Specific surface area: 0.25 m2/g

to 2.5 mg/kg body-weight for saccharin, including its salts.(3) In the UK, the Committee on Toxicity of Chemicals in Food, Consumer Products, and the Environment (COT) has set an acceptable daily intake for saccharin and its salts (expressed as saccharin sodium) at up to 5 mg/kg body-weight.(4)

LD50 (mouse, oral): 17.5 g/kg(5) LD50 (rat, IP): 7.1 g/kg

LD50 (rat, oral): 14.2 g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection and a dust mask are recommended.

Regulatory Status

Accepted for use as a food additive in Europe; ‘E954’ is applied to both saccharin and saccharin salts. Included in the FDA Inactive Ingredients Guide (buccal and dental preparations; IM and IV injections; oral and topical preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Alitame; saccharin.

Comments

The perceived intensity of sweeteners relative to sucrose depends upon their concentration, temperature of tasting, and pH, and on the flavor and texture of the product concerned.

Saccharin Sodium 643

Intense sweetening agents will not replace bulk, textural, or preservative characteristics of sugar if sugar is removed from a formulation.

Synergistic effects for combinations of sweeteners have been reported. Saccharin sodium is often used in combination with cyclamates and aspartame since the saccharin sodium content may be reduced to minimize any aftertaste.

Specific References

Kloesel L. Sugar substitutes. Int J Pharm Compound 2000; 4(2): 86–87.

Ungphaiboon S, Maitani Y. In vitro permeation studies of triamcinolone acetonide mouthwashes. Int J Pharm 2001; 220(1–2): 111–117.

FAO/WHO. Evaluation of certain food additives and contami- nants. Twenty-eighth report of the FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1984; No. 710.

Food Advisory Committee. FAC further advice on saccharin. FdAC/REP/9. London: MAFF, 1990.



Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 3277.

See Saccharin for further references.

General References

Anonymous. Saccharin is safe. Chem Br 2001; 37(4): 18.

Lindley MG. Sweetener markets, marketing and product developments. In: Marie S, Piggott JR, eds. Handbook of Sweeteners. Glasgow: Blackie, 1991: 186.

Authors

SC Owen.

Date of Revision

11 August 2005.

Saponite

Nonproprietary Names

None adopted.

Synonyms

Afrodit; aluminum-saponite; auxite; cathkinite; ferroan sapo- nite; griffithite; licianite; lucianite.

Chemical Name and CAS Registry Number

Saponite [1319-41-1]

Empirical Formula and Molecular Weight

(Ca0.5Na)0.3(Mg,Fe2+)3(Si,Al)4O10(OH)2·4H2O   ≈480

Saponite is a naturally occurring phyllosilicate clay of the smectite (montmorillonite) group. It is a magnesium-rich hydrated aluminum silicate and is present as a component of some commercial magnesium aluminum silicate clays. Saponite is a mineral with an approximate empirical formula owing to the variability in cation substitution; see Table I.

Table I: Approximate composition of saponite based on chemical analysis.

 

Component Wt %    

SiO2 37.5    

Al2O3 10.6    

MgO 18.9    

CaO 1.2    

Na2O 0.65    

FeO 11.2    

H2O 18.8  

Structural Formula

Saponite is a natural mineral clay that is a hydrous silicate of aluminum and magnesium. It occurs in soft, amorphous masses in the cavities of certain rocks.

Saponite is composed of two tetrahedral layers formed by phylosilicate sheets and one octahedral layer. Common impurities include manganese, nickel, phosphorus, potassium, and titanium.

See Section 4.

Functional Category

Adsorbent; emulsifying agent; viscosity-increasing agent.

Applications in Pharmaceutical Formulation or Technology

Saponite is a colloidal material present in various naturally occurring clays such as magnesium aluminum silicates(1) and is therefore suitable for use in pharmaceutical formulation applications as an adsorbent, viscosity-increasing agent, suspending agent, or as an oil-in-water emulsifying agent. It is

a swelling clay with a low cation exchange capacity, and when mixed with water it displays thixotropic properties. Saponite is similar to bentonite, and has the capacity to adsorb drugs through cationic exchange.(2) Drug–saponite adsorbates show a slight reduction in dissolution rate.(2) Saponite is useful in the formulation of gastrointestinal X-ray contrast agents(3) and formulations designed for sustained drug delivery to the gastrointestinal tract.(4)

Description

Saponite occurs as a white to off-white, dull powder composed of fine-grained crystals of colloidal size. The material is greasy or soapy to the touch and swells on the addition of water.

Pharmacopeial Specifications

—

Typical Properties

Density (true): 2.67 g/cm3

Crystal data: monoclinic; a = 5.3, b = 9.14, c = 16.9, b ≈ 978.

Hardness (Mohs): 1–2

Stability and Storage Conditions

Saponite is a stable material and should be stored in a cool, dry place.

Incompatibilities

—

Method of Manufacture

Naturally occurring saponite is mined from deposits in various localities around the world.

Safety

Saponite is a natural clay mineral that is not acutely toxic; therefore, no toxicity values have been established. However, it may contain small amounts of crystalline silica in the form of quartz. Chronic exposure to crystalline silica can have adverse effects on the respiratory system. EU labeling states the material is not classified as dangerous.

Saponite dust can be irritating to the respiratory tract and eyes. Contact with this material may cause drying of the skin.

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material being handled. Avoid generating and breathing dust and use eye protection. For dusty conditions, eye protection, gloves, and a dust mask are recommended. The occupational exposure limits for saponite are 5 mg/m3 (respir- able) PEL-TWA, 3 mg/m3 (respirable) TLV-TWA, and 10 mg/m3 (inhalable) dust TLV-TWA.

Saponite 645

Regulatory Status

Reported in the EPA TSCA Inventory.

Related Substances

Attapulgite; bentonite; kaolin; hectorite; magnesium aluminum silicate; talc.

Comments

The EINECS number for saponite is 215-289-0.

Specific References

Browne JE, Feldkamp JR, White JL, Hem SL. Characterization and adsorptive properties of pharmaceutical grade clays. J Pharm Sci 1980; 69(7): 816–823.

El-Gindy GA, Ali AS, El-Shinnawi OM. Preparation and formula- tion of sustained-release terbutaline sulphate microcapsules. Bull Pharm Sci Assiut Univ 2000; 23(1): 55–63.

Ruddy SB, Eickhoff WM, Liversidge G, Cooper ER. Formulations of oral gastrointestinal therapeutic agents in combination with pharmaceutically acceptable clays. International Patent WO96/ 2096; 1996.



Ruddy SB, McIntire GL, Roberts ME, Caulifield TJ, Cooper ER. X-ray contrast compositions containing iodoaniline derivatives and pharmaceutically acceptable clays. United States Patent No. 5,424,056; 1995.

General References

Cormleyu I, Addison J. The in vitro cytotoxicity of some standard clay mineral dusts of respirable size. Clay Miner 1983; 18(2): 153–163. Polon JA. Mechanisms of thickening by inorganic agents. J Soc Cosmet

Chem 1970; 21: 347–363.

Post JL. Saponite from near Ballarat, California. Clays Clay Miner

1984; 32: 147–153.

Viseras C, Lopez-Galindo A. Characteristics of pharmaceutical grade phylosilicate powders. Pharm Dev Technol 2000; 5(1): 47–52.

Authors

PE Luner.

Date of Revision

18 August 2005.

Sesame Oil

Nonproprietary Names

BP: Refined sesame oil JP: Sesame oil

PhEur: Sesami oleum raffinatum USPNF: Sesame oil

Synonyms

Benne oil; gingelly oil; gingili oil; jinjili oil; Lipovol SES; teel oil.

Chemical Name and CAS Registry Number

Sesame oil [8008-74-0]

Empirical Formula and Molecular Weight

A typical analysis of refined sesame oil indicates the composi- tion of the acids, present as glycerides, to be: arachidic acid 0.8%; linoleic acid 40.4%; oleic acid 45.4%; palmitic acid 9.1%; and stearic acid 4.3%. Sesamin, a complex cyclic ether, and sesamolin, a glycoside, are also present in small amounts.

Note that other reported analyses may vary slightly from that above.(1)

The monographs for Sesame Oil in the USPNF 23 and Refined Sesame Oil in the PhEur 2005 specify the acceptable range of eight triglycerides found in sesame oil.

Structural Formula

See Section 4.

Functional Category

Oleaginous vehicle; solvent.

(tahini), composed of crushed sesame seeds in sesame oil, has been investigated as a novel suspending agent.(14)

Sesame oil is additionally used as an edible oil and in the preparation of oleomargarine.

Description

Refined sesame oil is a clear, pale-yellow colored liquid with a slight, pleasant odor and a bland taste. It solidifies to a soft mass at about —48C.

Pharmacopeial Specifications

See Table I.

Table I:  Pharmacopeial specifications for sesame oil.

Applications in Pharmaceutical Formulation or Technology

The major use of sesame oil in pharmaceutical formulations is

matter Composition of

triglycerides



— + +

as a solvent in the preparation of sustained-release intramus-

Alkaline impurities — + —

cular injections of steroids, such as estradiol valerate, hydroxy- progesterone caproate, testosterone enanthate, and nandrolone

Organic volatile

impurities

— — +

(a)

decanoate,(2) or other oil-soluble drug substances, such as, the decanoates or enanthate esters of fluphenazine. The disap- pearance of sesame oil from the injection site, following subcutaneous or intramuscular administration to pigs, has been reported to have a half-life of about 23 days.(3)

Sesame oil may be used as a solvent in the preparation of subcutaneous injections,(4) oral capsules,(5,6) rectal supposi- tories,(7) and ophthalmic preparations;(8) it may also be used in the formulation of suspensions(9) and emulsions.(9–11) Multiple- emulsion formulations, in which sesame oil was one of the oil phases incorporated, have been investigated as a prolonged- release system for rifampicin;(12) microemulsions containing sesame oil have been prepared for the transdermal delivery of ketoprofen.(13) Sesame oil has also been used in the preparation of liniments, pastes, ointments, and soaps. A sesame paste

Water — 40.05% —

(a) In sesame oil intended for parenteral use.

Typical Properties

Density: 0.916–0.920 g/cm3 Flash point: 3388C (open cup) Freezing point: —58C

Refractive index: n40 = 1.4650–1.4665

Solubility: insoluble in water; practically insoluble in ethanol (95%); miscible with carbon disulfide, chloroform, ether, hexane, and light petroleum.

Specific rotation [a]25: +18 to +98

Viscosity (dynamic): 43 mPa s (43 cP)

Sesame Oil 647

Stability and Storage Conditions

Sesame oil is more stable than most other fixed oils and does not readily become rancid; this has been attributed to the antioxidant effect of some of its characteristic constituents. The PhEur 2005 permits the addition of a suitable antioxidant to sesame oil.

Sesame oil may be sterilized by aseptic filtration or dry heat. It has been reported that suitable conditions for the sterilization of injections containing sesame oil are a temperature of 1708C for 2 hours; it has been suggested that 1508C for 1 hour is inadequate.(15) However, it has been demonstrated that dry heat sterilization of sesame oil at 1508C for 1 hour was sufficient to kill all added Bacillus subtilis spores.(16)

Sesame oil should be stored in a well-filled, airtight, light- resistant container, at a temperature not exceeding 408C. Sesame oil intended for use in the manufacture of parenteral dosage forms should be stored under an inert gas in an airtight glass container.

Incompatibilities

Sesame oil may be saponified by alkali hydroxides.

Method of Manufacture

Sesame oil is obtained from the ripe seeds of one or more cultivated varieties of Sesamum indicum Linne´ (Fam. Pedalia- ceae) by expression in a hydraulic press or by solvent extraction. The crude oil thus obtained is refined to obtain an oil suitable for food or pharmaceutical use. Improved color and odor may be obtained by further refining.

Safety

Sesame oil is mainly used in intramuscular and subcutaneous injections; it should not be administered intravenously. It is also used in topical pharmaceutical formulations and consumed as an edible oil.

Although it is generally regarded as an essentially nontoxic and nonirritant material,(17) there have been rare reports of hypersensitivity to sesame oil, with sesamin suspected as being the primary allergen.(18–21) Anaphylactic reactions to sesame seeds have also been reported. However, it is thought that the allergens in the seeds may be inactivated or destroyed by heating as heat-extracted sesame seed oil or baked sesame seeds do not cause anaphylactic reactions in sesame seed-allergic individuals.(22)

LD50 (rabbit, IV): 678 mg/kg(23)

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Spillages of sesame oil are slippery and should be covered with an inert absorbent material prior to disposal.

Regulatory Status

Included in the FDA Inactive Ingredients Guide (IM and SC injections, oral capsules, emulsions, and tablets, also topical preparations). Included in parenteral (IM injections) and nonparenteral (oral capsules and sprays) medicines licensed in the UK. Included in the Canadian List of Acceptable Non- medicinal Ingredients.



Related Substances

Almond oil; canola oil; corn oil; cottonseed oil; peanut oil; soybean oil; sunflower oil.

Comments

—

Specific References

British Standards Institute. Specification for Crude Vegetable Fats, BS 7207. London: BSI, 1990.

Williams JS, Stein JH, Ferris TH. Nandrolone decanoate therapy for patients receiving hemodialysis. Arch Intern Med 1974; 134: 289–292.

Larsen SW, Rinvar E, Svendsen O, et al. Determination of the disappearance rate of iodine-125 labelled oils from the injection site after intramuscular and subcutaneous administration to pigs. Int J Pharm 2001; 230(1–2): 67–75.

Hirano K, Ichihashi T, Yamada H. Studies on the absorption of practically water-insoluble drugs following injection V: subcuta- neous absorption in rats from solutions in water immiscible oils. J Pharm Sci 1982; 71: 495–500.

Perez-Reyes M, Lipton MA, Timmons MC, et al. Pharmacology of orally administered ∆9-tetrahydrocannabinol. Clin Pharmacol Ther 1973; 14: 48–55.

Sallan SE, Zinberg NE, Frei E. Antiemetic effect of delta-9- tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 1975; 293: 795–797.

Tanabe K, Sawanoi M, Yamazaki M, Kamada A. Effect of different suppository bases on release of indomethacin [in Japanese]. Yakuzaigaku 1984; 44: 115–120.

Chien DS, Schoenwald RD. Ocular pharmacokinetics and pharmacodynamics of phenylephrine and phenylephrine oxazoli- dine in rabbit eyes. Pharm Res 1990; 7: 476–483.

Shinkuma D, Hamaguchi T, Muro C, et al. Bioavailability of phenytoin from oil suspension and emulsion in dogs. Int J Pharm 1981; 9: 17–28.

Rosenkrantz H, Thompson GR, Braude MC. Oral and parenteral formulations of marijuana constituents. J Pharm Sci 1972; 61: 1106–1112.

Unno K, Goto A, Kagaya S, et al. Preparation and tissue distribution of 5-fluorouracil emulsion [in Japanese]. J Nippon Hosp Pharm Assoc 1980; 6(1): 14–20.

Nakhare S, Vyas SP. Prolonged release of rifampicin from internal phase of multiple w/o/w emulsion systems. Indian J Pharm Sci 1995; 57(2): 71–77.

Rhee Y-S, Choi J-G, Park E-S, Chi S-C. Transdermal delivery of ketoprofen using microemulsions. Int J Pharm 2001; 228(1–2): 161–170.

Al-Achi A, Greenwood R, Akin-Isijola A, Bullard J. Calamine lotion: experimenting with a new suspending agent. Int J Pharm Compound 1999; 3(6): 490–492.

Pasquale D, Jaconia D, Eisman P, Lachman L. A study of sterilizing conditions for injectable oils. Bull Parenter Drug Assoc 1964; 18(3): 1–11.

Kupiec TC, Matthews P, Ahmad R. Dry-heat sterilisation of parenteral oil vehicles. Int J Pharm Compound 2000; 4(3): 223– 224.

Hem SL, Bright DR, Banker GS, Pogue JP. Tissue irritation evaluation of potential parenteral vehicles. Drug Dev Commun 1974–75 1: 471–477.

Neering H, Vitanyi BE, Malten KE, et al. Allergens in sesame oil contact dermatitis. Acta Dermatol Venerol 1975; 55: 31–34.

Weiner M, Bernstein IL. Adverse Reactions to Drug Formulation Agents: A Handbook of Excipients. New York: Marcel Dekker, 1989: 212–213.

Perkins MS. Sesame allergy is also a problem [letter]. Br Med J

1996; 313: 300.

Perkins MS. Raising awareness of sesame allergy. Pharm J 2001;

267: 757–758.

648 Sesame Oil

Ka¨ gi MK, Wu¨ thrich B. Falafel-burger anaphylaxis due to sesame seed allergy [letter]. Lancet 1991; 338: 582.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 3203.

General References

—

Authors

CG Cable.

Date of Revision

23 August 2005.

Shellac

Nonproprietary Names

BP: Shellac

JP: Purified shellac, White shellac PhEur: Lacca

USPNF: Shellac

Synonyms

Bleached shellac; CertiSeal; dewaxed orange shellac; E904; lac; Mantrolac R-49; orange shellac; refined bleached shellac; regular bleached shellac; Swanlac.

Chemical Name and CAS Registry Number

Shellac [9000-59-3]

Empirical Formula and Molecular Weight

Shellac is a naturally occurring material consisting of a complex mixture of constituents that may be obtained in various refined or modified forms; see Section 13.

The PhEur 2005 defines four types of shellac depending on the nature of the treatment of the crude shellac (seed lac): wax- containing shellac; bleached shellac; dewaxed shellac; and bleached dewaxed shellac. The USPNF 23 similarly defines four types of shellac: orange shellac; dewaxed orange shellac; regular bleached (white) shellac; and refined bleached shellac. The JP 2001 defines two types: purified shellac and white shellac (bleached).

Elementary analysis reveals that shellac contains carbon, hydrogen, oxygen, and a negligible amount of ash. A formula of C60H90O15 and an average molecular weight of 1000 is assigned to shellac. Although its composition has not been fully elucidated, the main component of shellac (about 95%) is a resin that gives a mixture of aliphatic and alicyclic hydroxy acids and polyesters on mild basic hydrolysis. Some of the compounds identified and named include aleuritic, butolic, kerrolic, and shellolic acids. The major component of the aliphatic fraction is aleuritic acid, while the major component of the alicyclic fraction is shellolic acid.

Shellac also contains about 5–6% wax along with gluten, other impurities, and a small amount of pigment. The exact composition of shellac may vary depending upon the country of origin and method of manufacture.(1,2)

Structural Formula

See Section 4.

Functional Category

Coating agent.

Applications in Pharmaceutical Formulation or Technology

Shellac has been used in pharmaceutical formulations for the enteric coating of tablets and beads,(3) the material usually

being applied as a 35% w/v alcoholic solution; see also Section 18.

It is a primary ingredient of pharmaceutical printing inks for monogramming capsules and tablets, and can be applied as a 40% w/v alcoholic solution. It has also been used to apply one or two sealing coats to tablet cores to protect them from moisture before being film- or sugar-coated.

Shellac may also be used in food products and cosmetics.

Description

Shellac is a naturally occurring material that may be obtained in a variety of refined or modified forms; see Sections 4 and 13.

Generally, shellac occurs as hard, brittle, transparent, pale lemon-yellow to brownish orange-colored flakes of varying size and shape; it is also available as a powder. Shellac is tasteless and odorless, or may have a faint odor.

Pharmacopeial Specifications

See Table I.

Table I:  Pharmacopeial specifications for shellac.

 

Test JP 2001 PhEur 2005 USPNF 23    

Identification — + +    

Characters — + —    

Heavy metals 410 ppm 410 ppm 40.001%    

Arsenic 45 ppm 43 ppm —    

Ethanol-insoluble substances 42.0% — —    

Rosin + — +    

Total ash 41.0% — —    

Acid value (on dried basis) 60–80 65–95 +    

Dewaxed orange shellac — — 71–79    

Orange shellac — — 68–76    

Refined bleached shellac — — 75–91    

Regular bleached shellac — — 73–89    

Loss on drying 42.0% + +    

Dewaxed orange shellac — — 42.0%    

Orange shellac — — 42.0%    

Refined bleached shellac — — 46.0%    

Regular bleached shellac — 46.0% 46.0%    

Unbleached shellac — 42.0% —    

Wax 420 mg — +  

Dewaxed orange shellac  — — 40.2% Orange shellac — — 45.5% Refined bleached shellac  — — 40.2% Regular bleached shellac  — — 45.5%

Typical Properties

Alcohol-insoluble matter: 41.0%

Ash: 41.0%

Density: 1.035–1.140 g/cm3

Hydroxyl value: 230–280

Iodine number: 10–18

Melting point: 115–1208C

650 Shellac

Refractive index: n20 = 1.5210–1.5272 Saponification value: 185–210 Solubility: see Table II.

Table II: Solubility of shellac.

Solvent Solubility at 208C

Alkalis Soluble

Aqueous ethanolamine solution Soluble Benzene 1 in 10

Ethanol 1 in 2

Ethanol (95%) 1 in 1.2 (very slowly soluble)

Ether 1 in 8

Hexane Practically insoluble

Propylene glycol 1 in 10

Water Practically insoluble

Stability and Storage Conditions

After long periods of storage, shellac becomes less readily soluble in alcohol, less fluid on heating, and darker in color. Shellac-coated tablets may have increased disintegration times following prolonged storage owing to changes in the physical characteristics of the coating; see Section 18.(4)

Shellac should be stored in a well-closed container at temperatures below 278C. Wax-containing grades should be mixed before use to ensure uniform distribution of the wax.