Name: Aspartame
CAS No: N-L-a-Aspartyl-L-phenylalanine 1-methyl ester [22839-47-0]
BP: Aspartame PhEur: Aspartame USP-NF: Aspartame
(3S)-3-Amino-4-[[(1S)-1-benzyl-2-methoxy-2-oxoethyl]amino]-4- oxobutanoic acid; 3-amino-N-(a-carboxyphenethyl)succinamic acid N-methyl ester; 3-amino-N-(a-methoxycarbonylphenethyl)- succinamic acid; APM; aspartamum; aspartyl phenylamine methyl ester; Canderel; E951; Equal; methyl N-L-a-aspartyl-L-phenylalaninate; NatraTaste; NutraSweet; Pal Sweet; Pal Sweet Diet; Sanecta; SC-18862; Tri-Sweet.
N-L-a-Aspartyl-L-phenylalanine 1-methyl ester [22839-47-0]
C14H18N2O5 294.30
Aspartame is used as an intense sweetening agent in beverage products, food products, and table-top sweeteners, and in pharmaceutical preparations including tablets,(1,2) powder mixes, and vitamin preparations. It enhances flavor systems and can be used to mask some unpleasant taste characteristics; the approximate sweetening power is 180–200 times that of sucrose. Unlike some other intense sweeteners, aspartame is metabolized in the body and consequently has some nutritive value: 1 g provides approximately 17 kJ (4 kcal). However, in practice, the small quantity of aspartame consumed provides a minimal nutritive effect.
Aspartame occurs as an off white, almost odorless crystalline powder with an intensely sweet taste.
See Table I.
Acidity/alkalinity pH = 4.5–6.0 (0.8% w/v aqueous solution) Brittle fracture index 1.05(3) Bonding index 0.8 102 (worst case)(3) 2.3 102 (best case)(3) Flowability 44% (Carr compressibility index)(3) Density (bulk) 0.5–0.7 g/cm3 for granular grade; 0.2–0.4 g/cm3 for powder grade; 0.17 g/cm3 (Spectrum Quality Products).(3) Density (tapped) 0.29 g/cm3 (Spectrum Quality Products)(3) Density (true) 1.347 g/cm3 Effective angle of internal friction 43.08 (3) Melting point 246–2478C NIR spectra see Figure 1. Solubility Slightly soluble in ethanol (95%); sparingly soluble in water. At 208C the solubility is 1% w/v at the isoelectric point (pH 5.2). Solubility increases at higher temperature and at more acidic pH, e.g., at pH 2 and 208C solubility is 10% w/v. Specific rotation [a]D 22 = 2.38 in 1 N HCl
Aspartame is stable in dry conditions. In the presence of moisture, hydrolysis occurs to form the degradation products L -aspartyl-Lphenylalanine and 3-benzyl-6-carboxymethyl-2,5-diketopiperazine with a resulting loss of sweetness. A third-degradation product is also known, b-L-aspartyl-L-phenylalanine methyl ester. For the stability profile at 258C in aqueous buffers, see Figure 2. Stability in aqueous solutions has been enhanced by the addition of cyclodextrins,(4,5) and by the addition of polyethylene glycol 400 at pH 2.(6) However, at pH 3.5–4.5 stability is not enhanced by the replacement of water with organic solvents.(7) Aspartame degradation also occurs during prolonged heat treatment; losses of aspartame may be minimized by using processes that employ high temperatures for a short time followed by rapid cooling. The bulk material should be stored in a well-closed container, in a cool, dry place.
Differential scanning calorimetry experiments with some directly compressible tablet excipients suggests that aspartame is incompatible with dibasic calcium phosphate and also with the lubricant magnesium stearate.(9) Reactions between aspartame and sugar alcohols are also known.
Aspartame is produced by coupling together L-phenylalanine (or Lphenylalanine methyl ester) and L-aspartic acid, either chemically or enzymatically. The former procedure yields both the sweet aaspartame and nonsweet b-aspartame from which the a-aspartame has to be separated and purified. The enzymatic process yields only a-aspartame.
Aspartame is widely used in oral pharmaceutical formulations, beverages, and food products as an intense sweetener, and is generally regarded as a nontoxic material. However, the use of aspartame has been of some concern owing to the formation of the potentially toxic metabolites methanol, aspartic acid, and phenylalanine. Of these materials, only phenylalanine is produced in sufficient quantities, at normal aspartame intake levels, to cause concern. In the normal healthy individual any phenylalanine produced is harmless; however, it is recommended that aspartame be avoided or its intake restricted by those persons with phenylketonuria.(10) The WHO has set an acceptable daily intake for aspartame at up to 40 mg/kg body-weight.(11) Additionally, the acceptable daily intake of diketopiperazine (an impurity found in aspartame) has been set by the WHO at up to 7.5 mg/kg body-weight.(12) A number of adverse effects have been reported following the consumption of aspartame,(10,12) particularly in individuals who drink large quantities (up to 8 liters per day in one case) of aspartame-sweetened beverages. Reported adverse effects include: headaches;(13) grand mal seizure;(14) memory loss;(15) gastrointestinal symptoms; and dermatological symptoms. However, scientifically controlled peer-reviewed studies have consistently failed to produce evidence of a causal effect between aspartame consumption and adverse health events.(16,17) Controlled and thorough studies have confirmed aspartame’s safety and found no credible link between consumption of aspartame at levels found in the human diet and conditions related to the nervous system and behavior, nor any other symptom or illness. Aspartame is well documented to be nongenotoxic and there is no credible evidence that aspartame is carcinogenic.(18) Although aspartame has been reported to cause hyperactivity and behavioral problems in children, a double-blind controlled trial of 48 preschool-age children fed diets containing a daily intake of 38 13 mg/kg body-weight of aspartame for 3 weeks showed no adverse effects attributable to aspartame, or dietary sucrose, on children’s behavior or cognitive function.(19)
Observe normal precautions appropriate to the circumstances and quantity of material handled. Measures should be taken to minimize the potential for dust explosion. Eye protection is recommended.
Accepted for use as a food additive in Europe and in the USA. Included in the FDA Inactive Ingredients Database (oral powder for reconstitution, buccal patch, granules, syrups, and tablets). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients
Alitame; aspartame acesulfame; neotame. Aspartame acesulfame Empirical formula C18H23O9N3S Molecular weight 457.46 CAS number 106372-55-8 Comments A compound of aspartame and acesulfame approx. 350 times sweeter than sucrose. Aspartame acesulfame is listed in the USP32–NF27.
The 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. Intense sweetening agents will not replace the bulk, textural, or preservative characteristics of sugar, if sugar is removed from a formulation. Synergistic effects for combinations of sweeteners have been reported, e.g. aspartame with acesulfame potassium. Aspartame can cause browning when used at high temperatures. A specification for aspartame is contained in the Food Chemicals Codex (FCC).(20) The PubChem Compound ID (CID) for aspartame includes 2242 and 21462246.