Aspartame Excipient | Uses, Suppliers, and Specifications
Aspartame is a synthetic, non-carbohydrate sweetener (high-intensity sweetener) that can be chemically described as the methyl ester of the dipeptide of two amino acids: aspartic acid, and phenylalanine. It has an approximate sweetness that is 180-200 times that of Sucrose. Aspartame is supplied as an off-white, almost odourless crystalline powder with an intensely sweet taste.
Synonyms and Trade Names: Aspartame; 3-amino-N-(α-carboxyphenethyl)succinamic acid; N-methyl ester methyl N-L-a-aspartyl-L-phenylalaninate; 3-amino-N-(α-methoxycarbonyIphenethyl) succinamic acid; (3S)-3-Amino-4-l [(1S)-1 -beiszyl-2-methoxy-2-oxoethyl)aminoj-4- oxobutanoic acid; APM; E951; Canderel; Equal; NatraTaste; NutraSweet; Pal Sweet; Sanecta; SC1 8862; Tri-Sweet
Pharmacopoeial Compliance: USP-NF; Ph. Eur; JP; IP; FCC
Uses and Applications: Intense Sweetening Agent
Aspartame is the name for a synthetic, non-carbohydrate sweetener, known by the chemical name aspartyl-phenylalanine-1-methyl ester. It is sold under various trade names, including EQUAL®, NutraSweet® and Canderel® and is approximately 200 times sweeter than Sucrose.
Formally, Aspartame is a condensation product of two naturally-occurring amino acids, aspartic acid and phenylalanine linked by an amide bond. The synthetic process proceeds via two steps:
- The first step involves the production of the two amino acids by fermentation using a suitable bacterial culture. The fermentation conditions require the addition of suitable carbon and nitrogen sources.
- The second step is a multistep chemical synthetic pathway in which the two amino acids are combined to produce aspartyl-phenylalanine-1-methyl ester.
Aspartame was serendipitously discovered by Jim Schlatter in 1965, a scientist at G.D.Searle (now part of Pfizer). The story goes that he had synthesised aspartyl-phenylalanine methyl ester as an intermediate for a new anti-ulcer-drug programme. He inadvertently got some of the substance on his hand and when he later licked his finger noticed that it was intensely sweet. His supervisor, Bob Mazur, realising the potential benefits of the new finding, embarked on further studies to demonstrate the safety of Aspartame. It would take almost a decade before Aspartame became approved for use in foods by the US FDA.
Aspartame is a highly attractive artificial sweetener because it is considered to best mimic the qualities of Sucrose in terms of flavour, taste duration, and minimal aftertaste when compared to other artificial sweeteners. However, it has been mired in controversies regarding its safety. Despite these concerns and multiple studies over the past four decades, no substantive evidence of adverse effects both in controlled and non-controlled studies has emerged.
Pharmaceutical-grade Aspartame is supplied as an off white, almost odourless crystalline powder with an intensely sweet taste.
Chemical Structure & Identifiers
|Chemical Name||N-L-α-Aspartyl-L- phenylalanine 1-methyl ester|
|CAS Registry Number||[22839-47-0]|
|Molecular Weight||294.30 g/mol|
|UNII Code (FDA)||Z0H242BBR1|
Aspartame is listed in all three main pharmacopoeias (USP-NF; Ph.Eur and JP). It is also FDA approved as a food additive in the United States and included in the Inactive Ingredients Database (covering tablets, oral powders for reconstitution, buccal patches, granules, and syrups). It is similarly approved in the European Union as a food additive (E951) and excipient. A specification for aspartame is contained in the Food Chemicals Codex (FCC).
|Appearance||White or off-white crystalline powder|
|pH||pH = 4.5-6.0 (0.8% w/v aqueous solution)|
|Brittle fracture index||1.05|
|Bonding index||0.8 – 2.3 x 102|
|Flowability||44% (Carr compressibility index)|
|Bulk density||0.1 – 0.7 g/ml (dependent on grade)|
|Tapped Density||0.2 – 0.3 g/ml (dependent on grade)|
|True Density||1.347 g/ml|
|Effective angle of internal friction||43.0o|
|Melting point||246-247 oC|
|Solubility||Water solubility is dependent on pH and temperature. Maximum solubility is achieved at pH 2.2-5.2, which varies between 20 mg/ml and 13.5 mg/ml at 25 °C|
|Specific rotation||+14.5o – +16.5o|
|Appearance of solution||n/a||specified|
|Specific optical rotation||+14.50 to 16.50||+14.50 to 16.50|
|Heavy metals||≤ 0.001%||≤ 10 ppm|
|Loss on drying||4.5%||≤ 4.5%|
|Residue on ignition||≤ 0.2%||n/a|
|Sulfated ash||n/a||≤ 0.2%|
|Limit of 5 –benzyl n/a3, 6n/adioxon/a2n/apiperazineacetic acid||≤ 1.5%||n/a|
|Assay||98.0 – 102.0%||98.0 – 102.0%|
Key: n/a Specification is not listed
*All claims with respect to conformity are subject to our Terms and Conditions. No express or implied warranty is made for specific properties or fitness for any particular application or purpose.
Applications in Pharmaceutical Formulations or Technology
Aspartame is a high-intensity sweetener with an approximate sweetness which is 180-200 times that of Sucrose. It is used widely as an intense sweetening agent in the food industry (beverages, food products and table-top sweeteners). Since solubility and stability are most optimum at pH 4.3, Aspartame is widely added to carbonated beverages. Aspartame has a caloric value of 4 kcal/g. However, the quantity required to achieve sweetness is very small thus the caloric contribution is negligible.
Within the pharmaceutical field, Aspartame is used in tablets, powder mixes and nutraceutical formulations. It is used to enhance flavours and can also aid in the masking of unpleasant tastes. Aspartame has a slower onset and longer duration than that sugar, which can be somewhat unappealing for some products. For this reason, Aspartame is frequently used in combination with Acesulfame Potassium.
Being peptides, Aspartame can hydrolise into its constituent amino acids under conditions of elevated temperature or high pH. This makes aspartame undesirable in processes that utilise heat or formulations that have a high pH. Thermal stability can be improved by trapping Aspartame in Maltodextrin.
Aqueous stability is most optimum at pH 4.3, where its half-life of approximately 300 days. At pH 7, the half-life is only a matter of days. In products that require a longer shelf life, Aspartame can be blended or substituted with more stable sweeteners, such as Saccharin.
Finally, in powdered products, the amine group in Aspartame can undergo a Maillard reaction upon contact with aldehydes found in sugars or flavour compounds.
Safety and Precautions
Aspartame is approved for use in oral pharmaceutical formulations, beverages, and food products as an intense sweetener, and is generally regarded as a nontoxic material. However, unlike some other intense sweeteners, it undergoes metabolism in the body and consequently has some nutritive value: 1g provides approximately 17 kJ (4kcal). In practice, the small quantities of aspartame consumed mean that the nutritive effect is minimal.
Also, there have been concerns with aspartame due to the formation of the potentially toxic metabolites: methanol, aspartic acid, and phenylalanine. These have been extensively investigated for a period spanning three decades, including experimental animal studies, clinical research, intake and epidemiological studies and post-marketing surveillance, and found to be safe. Aspartame has previously been evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the EU Scientific Committee for Food (SCF) and the European Food Safety Authority (EFSA). Both JECFA and SCF established an Acceptable Daily Intake (ADI) of 40 mg/kg body weight (bw)/day.
However, some adverse effects (headaches, grand mal seizure, memory loss, gastrointestinal symptoms; and dermatological symptoms) have been reported following the consumption of Aspartame, e.g individuals who drink large quantities of beverages sweetened with Aspartame. Other controlled studies showed Aspartame to be safe with no credible link between consumption at standard levels and symptoms.
Reports of hyperactivity and behavioural problems in children have also not been substantiated. For instance, a controlled trial of over 4o preschool-age children (fed diets containing a daily intake of 38 ± 13mg/kg body-weight of Aspartame for 21 days) no link between Aspartame and the children’s behavioural or cognitive functions could be found. To date, there is also no reliable evidence that Aspartame is carcinogenic.
Stability and Storage Conditions
Aspartame is reported to be a stable excipient under dry conditions. The assigned shelf life is 24-36 months. However, when exposed to moisture, hydrolysis may occur forming L-aspartyl-L- phenylalanine, 3-benzyl-6-carboxymethyl-2,5-diketopiperazine, and β-aspartyl-L-phenylalanine methyl ester, followed by a loss of functionality. A third-degradation product is also known. For this reason, the material should be stored in a well-closed container, in a cool, dry place.
Aspartame degradation can also occur upon prolonged exposure to heat. Degradation can be reduced by employing processes that utilise high temperatures for short time followed by rapid cooling.
When processing Aspartame, observe relevant SHEQ precautions appropriate to the circumstances and quantity of material being handled. Any potential for dust generation should be minimised. PPE is recommended.
Sustainability and Environmental Impact
A sustainability score for Aspartame has not been undertaken.
Manufacturers & Suppliers
Ajinomoto Co. Inc
HSWT France SAS
Vitasweet Co. Ltd
Additional Resources (Downloads)
References and Literature Used
 H.H. Butchko, W.W. Stargel, C.P. Comer, D.A. Mayhew, C. Benninger, G.L. Blackburn, L.M.J. de Sonneville, R.S. Geha, Z. Hertelendy, A. Koestner, Aspartame: review of safety, Regulatory Toxicology and Pharmacology, 35 (2002) S1-S93.
 S.D. Anton, C.K. Martin, H. Han, S. Coulon, W.T. Cefalu, P. Geiselman, D.A. Williamson, Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels, Appetite, 55 (2010) 37-43.
 S. Arora, A.M. Shendurse, V. Sharma, B.K. Wadhwa, A.K. Singh, Assessment of stability of binary sweetener blend (aspartame x acesulfame-K) during storage in whey lemon beverage, Journal of Food Science and Technology, 50 (2013) 770-776.
 Food Chemicals Codex, 12th edn. Bethesda, MD: United States.
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