Holte O, Onsoven E, Myrvold R. Sustained release of water- soluble drug from directly compressed alginate tablets. Eur J Pharm Sci 2003; 20(4–5): 403–407.

Azarmi S, Valizadeh H, Barzegar JM, Loebenberg R. ’In situ’ cross- linking of polyanionic polymers to sustain the drug-release of acetazolamide tablets. Pharm Ind 2003; 63(9): 877–881.

Veski P, Marvola M, Smal J, et al. Biopharmaceutical evaluation of pseudoephedrine hydrochloride capsules containing different grades of sodium alginate. Int J Pharm 1994; 111: 171–179.

Zatz JL, Woodford DW. Prolonged release of theophylline from aqueous suspensions. Drug Dev Ind Pharm 1987; 13: 2159–2178.

Bodmeier R, Wang J. Microencapsulation of drugs with aqueous colloidal polymer dispersions. J Pharm Sci 1993; 82: 191–194.

Rajaonarivony M, Vauthier C, Couarraze G, et al. Development of a new drug carrier made from alginate. J Pharm Sci 1993; 82(9): 912–917.

Vennat B, Lardy F, Arvouet-Grand A, Pourrat A. Comparative texturometric analysis of hydrogels based on cellulose derivatives, carraghenates, and alginates: evaluation of adhesiveness. Drug Dev Ind Pharm 1998; 24(1): 27–35.

Miyazaki S, Nakayama A, Oda M, et al. Drug release from oral mucosal adhesive tablets of chitosan and sodium alginate. Int J Pharm 1995; 118: 257–263.

Attia MA, ElGibaly I, Slialtout SE. Transbuccal permeation, anti- inflammatory and clinical efficacy of piroxicam formulated in different gels. Int J Pharm 2004; 276: 11–28.

Mohammed FA, Kheder H. Preparation and in vitro/in vivo evaluations of the buccal bioadhesive properties of slow-release tablets containing miconazole nitrate. Drug Dev Ind Pharm 2003; 29(3): 321–337.

Cohen S, Lobel E, Trevgoda A, Peled Y. A novel in situ-forming ophthalmic drug delivery system from alginates undergoing gelation in the eye. J Control Release 1997; 44: 201–208.

Balasubramaniam J, Pandit JK. Ion-activated in situ gelling systems for sustained release ophthalmic delivery of ciprofloxacin hydrochloride. Drug Delivery 2003; 10(3): 185–191.

Kubo W, Miyazaki S, Attwood D. Oral sustained delivery of paracetamol from in-situ gelling gellan and sodium alginate formulations. Int J Pharm 2003; 258(1–2): 55–64.

Duggirala S, DeLuca PP. Buffer uptake and mass loss character- istics of freeze-dried cellulosic and alginate devices. PDA J Pharm Sci Technol 1996; 50(5): 297–305.

Gombotz WR, Pettit DK. Biodegradable polymers for protein and peptide drug delivery. Bioconjug Chem 1995; 6: 332–351.

Stanciu C, Bennett JR. Alginate/antacid in the reduction of gastro- oesophageal reflux. Lancet 1974; i: 109–111.

Thomas S. Wound Management and Dressings. London: Pharma- ceutical Press, 1990: 43–49.

Qin Y, Gilding DK. Alginate fibres and wound dressings. Med Device Technol 1996; Nov: 32–41.

Thomas S. Alginate dressings in surgery and wound manage- ment—Part 1. J Wound Care 2000; 9(2): 56–60.

Lai HL, Abu Khalil A, Craig DQM. The preparation and characteristics of drug-loaded alginate and chitosan sponges. Int J Pharm 2003; 251: 175–181.

Bugaj J, Go´ recki M. Kinetics of dynamic viscosity changes of aqueous sodium carboxymethylcellulose and sodium alginate solutions. Pharmazie 1995; 50(11): 750–752.

Duggirala S, DeLuca PP. Rheological characterization of cellulosic and alginate polymers. PDA J Pharm Sci Technol 1996; 50(5): 290–296.

Bugaj J, Go´ recki M. Rheometrical estimation of physical proper- ties of sodium alginate and sodium carboxymethylcellulose aqueous solutions. Acta Pol Pharm Drug Res 1996; 53(2): 141– 146.

Pa´vics L. Comparison of rheological properties of mucilages [in Hungarian]. Acta Pharm Hung 1970; 40: 52–59.

Coates D, Richardson G. A note on the production of sterile solutions of sodium alginate. Can J Pharm Sci 1974; 9: 60–61.

Vandenbossche GMR, Remon J-P. Influence of the sterilization process on alginate dispersions. J Pharm Pharmacol 1993; 45: 484–486.

Hartman AW, Nesbitt RU, Smith FM, Nuessle NO. Viscosities of acacia and sodium alginate after sterilization by cobalt-60. J Pharm Sci 1975; 64: 802–805.

Anderson DM, Brydon WG, Eastwood MA, Sedgwick DM. Dietary effects of sodium alginate in humans. Food Addit Contam 1991; 8(3): 237–248.

FAO/WHO. Evaluation of certain food additives and naturally occurring toxicants. Thirty-ninth report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1992; No. 828.

Henderson AK, Ranger AF, Lloyd J, et al. Pulmonary hypersensi- tivity in the alginate industry. Scott Med J 1984; 29(2): 90–95.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 3225–3226.

General References

—

Authors

CG Cable.

Date of Revision

20 August 2005.

Sodium Ascorbate

Nonproprietary Names

PhEur: Natrii ascorbas USP: Sodium ascorbate

Synonyms

L-Ascorbic acid monosodium salt; E301; 3-oxo-L-gulofurano- lactone sodium enolate; SA-99; vitamin C sodium.

Chemical Name and CAS Registry Number

Monosodium L-(+)-ascorbate [134-03-2]

Empirical Formula and Molecular Weight

C6H7NaO6 198.11

Structural Formula

 

Functional Category

Antioxidant; therapeutic agent.

Applications in Pharmaceutical Formulation or Technology

Sodium ascorbate is used as an antioxidant in pharmaceutical formulations, and also in food products where it increases the effectiveness of sodium nitrite against growth of Listeria monocytogenes in cooked meats. It improves gel cohesiveness and sensory firmness of fiberized products regardless of vacuum treatment.

It is also used therapeutically as a source of vitamin C in tablets and parenteral preparations.

Description

Sodium ascorbate occurs as a white or slightly yellow-colored, practically odorless, crystalline powder with a pleasant saline taste.

SEM: 1

Excipient: Sodium ascorbate USP

Manufacturer: Pfizer Ltd.

Lot No: 9B-1 (C92220-C4025)

Magnification: 120×

Voltage: 20 kV

 

SEM: 2

Excipient: Sodium ascorbate USP

Manufacturer: Pfizer Ltd.

Lot No: 9B-1 (C92220-C4025)

Magnification: 600×

Voltage: 20 kV

 

660 Sodium Ascorbate

Pharmacopeial Specifications

See Table I.

Table I:  Pharmacopeial specifications for sodium ascorbate.

 

Test PhEur 2005 USP 28    

Identification + +    

Characters + —    

Appearance of solution + —    

pH 7.0–8.0 7.0–8.0    

Specific optical rotation +1038 to +1088 +1038 to +1088    

(10% w/v aqueous solution)    

Oxalic acid 40.30% —    

Benzene 42 ppm —    

Sulfates 4150 ppm —    

Copper 45 ppm —    

Iron 42 ppm —    

Nickel 41 ppm —    

Heavy metals 410 ppm 40.002%    

Loss on drying 40.25% 40.25%    

Organic volatile impurities — +    

Assay (dried basis) 99.0–101.0% 99.0–101.0%  

Typical Properties

Acidity/alkalinity: pH = 7–8 (10% w/v aqueous solution)

Density (tapped):

0.6–1.1 g/cm3 for fine powder; 0.8–1.1 g/cm3 for fine granular grade.

Density (true): 1.826 g/cm3

Hygroscopicity: not hygroscopic. Sodium ascorbate adsorbs practically no water up to 80% relative humidity at 208C and less than 1% w/w of water at 90% relative humidity.

Melting point: 2188C (with decomposition)

Particle size distribution: various grades of sodium ascorbate with different particle-size distributions are commercially available, e.g., approximately 98% passes through a 149 mm mesh for a fine powder grade (Takeda), and approximately 95% passes through a 840 mm mesh for a standard grade (Takeda).

Solubility: see Table II.

Table II: Solubility of sodium ascorbate.

The bulk material should be stored in a well-closed nonmetallic container, protected from light, in a cool, dry place.

Incompatibilities

Incompatible with oxidizing agents, heavy metal ions, espe- cially copper and iron, methenamine, sodium nitrite, sodium salicylate, and theobromine salicylate. The aqueous solution is reported to be incompatible with stainless steel filters.(1)

Method of Manufacture

An equivalent amount of sodium bicarbonate is added to a solution of ascorbic acid in water. Following the cessation of effervescence, the addition of propan-2-ol precipitates sodium ascorbate.

Safety

The parenteral administration of 0.25—1.00 g of sodium ascorbate, given daily in divided doses, is recommended in the treatment of vitamin C deficiencies. Various adverse reactions have been reported following the administration of 1 g or more of sodium ascorbate, although ascorbic acid and sodium ascorbate are usually well tolerated; see Ascorbic acid. There have been no reports of adverse effects associated with the much lower concentrations of sodium ascorbate and ascorbic acid, which are employed as antioxidants.

The WHO has set an acceptable daily intake of ascorbic acid, potassium ascorbate, and sodium ascorbate, as antiox- idants in food, at up to 15 mg/kg body-weight in addition to that naturally present in food.(2)

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Sodium ascorbate may be irritant to the eyes. Eye protection and rubber or plastic gloves are recommended.

Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Guide (IV prepara- tions; oral tablets). Included in nonparenteral and parenteral

medicines licensed in the UK. Included in the Canadian List of

Solvent Solubility at 208C unless otherwise stated

Chloroform Practically insoluble

Ethanol (95%) Very slightly soluble

Ether Practically insoluble

Water 1 in 1.6

1 in 1.3 at 758C

Specific gravity:

1.782 for powder at 208C;

1.005 for 1% w/v aqueous solution at 258C;

1.026 for 5% w/v aqueous solution at 258C.

Specific rotation [a]20: +104.48(10% w/v aqueous solution)

Stability and Storage Conditions

Sodium ascorbate is relatively stable in air, although it gradually darkens on exposure to light. Aqueous solutions are unstable and subject to rapid oxidation in air at pH > 6.0.

Acceptable Non-medicinal Ingredients.

Related Substances

Ascorbic acid; ascorbyl palmitate; calcium ascorbate.

Calcium ascorbate

Empirical formula: C12H14O12Ca

Molecular weight: 390.31

CAS number: [5743-27-1]

Synonyms: calcium L-(+)-ascorbate; CCal-97; E302.

Comments

1 mg of sodium ascorbate is equivalent to 0.8890 mg of ascorbic acid (1 mg of ascorbic acid is equivalent to 1.1248 mg of sodium ascorbate); 1 g of sodium ascorbate contains approximately 5 mmol of sodium. A specification for sodium ascorbate is contained in the Food Chemicals Codex (FCC).

The EINECS number for sodium ascorbate is 205-126-1.

Sodium Ascorbate 661

Specific References

Buck GW, Wolfe KR. Interaction of sodium ascorbate with stainless steel particulate filter needles [letter]. Am J Hosp Pharm 1991; 48: 1191.

FAO/WHO. Toxicological evaluation of certain food additives with a review of general principles and of specifications. Seventeenth report of the FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1974; No. 539.

General References

Dahl GB, Jeppsson RI, Tengborn HJ. Vitamin stability in a TPN mixture stored in an EVA plastic bag. J Clin Hosp Pharm 1986; 11: 271–279.

DeRitter E, Magid L, Osadca M, Rubin SH. Effect of silica gel on stability and biological availability of ascorbic acid. J Pharm Sci 1970; 59: 229–232.

Dettman IC. Sterilization of ascorbates by heat and absolute ethanol.

United States Patent No. 4,816,223; 1989.



Iida S, Kita K, Ootsuki H. Stable ascorbic acid solutions. Japanese Patent No. 61,130,205; 1986.

Kitamori N, Hemmi K, Maeno M, Mima H. Direct compression of chewable vitamin C tablets. Pharm Technol 1982; 6(10): 56–64.

Pfeifer HJ, Webb JW. Compatibility of penicillin and ascorbic acid injection. Am J Hosp Pharm 1976; 33: 448–450.

Sekine K, Araki D, Suzuki Y. Powdery pharmaceutical compositions containing ascorbic acids for intranasal administration. Japanese Patent No. 63,115,820; 1988.

Thielemann AM, Arata R, Morasso MI, Arancibia A. Biopharmaceu- tical study of a vitamin C controlled-release formulation. Farmaco (Prat) 1988; 43: 387–395.

Authors

CP McCoy.

Date of Revision

17 August 2005.

Sodium Benzoate

Nonproprietary Names

BP: Sodium benzoate JP: Sodium benzoate PhEur: Natrii benzoas

USPNF : Sodium benzoate

Synonyms

Benzoic acid sodium salt; benzoate of soda; E211; natrium benzoicum; sobenate; sodii benzoas; sodium benzoic acid.

Chemical Name and CAS Registry Number

Sodium benzoate [532-32-1]

Empirical Formula and Molecular Weight

C7H5NaO2 144.11

Structural Formula

 

Functional Category

Antimicrobial preservative; tablet and capsule lubricant.

Applications in Pharmaceutical Formulation or Technology

Sodium benzoate is used primarily as an antimicrobial preservative in cosmetics, foods, and pharmaceuticals. It is used in concentrations of 0.02–0.5% in oral medicines, 0.5% in parenteral products, and 0.1–0.5% in cosmetics. The useful- ness of sodium benzoate as a preservative is limited by its effectiveness over a narrow pH range; see Section 10.

Sodium benzoate is used in preference to benzoic acid in some circumstances, owing to its greater solubility. However, in some applications it may impart an unpleasant flavor to a product. Sodium benzoate has also been used as a tablet lubricant(1) at 2–5% w/w concentrations. Solutions of sodium benzoate have also been administered, orally or intravenously, in order to determine liver function.

Description

Sodium benzoate occurs as a white granular or crystalline, slightly hygroscopic powder. It is odorless, or with faint odor of benzoin and has an unpleasant sweet and saline taste.

SEM: 1

Excipient: Sodium benzoate Manufacturer: Bush Boake Allen Corp. Magnification: 60×

 

SEM: 2

Excipient: Sodium benzoate Manufacturer: Bush Boake Allen Corp. Magnification: 2400×

 

Pharmacopeial Specifications

See Table I.

Sodium Benzoate 663

Table I: Pharmacopeial specifications for sodium benzoate.

 

Test JP 2001 PhEur 2005 USPNF 23    

Identification + + +    

Characters + + —    

Acidity or alkalinity + + +    

Appearance of solution + + —    

Arsenic 42 ppm — —    

Chloride + 4200 ppm —    

Heavy metals 420 ppm 410 ppm 40.001%    

Organic volatile — — +    

impurities    

Loss on drying 41.5% 42.0% 41.5%    

Phthalic acid + — —    

Sulfate 40.120% — —    

Total chlorine — 4300 ppm —    

Assay (dried basis) 599.0% 99.0–100.5% 99.0–100.5%  

Typical Properties

Acidity/alkalinity: pH = 8.0 (saturated aqueous solution at 258C). It is relatively inactive above approximately pH 5.

Antimicrobial activity: sodium benzoate has both bacteriostatic and antifungal properties attributed to undissociated benzoic acid, hence preservative efficacy is best seen in acidic solutions (pH 2–5). In alkaline conditions it is almost without effect.

Density: 1.497–1.527 g/cm3 at 248C

Freezing point depression: 0.248C (1.0% w/v)

Osmolarity: a 2.25% w/v aqueous solution is iso-osmotic with serum.

Partition coefficients:

Vegetable oil : water = 3–6

Solubility: see Table II.

Table II: Solubility for sodium benzoate.

Solvent Solubility at 208C unless otherwise stated

Ethanol (95%) 1 in 75

Ethanol (90%) 1 in 50

Water 1 in 1.8

1 in 1.4 at 1008C

Stability and Storage Conditions

Aqueous solutions may be sterilized by autoclaving or filtration.

The bulk material should be stored in a well-closed container, in a cool, dry place.

Incompatibilities

Incompatible with quaternary compounds, gelatin, ferric salts, calcium salts, and salts of heavy metals, including silver, lead, and mercury. Preservative activity may be reduced by interac- tions with kaolin(2) or nonionic surfactants.

Method of Manufacture

Prepared by the treatment of benzoic acid with either sodium carbonate or sodium bicarbonate.