproteins are intercellular main constitu-ents of mesenchymal support substances. The scleropro-teins include C. (which occurs in connective tissue, intendons, ligaments, bone, cartilage and skin), elastin (ten-dons, elastic fibers, blood vessels, connective tissues),keratins (hair, nails, skin), silk fibroin (cocoon filamentsof the silkworm moth) and skeletines (halogen-containingscleroproteins, skeletal substance of invertebrate ani-mals). C. dissolves in water upon prolonged heating andforms a colloidal soluble glue, which solidifies on cool-ing. The gelatin thus obtained can be enzymaticallycleaved. Properties (P. Morganti et al., J. Appl. Cosmetol.4, No. 4, 141 [1986] [it]; C. A. 107, 140861 [1987]) and(T. Miyata, Fragrance J. 17, 90, 109 [1989] [jap]; C. A.111, 59908 and 09 [1989]).Product data Pentapharm offers C. with the followingproduct data: a viscous, slightly opalescant, colorless toslightly yellow colored solution containing 1 % C. in cit-rate buffer pH 3.4–3.8, with 0.15 % benzoic acid as a pre-servative;, dry residue 3.1–3.6 %, chloride content max.0.4 %, total nitrogen 0.16–0.20 %, hydroxyproline con-tent 0.12–0.15 %, C. content 0.9–1.1 %, sodium benzoate0.15–0.20 %.Applications Biological properties are attributed to C.hydrolysates obtained by special procedures (R. Riemen-schneider and W. H. Chik, Cosmet. Toiletries 94, No. 5,61 [1979]; Textilbericht 62, No. 22, 67–68 [1978]). C.hydrolysates are claimed to have skin care properties. Ac-cording to various studies this is primarily due to the factthat C. improves the water retention capacity of the stra-tum corneum. E. E. Sabelmann gave a review of the biol-ogy, biotechnology and biocompatibility of C. (246 refer-ences) (Biocompat. Tissue Analogs 1, 27 [1985]; C. A.103, 220658 [1985]). M. D. Bucevschi et al. describe themanufacture of C. derivatives esterified with low molecu-lar weight aliphatic alcohols (Rom. RO 82.037 of 15. 4.81/30. 6. 83; C. A. 101, 213039 [1984]). P. H. Cade pub-lished a survey of various C. derivatives (HAPPI, House-hold Pers. Prod. Ind. 21, No. 9, 50 [1984]; C. A. 101,197906 [1984]). Dilute C. can form inactive complexeswith active substances (Farmatsiya [Moscow] 33, No. 6,17 [1984]; C. A. 102, 84335 [1985]). Manufacturing pro-cedures for C. (M. D. Ranganayaki et al., Res. Ind. 33,205 [1988]; C. A. 110, 101502 [1989]), M. Hata (Japan.Kokai Tokkyo Koho JP 03 11.100 of 6. 6. 89/18. 1. 91; C.A. 114, 214169 [1991]) and R. Armengol (SÖFW 117,717 [1991]); procedure for extracting acetylated C. (Y.Suzuki, Japan Kokai Tokkyo Koho JP 02 62.815 of 30. 8.88/2. 3. 90; C. A. 113, 120623 [1990]). R.-D. Petersenrightly states that C.s are not only auxiliary substances

Colla piscium

Collagen

Cod

405

but are also bioactive (Apoth.-J. 1990, No. 1, 6). N. Skal-ko and M. Cajkovac discuss the range of application of C.(Farm. Glas. 45, 1 [1989] [ser]; I. P. A. 26, 12505[1989]), T. Miyata (Fragrance J. 18, No. 3, 70 [1990][jap]; C. A. 113, 217734 [1990]), T. Miyata (Fragrance J.18, No. 3, 180 [1990] [jap]; C. A. 112, 185531 [1990]),E. S. Lower (Parfüm Kosmet. 72, 465 [1991]), J. Cotteand H. Dumas (J. Pharm. Belg. 46, 201 [1991]; C. A.115, 119792 [1991]) and M. Chvapil and B. J. Snider(Report 1990, Order-Nr. AD-219945, 81 pp; Avail. NTISFrom Gov. Report Announce Index [U.S.] 1990, 90 [14]para no. 037027; C. A. 114, 179904 [1991]) (manufactureof skin protective films). Compound delivery using rapid-ly dissolving C. films (WO 99/61047; Pharm. Ind. 62,368 [2000]).Nano particles that are suitable for microencapsulation ofdrugs can be manufactured from C. (J. Pharm. Pharma-col. 35, 537 [1983]; I. P. A. 21, 8280 [1984]). Accordingto F. A. Kinci et al. C. is also suited as a drug carrier, e. g.for tetracycline (Arch. Pharm. 317, 657 [1984]; I. P. A.22, 3937 [1985]; C. A. 101, 136972 [1984]), L. P. Istra-nov et al. (Farmatsiya [Moscow] 33, No. 5, 76 [1984][rus]; C. A. 102, 31963 [1985]). C. as a biomaterial fordrug delivery (W. Friess, Eur J. Pharm. A. Biopharm. 45,113 [1998]; I. P. A. 36, 3605724 [1999]). By cross-link-ing of purified C. with a glycosaminoglycan (chon-droitin-6-sulfate) films are obtained which can be used as‘artificial skin’ (I. V. Yannas et al., Polymer. Mater. Sci.Eng. 57, 28 [1987]; C. A. 107, 205126 [1987]). Accord-ing to S. D. Coapman et al. permeation of C. can be testedin vitro in hairless mouse skin (J. Soc. Cosmet. Chemists39, No. 5, 275 [1988]; C. A. 110, 82267 [1989]). Accord-ing to J. Petres deficiencies of the soft parts of the skin incertain places can be corrected by injecting C. (Kosmetikinternational 1990, No. 4, 117). The design and applica-tions of a liposomal system for age defying skin careproducts that modulates epidermal cytokine production toselectively increase C. III, including in vitro and in vivostudies, are described (R. K. Chaudhuri et al., Cosmet.Toiletries 115, 53 [2000], I. P. A. 38, 3801297 [2001]).T. Miyata reports on application of C. and steloc (ShinTanpakushhitsu Oyo Kagaku 679 [1996] [jap]; C. A. 128,16309 [1998]). On medical application of C. (J. Guan andJ. Wu, Junshi Yixue Kexueyuan Yuankan 21, 4, 305[1997] [ch]; C. A. 128, 299396 [1998]). C. sponges andits hemostatic properties (J. Wu et al., Shengwu YixueGongchengxue Zashi 15, 1, 63 [1998], C. A. 129, 72177[1998]). Structural analysis of C. sponge and its biologi-cal evaluation (J. Wu et al., Junshi Yixue KezueyuanYuankan 22, 281 [1998]; C. A. 133, 9538 [1999]). S.Trasciatti et al. report on in vitro effects of different for-mulations of bovine C. on cultured human skin (Biomate-rials 19, 10, 897 [1998]; C. A. 129, 140598 [1998]). Theeffect of C. implant materials on wound healing (G. E.Romanos et al., Biol. Matrices Tissue Reconstr. 13[1998]; C. A. 129, 293794 [1999]). The roles of keratinand C. in skin keratinization mechanisms (16 refs) (Y.Kitajima, Kobunshi 47, 746 [1998]; C. A. 130, 56947[1999]).If C. is ground in a vibration mill at temperatures < 180°K. (3–5 min), a powder with a particle size of 2–10 µg isobtained which swells well in water and gives a goodointment base (N. E. Segalova et al., Chimikofarmacevt.Z. 15, 96 [1981] [rus]; Zbl. Pharm. 121, 914 [1982]). Asolubilization procedure for obtaining water-soluble C.from fresh calf skin which is suitable for the manufacture

of cosmetic agents has been described by U. Grzegorze-wska et al. (Riv. ital. Essence, Profumi etc. 62, 388[1981]; I. P. A. 19, 3043 [1982]). Using 14C- or 125I la-beled acid-soluble C. it can be demonstrated in rat skinthat C. permeates the skin both from solutions and fromcreams (A. Huc et al., Parfums, Cosmét. Aromes 40, 87,93 [1981]; C. A. 95, 225469 [1981]). The irritant actionof e.g. shampoos can be markedly decreased by the addi-tion of C. products (P. Morganti et al., Int. J. Cosmet. Sci.5, 7 [1983]). Developmeent of artificial C. (S. St. Pierreand T. Brodniewicz, US 5,856,308, Pharm. Ind. 61, 8,733 [1999]). Properties, modifications and applications(P. Peterkova and L. Lapcik Jr., Chem. Listy 94, 371[2000] [cz]; C. A. 133, 63672 [2000]).Toxicology The CIR Panel studied the available resultson the toxicity of C. hydrolysates and finally concludedthat these products can be described as safe in the concen-trations used in cosmetic agents (R. L. Elder, J. Am. Coll.Toxicol. 4, No. 5 [1985]; Toxicol. Abstr. 9, No. 4-2329[1986]; C. A. 104, 74770 [1986]).Analytics According to C. Valenta and F. Gabor gel elec-trophoresis is suitable for quality assurance of C. prod-ucts (Sci. Pharm. 60, 267 [1992]).References R. Fleischmajer, B. R. Olsen and K. Kuhn,Biology, Chemistry and Pathology of Collagen. NewYork Academy of Sciences, Vol. 460. New York, N. Y.1985. Evaluation of collagen products for cosmetic appli-cation (Yong Peng et al., Int. J. Cosmet. Sci. 55, 327[2004]). Comparative study of the physiological proper-ties of collagen, gelatin and collagen hydrolysate as cos-metic materials (G. Y. Li et al., Int. J. Cosmet. Sci. 27 (2),101 [2005]).

(CLR)Definition Native soluble collagen with nature-identical,undamaged structure. Available with collagen concentra-tions of 0.3 % and 1 %. INCI Soluble Collagen.Applications Emulsified, aqueous and aqueous-alcoholicskin regenerating products designed to counteract dry andhelp mature skin, and prevent the skin from damagecaused by environmental influences, especially UV expo-sure. High potential to bind water, helps to promote skinhydration, accelerates skin soothing.

(Cognis, Connock, Cosmetochem, Croda, Maybrook)Definition Water-soluble products obtained by gentle hy-drolysis of collagenous proteins, which are usually of-fered as aqueous solutions. INCI Hydrolyzed Collagen,CAS 9015-54-7.Properties Aqueous solution of a collagen polypeptide,soluble in water, glycerol, propylene glycol and 50 % eth-yl alcohol.Product data pH of a 10 % solution 6.0–6.5, relativedensity 1.12–1.14, solids min. 30 %, dry weight 14.5 %,salt content max. 3.0 %.Applications For the manufacture of skin and hair careagents (0.5–5 %), protective colloid in decolorizing andwaving agents, for hair setting lotions, improves the prop-erties of hair and its styling properties. N. Radulescu et al.describe the manufacture of a powdered C. which con-tains 97–99 % collagen proteins, has a molecular weightof 500 000 to 600 000 and contains 5–7 % moisture. The

Collagen CLR

Collagen hydrolysates

Col

926

0272 438 of 29. 8. 88; Manufact. Chemist 60, No. 8, 54[1989]).Toxicology LD50 (rat) 300 mg/kg, oral LDLo (rat) 3000mg/kg. According to E. Konrad et al. M. is well toleratedby the skin, causes no sensitization and is nontoxic.

(Merck)Definition d,l-Mandelic acid.

Definition Tapioca.

Definition Obtained by extracting freshly collected seedsof the mango fruit (Mangifera indica) (9–23 % of thefruit) with hexane.Product data The crude fat and the refined fat (values inbrackets) were analyzed: mp 38° (38°), d30 0.901 (–), nD

40

1.4470 (1.4570), titer 51°, Bellier value 38.5 (–), mois-ture 0.08 % (–), AV 6.0 (0,3), SV 191 (190), IV 50 (50),unsaponifiable matter 1.5 (0.7 %) (B. L. Narasimha et al.,Cosmet. Toiletries 94, No. 1, 34 [1979]). The followingfatty acid composition (%) was determined using GLC:palmitic- 8.6, stearic- 42.2, oleic- 45.8 and linoleic acid3.4. The fat content of the seeds is 11 % on average. An-other study was performed by W. van Pee et al. (Fette,Seifen, Anstrichmittel 83, 383 [1981]). The yellow fat,mp 35–38° is very similar to cocoa butter. The study hadthe following results: 32.7–44.0 % of the triglyceridesand/or 43.7–53.4 % of all fatty acids are stearic or oleicacid. The remainder consisted of (%): palmitic- (6.7–7.0),linoleic- (3.6–6.9), arachic- (1.1–2.5) and linolenic acid(0.3–1.0). The triglycerides of the total of 9 M. types ana-lyzed consist mainly of sn-1,3-disaturated-2-oleoyl- andsn-1(3)-saturated-2,3-1,2)-dioleyl glycerides.Applications M. is suitable for consumption and as asubstitute for tallow and cocoa butter.References K. Bhattacharya and K. S. Shukla, Mangobutter in cosmetic formulations (Cosmet. Toiletries 117,65 [2002]).

Definition Tapioca.

Definition Kassave or Cassava; a Brazilian purgativeplant (Manihot utilissima), whose tubers contain a lot ofstarch and are processed to ’flour‘ suitable for consump-tion.Applications Starch may also be isolated from the tubersand may be used for food purposes or for the manufactureof e. g. tablets (binder). M. starch has good swelling prop-erties and is therefore particularly suitable for the manu-facture of tablets (C. Siregar et al., J. Pharm. Belg. 41,139 [1986]; C. A. 105, 178343 [1986]).Toxicology According to a report, frequent consumptionof M. (M. is an important foodstuff in Africa) preventsabsorption of iodine in thyroid tissue thus inducing en-demic goiter, cretinism and mental retardation. It is as-sumed that thiocyanates form from M. and may be re-sponsible for the occurrence of hypothyroidism (Dtsch.

p-Mandelic acid

Mandioca starch

Mango seed fat

Manihot starch

Manioca

Apotheker-Ztg. 118, 1017 [1978]). Importance of M. forthe economy and nutrition in Southeast Asia (J. H.Hohnholz and R. Schmid, Naturwiss. Rdsch. 35, 95[1982]).

Definition Mannitol.

Definition Polymannans. Polysaccharides of mannose(Hemicelluloses) frequently occurring in nature. Theyusually function as reserve carbohydrates of the plantsand occur as skeletal substances. M. are the main compo-nents of the seed skin of the stone of date seeds. Using theyeast Hansenula holstii W. an M. is formed which, esteri-fied with phosphoric acid, yields a phosphomannan( Phosphomannan Y-2448) which may be used as anemulsifier, dispersing and suspending and/or thickeningagent (hydrocolloid). M. is suitable as a coating agent foractivated charcoal. The granules produced may be used

orally for detoxication of blood (O. Otsubo, japan. KokaiTokkyo Koho 80 95.611 of 17. 1. 79/21. 7. 80; C. A. 94,109352 [1981]). Sterilization of M. solutions is possiblebut should not exceed 1 h; for the conditions under whichthe solutions remain sterile during storage see (N. P. Eli-nov et al., Pharm. Chem. J. [USSR] 14, 272 [1981]; Inter-nat. Pharm. Abstr. 21, No. 7-3912 [1984]).

Definition Stachyose.

Definition Crill.

Definition INCI name for the monoester of lauric acidand the anhydrides manufactured from mannitol; CAS1341-12-4.

(Amresco, Cerestar, Merck, Roquette, SPI Pharma, Spec-trum Chemical)Definition USP Mannitol, Ph Eur Mannitol, JP D-Manni-tol, D-Mannitol injection, INCI Mannitol, INN mannitol,IUPAC/WHO D-mannitol, 1,2,3,4,5,6-Hexanehexol.Manna Sugar, Mannite, D-Mannitol, CAS 69-65-8, EI-NECS/ELINCS 200-711-8. M. is an isomer of sorbitol.Empirical formula C6H14O6, mol wt 182.17. See formula,SEM pictures (100x, 1000x).

Properties M. is a white, non-hy-groscopic odorless, crystallinepowder or free flowing granuleswith a taste as sweet as sucrose. Ithas a cooling sensation in themouth. Moisture content < 0.3 %.True density d 1.514 g/cm3, pKa13.5 (at 18°), flash point > 180°.Solubility 1 g in 5.5 g of water, 18g of glycerol, 83 g of ethanol and100g of 2-propanol, practically in-soluble in ether, nD 1.333 (20°),

Manna sugar

Mannans

Manneotetrose

Mannid esters

Mannitan Laurate

Mannitol

Man

927

mp 167°, flash point > 150°, heat of solution –120.9 g/J,heat of combustion 16.57 kJ/g, [α]D25 (10 % water solu-tion) –0,40°. M. is stable, if stored in a dry form or as asterile solution. In solution, M. is neither attacked by ac-ids or alkalis in the cold, nor (in the absence of catalysts)by atmospheric oxygen. In the absence of mineral acids,bases and mineral salts M. can be heated to 250° withoutdecomposition. M. is able to bind metal ions, such as Fe-,Cu-, Al-, Mo-, Co-, Ni-, Pb-, Bi- and other ions by com-plexing, primarily in alkaline solutions (F. Köchel, Mitt.Dtsch. Pharmaz. Ges. 34, 153 [1964], G. Floret and M.M. Massa, Ann. pharmac. franç. 24, 201 [1966]; Phar-maz. Zentralhalle 106, 315 [1967]). M. shows an osmoticdiuretic activity accelerating renal excretion of drugs.Applications M. is a reduced caloric and non-cariogenicsweetener. It is suitable for water sensitive applications.For solid dosage forms it is used as sweetening agent, asplasticizer for gelatin capsules, as filler/binder in tablet,capsule and powder formulations, for direct compressionand for lyophilized preparations. A pyrogen free and en-dotoxin controlled quality is available for parenteral nu-trition, dialysis and serum applications.B. Debord et al. studied the properties of the variouspolymorphic forms of M. for their suitability as tabletbinder. The granulated α-form of M. was particularlysuitable for direct compression (Drug Dev. Ind. Pharm.13, 1519 [1988]; Internat. Pharm. Abstr. 25, No. 15-7756[1988]). J. van Dijk and H. Bijl studied the physical prop-erties of various Ms. and their effect on the disintegrationof tablets. The particle size distribution of the M. samples

has significant effects on the properties of the tablets(Congress Int. Technol. Pharm. 31th ed. 1989, 4, 323; C.A. 112, 104759 [1990]).M. is particularly suitable for the manufacture of lozeng-es, sublingual and chewing tablets (L. Geryser, Cesko-slov. Farmac. 2, 74 [1970] [cz], Zentralbl. Pharm. 109,1202 [1970]). Manufacture and control of M. infusion so-lutions (F. Köchel, Mitt. dtsch. pharmaz. Ges. 34, 153[1964], A. Przybílka, Pharmaz. Ztg. 109, 1172 [1964];Pharm. Ind. 27, 785 [1965] and B. Borkowski et al.,Farm. Pol. 25, 657 [1969]; C. A. 72, 70608 [1970]). Onheating of M. a clear, colorless, low-viscosity liquid isformed which is able to dissolve or disperse a number ofdrug substances (J. L. König, J. Pharm. Sci. 53, 188[1964]; Pharmaz. Ztg. 109, 779 [1964]). Melted M. canalso be added to other less valuable carbohydrates, e. g.cane sugar or lactose to form eutectic mixtures. Thesemixtures may also be added as solvents for active sub-stances or as dry binders (M. W. Scott, A. P. 3 341 415 of12. 2. 64/12. 9. 67; C. A. 67, 120196 [1967]). Warner-Lambert Pharmaceutical Co. (A. P. 3 145 146 of 31. 10.61/18. 8. 64; C. A. 61, 10543 [1964]) obtained a patentfor an M. spray-dried according to a special procedurewith a particle size distribution of 5–10 µm which hassignificantly improved flow properties and is thereforeprimarily intended for use in the manufacture of tablets.M. is also used as a starting material for the manufactureof polyoxyethylated emulsifiers. The foaming propertiesof soaps are improved by addition of 2 % M. The chro-mosomal aberrations induced in apical meristem cells ofthe Welsh onion e. g. by exposure to γ-radiation can belargely prevented by M. (0.001 %) (G. K. Ragimowa etal., Izv. Akad. Nauk. Az. SSR. Ser. Biol. Nauk. 3, 13[1986] [rus]; C. A. 106, 209260 [1987]). Properties anduse in medicine (S. E. Warren and R. C. Blantz, Arch. In-tern. Med. 141, 493 [1981]; Toxicol. Abstr. 5, No. 2-1097[1982]; Internat. Pharm. Abstr. 18, No. 14-3391 [1981],36 references). M. is well-proven in the treatment of se-vere and painful osteoarthritis (U. Ambanelli et al., Cur-rent Therap. Rev. 30, 85 [1981]).Toxicology M. is a foodstuff and poses no significanthazard. Ingestion of amounts above 10/20 g per dose and30/50 g per day can give a laxative effect.In tests for mutagenicity M. Ishidate jr. et al. found nopositive action for M. either in the Ames or in the chro-mosome test (Food, Chem. Toxicol. 22, 623 [1984]). Oc-currence of acute lung edemas after administration of M.(E. Hartmenn et al., Ann. Pediatr. 28, 209 [1981]; Toxi-col. Abstr. 4, No. 10-8513 [1981]). Intoxication follow-ing infusion with M. (New. Med. J. Aust. 2, 151 [1981];Internat. Pharm. Abstr. 19, No. 4-3095 [1982]), H. F.Borges (Arch. intern. Med. 142, 63 [1982]; Internat.Pharm. Abstr. 20, No. 2-0729 [1983]) and P. W. Gut-schenritter et al. (Wiss. med. J. 84, No. 5, 16 [1985]; Tox-icol. Abstr. 8, No. 8-4615 [1985]). High dose M. infu-sions may cause acute renal damage (G. M. Rabetoy etal., Ann. Pharmacother. 27, 25 [1993]; Internat. Pharm.Abstr. 30, No. 14-8335 [1993]).Analytics Determination of M. (U. Busser and W.Rosenberg, Krankenhauspharmazie 1, No. 9, 10 [1980];Internat. Pharm. Abstr. 18, No. 3-0669 [1981]). Spectro-photometric method for the determination of M. (C. H.Blomquist, J. Clin. Chem. Clin. Biochem. 19, 139[1981]). HPLC method for the determination of M., sorb-itol and xylitol in e. g. chewing gum and similar prepara-tions (E. C. Samarco et al., J. Assoc. Offic. Anal. Chem.

Man

1100

(Shin-Etsu)Definition Hydroxypropyl methyl cellulose (HPMC),cellulose, 2-hydroxypropyl methyl ether. INCI Hydrox-ypropyl Methylcellulose, CAS 9004-65-3. USP/NF, PhEur.

Properties White to light-yellow colored fibrous or gran-ular powders. Pharmacoat swells in water, forming aclear to opalescent, viscous, colloidal solution. Insolublein absolute ethanol, ether, or chloroform. Spec. gravity1.26–1.31, apparent density 0.5–0.7 g/ml (tapped), aver-age particle size 50–70 µm.Product data See table.

Applications Binder in tablet manufacture and tabletcoating (aqueous or organic) for taste-masking, improve-ment of hardness, sub-coating for sugarcoating and enter-ic coating.Toxicology Toxicity (♀ and ♂ Wistar rats) LD50 > 15 g/kg, subacute toxicity (♀ and ♂ rats, Wistar strain, oralapplication of 1.25, 2.50 and 5.0 g/kg for 30 days) nochanges (body weight, food ingestion, organic weight,analysis of blood and urine, histopathological tests),chronic toxicity (♀ and ♂ Wistar rats, administration of1.25, 2.50 and 5.00 g/kg for 6 months) no changes. Me-tabolism: ♂ Wistar rats, oral administration of 14C-P; 100mg/kg, oral. Within 72 h 0.39 % in the urine and 98.92 %14C-P. in the feces.Analytics Analytical methods described in the pharmaco-poeias.

(Croda)

Pharmacoat

Pharmacoat 603 606 615 904pH all types 5.5–8.0Apparent

viscosity2.4–3.6 4.6–7.2 12.0–18.0 3.2–4.8

Loss on drying not more than 5 %Residue on

ignitionnot more than 1 % (EP)

not more than 1.5 % (USP)

Arsenic below 3 ppmHeavy metals below 10 ppmChlorides not more than 0.5 %Methoxyl

content28.0–

30.0 %19.0–

24.0 %

Hydroxypropyl content

7.0–12.0 %

4.0–12.0 %

Pharmalan

Definition Trade name for pharmaceutical grade lanolin,manufactured to GMP standards. Conforms to Ph Eurmonograph for wool fat.

(ISP)Definition Trade name for N-methyl-2-pyrrollidonecGMP grade.Product data Liquid, boiling point 202°, specific density(25°) 1.027, viscosity (25°) 1.65 mPa·s.Applications Broad spectrum drug solubilizer. Increasessolubility, rate of solubilization and solution stabiliy ofdrugs in aqueous solution.

(DMV)Definition Milled, sieved and spray-dried types oflactose. Lactose is a disaccharide, and normally avail-

able as monohydrate.4’-(β-D-Galactopyranosido)-D-glucopyranose, 1-(β)-ga-lactosido-(1-5)-4-glucose. Lactobiose, Milk sugar, Sac-charum Lactis. Ph Eur, USP/NF, JP. CAS 63-42-3. Em-pirical formula C12H22O11 ‚ 1 H2O. Mol wt 342.30.Structural formula see Lactose.Properties White, water soluble powders with a slightlysweet taste. No odor.Product data See tables.Applications The sieved types of lactose are used as fill-er in hard-gelatin capsules, flow-improving agent and di-luent in direct compression formulations. Milled typesare used as filler in wet granulation processes. The DCLtypes are showing, based on the manufacturing proce-dures, a very good flow and tablettability. Mainly usedfor tablets, capsules and sachets. The two products DCL21 and DCL 40 are in addition applied in chewables, mul-tivitamin tablets, DCL 40 also for high dosage forms, be-cause they form tablets with a high tablet strength.Single products6 sieved types: P. M 50, M 80, M 90, M 100, M 110, andM 125.4 milled types: P. M 150, M 200, M 350, and M 450.P. DCL 11: spray-dried lactose, DCL 15: granulated lac-tose, DCL 21: anhydrous lactose (β-form of anhydrouslactose is mainly present), DCL 40: compound lactose(95 % anhydrous lactose and 5 % lactitol).

Pharmasolve

Pharmatose grades

Pharmatose M 150 M 200 M 350 M 450BET surface area (m2/g)

0.45 0.50 0.60 1.0

Bulk density (g/l)

580 550 500 470

Bulk density (tapped, g/l)

890 850 820 770

Particle size distribution< 45 µm max. 50 % 50–65 % min. 60 % min. 90 %< 63 µm – – – min. 98 %< 100 µm min. 70 % min. 90 % min. 96 % –< 150 µm min. 85 % min. 96 % – 100 %< 250 µm – min. 96 % 100 % –< 315 µm 100 % 99–100 % – –

Pha

1101

(DMV)Definition α-Lactose monohydrate for inhalation, PhEur, USP/NF, JP.Properties α-Lactose monohydrate designed for the for-mulation of dry powder inhalations, selected particle sizerange by sieving.Applications Carrier in dry powder inhalation systems.

(DMV)Definition Spray dried lactose, Ph Eur, USP/NF, JP.

Properties Spherical particles of nearly uniform size, ex-cellent flowability and compressibility. See SEM picture.Product data Particle size range: < 15 % < 45 µm, 30–60% < 100 µm, 98–100 % < 250 µm.Applications Filler/binder in direct compression, carrierfor interactive mixtures.

(DMV)Definition Granulated α-lactose monohydrate, Ph Eur,USP/NF, JP.

Pharmatose 325 M

Pharmatose DCL11

Pharmatose DCL15

Properties Agglomerated pure α-lactose monohydrate,showing good compression and flow properties. SeeSEM picture.Product data Particle size range: 10–30 % < 75 µm, 40–70 % < 150 µm, 90–100 % < 355 µm, 100 % < 500 µm.Applications Filler/binder for direct compression, carrierfor capsule and sachet filling.

(DMV)Definition Anhydrous lactose containing 80 % β-lactose,Ph Eur, USP/NF, JP.

Pharmatose DCL21

PhaPharmatose M 50 M 80 M 90 M 100 M 110 M 125Angle of repose 36° 38° 39° 39° 40° 44°Bulk density (g/l) 725 760 760 750 730 680Bulk density (tapped, g/l) 825 910 910 900 890 870Particle size distribution (%)

< 45 µm – – – – – max. 40< 63 µm – – max. 10 max. 15 max. 20 40–70< 100 µm – max. 20 15–30 – 30–60 min. 90< 150 µm – – 55–90 60–80 75–90 –< 200 µm max. 20 – – – – –< 250 µm – 70–90 – min. 99 – –< 315 µm – min. 95 100 – 100 100< 400 µm min. 80 – – – – –

1146

Definition Nonoxynol-(10)-Carboxylic Acid.

Definition Nonoxynol-6 Phosphate.

Definition Sodium salts of complex mixtures of esters ofphosphoric acid and Nonoxynol. INCI Sodium Nonox-ynol-n Phosphate, CAS 9014-90-8.

(Dow Chemical)Definition PEG-16 octyl phenyl ether, polyoxyethyl-ene(16)octyl phenyl ether, INCI Octoxynol-16, CAS9004-87-9, 9036-19-5, an ethoxylated alkyl phenol,C8H17C6H4(OCH2CH2)nOH, n has an average value of 16.The product is commercially available under the nameTriton X-165.

(Dow Chemical, Nikko)Definition PEG-30 octyl phenyl ether, polyoxyethyl-ene(30)octyl phenyl ether, INCI Octoxynol-30, CAS9004-87-9, 9036-19-5, an ethoxylated alkyl phenol,C8H17C6H4(OCH2CH2)nOH, n has an average value of 30.The product is commercially available under the nameTriton X-305.

(Dow Chemical)Definition PEG-70 octyl phenyl ether, polyoxyethyl-ene(70)octyl phenyl ether, INCI Octoxynol-16, CAS9004-87-9, 9036-19-5, an ethoxylated alkyl phenol,C8H17C6H4(OCH2CH2)nOH, n has an average value of 16.The product is commercially available under the nameTriton X-705.

(Dow Chemical)Definition PEG-8 octyl phenyl ether, polyoxyethyl-ene(8)octyl phenyl ether, INCI Octoxynol-8, CAS 9004-87-9, 9036-19-5, an ethoxylated alkyl phenol, C8H17C6H4(OCH2CH2)nOH, n has an average value of 8. Theproduct is commercially available under the name TritonX-114.

Definition USP, Macrogol Ointment BP, UnguentumPolyethylenglycoli. There are various possible formula-tions. One such consists of equal parts of polyethyleneglycol 300 and polyethylene glycol 1500 which aremixed with heating and stirred until they have cooled. Toobtain a uniform, readily spreadable ointment theamounts of the polyethylene glycols may be varied by upto 10 % of their weight. This formulation is more suitablethan P. manufactured in accordance with USP or the Aus-

Polyethylene glycol(500)nonyl phenyl ether carboxylic acid

Polyethylene glycol(300)nonyl phenyl ether phosphate

Polyethylene glycol(n)nonyl phenyl ether phosphate, sodium salt

Polyethylene glycol(16)octyl phenyl ether

Polyethylene glycol(30)octyl phenyl ether

Polyethylene glycol(70)octyl phenyl ether

Polyethylene glycol(400)octyl phenyl ether

Polyethylene glycol ointment

trian Pharmacopoeia, which is too hard, especially in thecold. K. E. Schulte and M. A. Kassem (Pharm. Acta Hel-vetiae 39, 383 [1964]) recommend a P. of polyethyleneglycol 400, 1500 and 4000 (57,5:20:22,5). To improvethe water absorbency of a P. which consists of equal partsof P. 4000 and P. 400 5 % cetyl alcohol may be added.According to W. Chandranondnaiwinit and E. B. Som-mers even better results are achieved, if 0.5 % anhydrous,non-neutralized Carbopol 934 is added (J. Pharm. Sci.55, 1221 [1966]). Water absorbency is increased to 48 %by this additive. – Lanogen 1500.References W. Kern, O. Salzmann, H. Rath and Fr. Salz-er, Pharm. Ind. 18, 3 (1956).

Definition The polyethylene glycol-100-amide of oleicacid (I), n = 2. INCI PEG-2 Oleamide, CAS 20429-33-8.

(Akzo Nobel)Definition A quaternary ammonium salt (I), n is approx.2. INCI PEG-2 Oleammonium Chloride. Ethoquad O/12H ( Ethoquad).

Definition A polyethylene glycol ester of oleic acid,INCI PEG-15 Oleate, CAS 9004-96-0.

(Amerchol)Definition PEG 16 oleyl ether, polyoxyethylene(16)oleylether, INCI Oleth-16; is the polyethylene glycol ether ofoleyl alcohol, CH3(CH2)7CH = CH(CH2)7CH2(OCH2CH2)nOH, n has a value of approx. 16. The product iscommercially available under the name Solulan 16.Oleth-n.

Definition The sodium salt of the sulfate ester of thepolyethylene glycol ether of oleyl alcohol, INCI SodiumOleth Sulfate, CAS 42415-80-5.

Definition INCI name for a polyethylene glycol(500)-de-rivative of the mono- and diglycerides of olive oil.

Definition Crovol PK 40.

Polyethylene glycol(100)oleamide

Polyethylene glycol(100)oleammonium chloride

Polyethylene glycol(15)oleate

Polyethylene glycol(16)oleyl ether

Polyethylene glycol(1-4)oleyl ether sulfate, sodium salt

Polyethylene Glycol(500)-Olive Oil Glycerides

Polyethylene glycol(12)palm kernel oil glycerides

Pol

1147

Definition Crovol PK 70.

Definition Palm oil, hydrogenated and ethoxylated.

Definition Polyethylene glycols.

Definition A nonionic biodegradable liquid containing100 % active substance which is used as an emulsifierand solubilizer, and as a skin and/or hair conditioner incosmetic preparations.

Definition Polyoxyethylene(10)propylene glycol, INCIPEG-10 propylene gly-col, a polyethylene glycolether of propylene glycol(I), x + y has an averagevalue of 10.

Definition INCI name for a polymer of ethylene oxide,H(OCH2CH2)nOH. The mol wt ranges between 1 · 105

and 5 · 106.Properties P. resins are white, granular, freely flowingpowders with a characteristic odor. They can be dispersedin water.Product data pH value of a 5 % aqueous dispersion ap-prox. 10.0, viscosity of a 5 % aqueous dispersion 550–900 mPa·s, loss on drying max. 1.0, ash content max. 0.8%.

(Uniqema)Properties A light yellow to brownish yellow, oily liquidwith a faint odor and a bitter taste.Product data D 1.082, viscosity (20°) 680.38 cP, pH6.25, AV 0.87, SV 49.69, OHV 72.05, IV 21.21, loss ondrying 2.4 %, combustion residue 0.6 %.Applications Solubilizer and nonionic emulsifier.Toxicology Although a report of the CTFA, published inJanuary 1992, emphasizes that P. has not, so far, beenshown to be carcinogenic, or dangerous, the NTP (Na-tional Toxicological Program) has called for further toxi-cological testing of P. to supplement the available data.Analytics Detection of P. and other esters in foodstuffs(TLC on silica gel) (J. M. Murphy and C. C. Scott, Ana-lyst 94, 481 [1969]; Zbl. Pharm. 109, 409 [1970]).

Definition An ethoxylated sorbitan monoester of stearicacid; it contains about 3 mol of ethylene oxide; INCIPEG-3 Sorbitan Stearate, CAS 9005-67-8.

Polyethylene glycol(45)palm kernel oil glycerides

Polyethylene glycol(1000)-palm oil (hydrogenated)

Polyethylene glycol-paraffin oil gels

Polyethylene glycol-200-pelargonate

Polyethylene glycol(500)propylene glycol

Polyethylene Glycol Resin

Polyethylene glycol sorbitan (mono)oleate

Polyethylene glycol(3)sorbitan stearate

Definition Sorbeth-20, RD 977058-26-6, polyoxyethyl-ene(20)sorbitol ether, PEG-20 sorbitol ether, EthosperseSL-20, an ethoxylated ether of sorbitol, containing ap-prox. 20 mol EO were reacted.

Definition If polyethylene glycol (mol wt 200–600) isheated with sorbitol in the presence of water polymeriza-tion ensues. The water-soluble polymers obtained werestudied by N. M. Mursi et al. (Pharm. Ind. 39, 918[1977]); they are reported to be suitable as a base for themanufacture of pharmaceutical preparations.

(Goldschmidt)Definition A polyethylene glycol ester of stearic acid (I),n has an average value of 3. The product is commerciallyavailable e. g. under the name Tegin D 1102. INCI PEG-3 Stearate, CAS 9004-99-3, 10233-24-6.

Definition A polyethylene glycol ether of stearic acid,INCI PEG-120 Stearate, CAS 9004-99-3.

Definition Cremophor S 9.

Definition The ‘Final report on the safety assessment’has been published in the USA for P. (x = 2, 6, 8, 12, 20,32, 40, 50, 100 and 150) (K. H. Beyer jr. et al., J. Amer.Coll. Toxicol. 2, 17 [1983] [42 references]; C. A. 100,91095 [1984]). P. are described as ‘safe cosmetic ingredi-ents‘.

Definition Neutronyx 332.

(Akzo Nobel)Definition A quaternary ammonium salt (I), x + y is ap-prox. 2. INCI PEG-2-Stearmoniumchloride, CAS 60687-87-8. Ethoquad 18/12 ( Ethoquad).

(Clariant)

Polyethylene glycol(1000)sorbitol ether

Polyethylene glycol-sorbitol-macromolecules

Polyethylene glycol(3)stearate

Polyethylene glycol(120)stearate

Polyethylene glycol-400-stearate

Polyethylene glycol-x stearates

Polyethylene glycol-1000-stearic acid ester

Polyethylene glycol(100)stearmonium chloride

Polyethylene glycol(5)stearyl ammonium lactate

Pol

1442

T. HB7, sodium alkyl (C9–13) sulfate, activity 40 %, flu-id liquid.T. ALS70, ammonium lauryl (C12–14) sulfate, activity70 %, viscous gel.T. ALS25, ammonium lauryl (C12–14) sulfate, activity25 %, fluid liquid.

Dried products:T. 12P, sodium lauryl (C12) sulfate, activity 94 %, finepowder.T. USP94, sodium lauryl (C12–14) sulfate, activity 94 %,fine powder.T. USP97, sodium lauryl (C12–14) sulfate, activity 97 %,fine powder.T. A97, sodium lauryl (C12–14) sulfate, activity 90 %,needles.T. A795 S, sodium lauryl (C12–14) sulfate, activity 94%, needles.T. PCL 94, sodium lauryl (C12–18) sulfate, activity 93%, fine powder.T. ACL79, sodium lauryl (C12–18) sulfate, activity 90%, needles.T. CO A795, sodium coco (C12–18) sulfate, activity 93%, needles.T. SPKA795P, sodium/potassium lauryl (C12–14) sul-fate, activity 93 %, needles.T. A13-15, sodium tridecyl (C13–15) sulfate, activity 85%, needles.

(Tensachem)Definition Trade name for waxes.Applications Waxes for toiletries, hair care and skin careproducts.Single productsT. CSA P, cetostearyl alcohol non-ionic wax, activity100 %, pellets.T. N21 P, blend of cetostearyl alcohol and non-ionicemulsifier, activity 100 %, pellets.T. N200 P, blend of cetostearyl alcohol and non-ionicemulsifier, activity 100 %, pellets.T. SXBP P, blend of cetostearyl alcohol and anionicemulsifier, activity 100 %, pellets.

Definition Abbreviation for transepidermal water loss(Perspiratio insensibilis).

Definition A substance has teratogenic effects, if it caus-es abnormalities in an embryo because of treatment of themother animal with the substance during pregnancy.

Definition The para (1,4) isomer of phthalic acid dialkylester.

(Dow Chemical, Union Carbide)Definition Trade name for various anionic and non-ionicsurface-active substances.

Tensowax grades

TEPD

Teratogenicity

Terephthalic acid ester

Tergitol

Applications Undiluted T. should not be brought intocontact with skin; they improve the surface activity ofother surface-active agents and particularly the antisepticproperties of acid, antiseptic preparations and the actionof penicillin. The anionic types 4, 7 and 08 are used fordestroying emulsions in the manufacture of penicillin,types 4 to 7 form soluble complexes with streptomycinand similar antibiotics in organic solvents and are hencesuitable for isolating streptomycin etc. In bactericidalpreparations the nonionic types XD and NPX enhancedispersion of the ingredients. Solutions of amine soapshampoos are improved by addition of T. type NPX orXD; they can be rinsed off more easily. Hair conditionersare improved by addition of T. type XD (proposed formu-lation: Ucon Fluid LB-1715 50.0, polyethylene glycol1540-monostearate 3.75, T. type XD 1.25 and water45.0).

Single products1. Nonionic types (100 % active substance, unless other-wise specified).NP-14. Nonyl polyethylene glycol ether with 4 moleculesEO, an almost colorless liquid, solubility in water < 0.01%, readily soluble in fats and solvents, pH (in 0.1 %aqueous solution) 6.2, freezing point –40°, dA 1.031, vis-cosity 448 cSt (20°), LD50 (rat, oral) 4.29 ml/kg, mildskin irritation (rabbit), reaction on the rabbit eye after ap-plication of a 15 % solution.NP-27. Nonyl phenyl polyethylene glycol ether with 7molecules EO, an almost colorless liquid, solubility inwater 20 %, soluble in fats and various solvents, dispers-ible in paraffin oil, pH 6.1, freezing point –5 to –7°, dA1.055, viscosity 338 cSt (20°), LD50 (rat, oral) 3.67 ml/kg,no skin irritation (rabbits), reaction on the rabbit eye afterapplication of a 15 % solution.TP-9. Nonyl phenyl polyethylene glycol ether with 9molecules EO, colorless liquid, soluble in water, sparing-ly soluble in fats, insoluble in paraffin oil, soluble in vari-ous solvents, pH 5.2, freezing point 6°, dA 1.057, viscos-ity 318 cSt (20°), LD50 (rat, oral) 2.6 ml/kg, mild skinirritation (rabbit), reaction on the rabit eye after applica-tion of a 5 % solution.NPX. Nonyl phenyl polyethylene glycol ether with 10.5molecules EO, practically colorless liquid, soluble in wa-ter, sparingly soluble in fats, soluble in various solvents,insoluble in paraffin oil, pH 7.5, freezing point 5–7°, dA1.063, viscosity 327 cSt (20°), LD50 (rat, oral) 1.31 g/kg,mild skin irritation (rabbit), reaction on the rabbit eye fol-lowing application of solutions > 5 %.NP-35. Nonyl phenyl polyethylene glycol ether with 15mol EO, a semisolid mass, soluble in water and varioussolvents, sparingly soluble in fats, insoluble in mineraloil, pH 6.1, sp 25–27°, dP 1.065, viscosity 144 cSt (38°),LD50 (rat, oral) 4.00 g/kg, no skin irritation (rabbit), reac-tion on the rabbit eye after application of 100 % sub-stance.NP-40. Nonyl phenyl polyethylene glycol ether with 20molecules EO, a white solid, soluble in water and varioussolvents, insoluble in fats and mineral oil, pH 6.6, sp 36–38°, dP 1.077, viscosity 55 cSt (65°), LD50 (rat, oral)15.9 g/kg, no skin irritation (rabbit), reaction on the rabbiteye after application of 100 % substance.TMN. Trimethyl nonyl ether of polyethylene glycol with6 mol EO, a pale yellow liquid, 90 % active substance,soluble in water, pH 6.8, sp 15–17°, dA 1.024, viscosity105 cSt (20°), LD50 (rat, oral) 3.26 g/kg, no skin irritation

Ten

1443

(rabbit), reaction on the rabbit eye after application of a 1% solution.12-P-12. A nonionic dodecyl phenol ethylene oxide con-densate, an all purpose cleaning and wetting agent withgood dispersing and emulsifying properties, turbiditypoint (0.5 % aqueous solution) 60–65°, compatible withsoaps, anionic, cationic and nonionic emulsifiers.XD. Polyethylene glycol ether, soft, semisolid mass, sol-uble in water and various solvents, insoluble in fats andmineral oil, pH 6.0, sp 28–38°, dP 1.053, viscosity 428cSt (38°), LD50 (rat, oral) 5.66 g/kg, no skin irritation(rabbit), reaction on the rabbit eye after application of100 % substance.XH. Polyalkylene glycol ether, odorless solid, soluble inwater, pH 6.0, sp 36–40°, dO 1.0344, viscosity 325 cSt(38°), LD50 (rat, oral) 22.4 g/kg (25 % aqueous solution),mild skin irritation (rabbit), reaction on the rabbit eye af-ter application of an aqueous 25 % solution.

2. Anionic types7. 25 % aqueous solution of sodium heptadecyl sulfate,C4H9CH(C2H5)C2H3(SO4Na)C2H4CH(C2H5)2, colorlessliquid, pH 5.3, dA 1.046, LD50 (rat, oral) 5.66 ml/kg, se-vere skin irritation (rabbit), reaction on the rabbit eye af-ter application of a 5 % solution.P-28. 25 % aqueous solution of sodium di(2-ethylhexyl)-phosphate, [C4H9·CH(C2H5)CH2 ]2 NaPO4, brown liquid,pH 6.7, dA 1.034, LD50 (rat, oral) 7.72 ml/kg, severe skinirritation (rabbit), reaction on the rabbbit eye after appli-cation of a 5 % solution.4. 25 % aqueous solution of sodium tetradecyl sulfate,C4H9CH(C2H5)C2H4CH(SO4Na) · CH2 · CH(CH3)2, prac-tically colorless liquid, pH 8.5, dA 1.056, LD50 (rat, oral)4.95 ml/kg, severe skin irritation (rabbit), reaction on therabbit eye after application of a 5 % solution.08. 38 % aqueous solution of sodium-2-ethyl hexyl sul-fate, C4H9CH(C2H5)CH2-SO4 · Na, colorless liquid, pH7.3, dA 1.144, LD50 (rat, oral) 10.32 ml/kg, severe skinirritation (rabbit), reaction on the rabbit eye after applica-tion of 0.005 ml of the 100 % substance.

(Dow Chemical, Union Carbide)Definition A group of surface-active substances obtainedfrom straight-chain secondary alcohols usually contain-ing 11–15 C-atoms and manufactured from petrol hydro-carbons by ethoxylation and, in some cases, sulfation.In the product T. nonionic 15-S-9 e. g. the number 15 in-dicates that the secondary alcohol contains 11–15 carbonatoms, while the number 9 indicates the number of molEO (x). The anionic product T. 15-S-3 A is manufacturedfrom a secondary alcohol which contains 11–15 carbonatoms, x is 3 and the final letter indicates that M is theammonium salt. All products are readily biodegradable.

Single products(a) Nonionic products (100 % active substance):T. 15-S-3, mol wt 332, turbidity point (in 1 % aqueoussolution) indeterminable, sp –30°, apparent density (d)0.924, viscosity (20°) 37 cSt, HLB 9.0, flash point 370°,insoluble in water (25°).T. 15-S-5, mol wt 420, turbidity point indeterminable, sp–15°, apparent density (d.) 0.970, viscosity (20°) 51 cSt,flash point 410°, soluble in water.

Tergitol S series

T. 15-S-7, mol wt 508, turbidity point 37°, sp 7°, appar-ent density (d) 0.994, viscosity (20°) 67 cSt, HLB 12.8,flash point 440°, soluble in water, LD50 (rat, oral) 3.25ml/kg, cutaneous toxicity (LD50, rabbit skin) 3.18 mg/kg,moderate irritation is observed on rabbit skin, serious irri-tation on the rabbit eye.T. 15-S-9, mol wt 596, turbidity point 60°, sp 13°, appar-ent density (d) 1.06, viscosity (20°) 86 cSt, HLB 13, flashpoint 470°, soluble in water, LD50 (rat, oral) 2.38 ml/kg,cutaneous toxicity (LD50, rabbit skin) 2.00 ml/kg, mild ir-ritation is observed on rabbit skin but serious irritation onthe rabbit eye.T. 15-S-12, mol wt 728, turbidity point 90°, sp 17°, ap-parent density (d) 1.023, viscosity (20°) 120 cSt, HLB15.0, flash point 460°, soluble in water, LD50 (rat, oral)3.36 ml/kg, cutaneous toxicity (LD50, rabbit skin) 4.00ml/kg, only mild irritation is observed on rabbit skin butserious irritation on the rabbit eye.

(b) Anionic productsT. 15-S-3A, mol wt 435. 60 % active substance, sp –36°,apparent density (dA) 1.039, viscosity (20°) 43 cSt, flashpoint 195°, soluble in water, LD50 (rat, oral) 17.2 ml/kg,cutaneous toxicity (LD50, rabbit skin) > 10 ml/kg, onlymild reactions are observed on rabbit skin and moderatereactions on the rabbit eye.T. 15-S-3S, mol wt 440. 60 % active substance, sp –45°,apparent density (d) 1.057, viscosity (20°) 49 cSt, flashpoint 172°, soluble in water, LD50 (rat, oral) 3.25 ml/kg,cutaneous toxicity (LD50, rabbit skin) 2.83 ml/kg. Seriousirritation is observed both on rabbit skin and on the rabbiteye. The products T.15-S-9 and T. 15-S-3A were testedin a 10 % concentration for skin tolerance in 50 individu-als. None of the products caused irritation or sensitiza-tion.

Definition Lemnian earth, seal earth, Siegelerde. An oldname for bolus, an aluminum silicate. According to P.H. Graepel S. was used in the middle age almost as acure-all (pta in der prakt. Pharm. 9, 297 [1980]) and as anantidote.

Definition Kieselguhr.

(Acros)Definition 2-Methyl-3,4,5,6-tetrabromophenol, (I), CAS576-55-6, C7H4OBr4, mol wt 423.8. Properties Light beige, practically odorless, crystallinepowder, mp 205–208°, soluble in acetone, ethyl alcohol,ethylene chloride, chloroform and toluene, soluble in di-

lute bases, insoluble in water,content min. 98.5 %.Applications T. is an antimi-crobial agent with good inhib-iting effects on Gram-positivebacteria. The minimal inhibi-tory concentration againstStaphylococcus aureus, S.epidermidis, StreptococcusAronson, S. pyogenes and

Terra sigillata

Terra silicea

Tetrabromo-o-cresol

Tet