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Sorbitol Excipient | Uses, Suppliers, and Specifications
Sorbitol (chemical name: O-glucitol) is a hexahydric alcohol (polyol) related to mannose and isomeric with mannitol (chemical formula C6H8(OH)6). It occurs naturally in certain ripe berries, apples and cherries) although it is prepared commercially from Corn syrup. Pharmaceutical grade Sorbitol is supplied as an odourless, white or almost colourless, crystalline, hygroscopic powder.
Pharmacopoeial Compliance: USP-NF; Ph.Eur; B.P; J.P; I.P
Synonyms and Trade Names: Sorbitol; D-Sorbitol; 1,2,3,4,5,6-hexanehexol; E420; C*PharrnSorbidex; Liponic 70- NC; Liponic 76-NC; Meritol; Neosorb; Sorbitab; Sorbitol Instant; Sorbogem
Uses and Applications: Humectant; Plasticizer; Stabilizing Agent; Sweetening Agent; Tablet and Capsule Diluent
Description
Sorbitol (IUPAC name: O-Glucitol) is a hexahydric alcohol (polyol) that is closely related to Mannose and is isomeric with Mannitol. It is a naturally occurring polyol that can be found in several fruits, including apples, berries, cherries and plums. Owing to its favourable functional properties, including sweetness, humectancy and texturizing effects, Sorbitol is widely utilised in the food industry. In the pharmaceutical industry, Sorbitol is used both as an excipient and an intermediate in API synthesis.
Sorbitol was discovered in 1872 by Jean-Baptist Boussingault, a French chemist who is also credited with giving it its current name. It is commercially produced by chemical catalytic hydrogenation of Glucose or Glucose–Fructose mixtures. This approach, however, yields mixtures of Sorbitol and Mannitol that are costly to separate, and thus the production costs for Sorbitol are high relative to other polyols.
Sorbitol occurs as an odourless, white or almost colourless, crystalline, hygroscopic powder. Four crystalline polymorphs and one amorphous form of sorbitol have been identified that have slightly different physical properties, e.g. inciting point. Commercial grades may be in the form of granules, flakes, or pellets some of which are designed to cake less compared with powdered grades or exhibit desirable compression properties. It exhibits a pleasant, cooling, sweet taste and has approximately 50 – 60% of the sweetness of sucrose.
Sorbitol is also available in liquid form and is supplied as a clear, colourless, syrupy liquid which is miscible with water. This grade of Sorbitol is an aqueous solution of a hydrogenated, partly hydrolysed Starch. Partially dehydrated sorbitol solutions are also available, which are produced by partial dehydration of liquid sorbitol.
The USP-NF and J.P lists Sorbitol solution. The Ph.Eur includes partially dehydrated Liquid Sorbitol, Liquid Sorbitol (crystallizing) and Liquid Sorbitol (non-crystallizing).
Chemical Structure & Identifiers
| Chemical Name | D-Glucitol |
| CAS Registration Number | [50-70-4] |
| Empirical Formula | C6H14O6 |
| Molecular weight | 182.17 |
| EC Number | 200-061-5 |
| UNII Code (FDA) | 506T60A25R |
Regulatory Status
Sorbitol is an approved pharmaceutical excipient, cosmetic ingredient and food additive. It is listed in all the major pharmacopoeia and widely used in several oral, topical and injectable pharmaceutical products. Sorbitol is considered GRAS in the United States and is approved in the EU and many other countries worldwide and is currently the most widely used polyol (with the highest market share of all polyols globally).
Physicochemical Properties
| Physical state | Solid, powder |
| Appearance | White or almost colorless, crystalline powder |
| pH | pH = 4.5—7.0 (10% w/v aqueous solution) |
| Compressibility | Compression characteristics and the degree of lubrication required vary, depending upon the particle size and grade of sorbitol used. Spray-dried grades exhibit better compression characteristics than standard grades |
| Bulk density | 0.4 – 0.7 g/ml |
| Tapped density | 0.4 – .07 g/ml |
| True density | 1.507 g/ml |
| Flowability | Flow characteristics vary depending upon the particle size and grade of sorbitol used. Fine powder grades tend to be poorly flowing, while granular grades have good flow properties |
| Heat of solution – | 110.9 J/g |
| Melting point | Anhydrous form: 110 – 112 OC; Gamma polymorph: 97.7 OC; Metastable form: 93 oC |
| Moisture content | Sorbitol is a very hygroscopic powder. Handling and processing of Sorbitol at relative humidities >60% (at 25 oC) should be avoided |
| Osmolality | A 5.48% w/v aqueous solution of sorbitol hemihydrate is iso-osmotic with serum |
| Particle size distribution | Particle size distribution varies by the grade of Sorbitol. For fine powder grades, typically 87% <125µm in size; for granular grades, 22% <125µm, 45% between 125 and 250µm, and 33% between 250 and 590µm. Individual suppliers’ literature should be consulted for further information. |
| Solubility | Freely soluble in water and in ethanol (95%) |
Pharmacopeoeal Specifications
| USP-NF | Ph.Eur | JP | |
| Official name | Sorbitol | Sorbitol | D-Sorbitol |
| Definition | specified | specified | specified |
| Authorised uses | Excipient | Excipient | Excipient |
| Identification | specified | specified | specified |
| Characters | n/a | specified | n/a |
| Acidity or alkalinity | n/a | n/a | specified |
| pH | 3.5 -7.0 | n/a | n/a |
| Appearance of solution | specified | specified | specified |
| Arsenic | n/a | n/a | ≤ 1.3 ppm |
| Chloride | ≤ 0.005% | n/a | ≤ 0.005% |
| Sulfade | ≤ 0.01% | n/a | ≤ 0.006% |
| Conductivity | n/a | ≤ 20µ Scm-1 | n/a |
| Glucose | n/a | n/a | specified |
| Heavy metals | n/a | n/a | ≤ 5 ppm |
| Lead | n/a | ≤ 0.5 ppm | n/a |
| Microbial contamination | n/a | specified | n/a |
| Bacterial | ≤ 103 cfu/g | ≤ 102 cfu/g | n/a |
| Fungi | ≤ 102 cfu/g | ≤ 102 cfu/g | n/a |
| Bacterial endotoxins | specified | specified | n/a |
| Nickel | ≤ 1µg/g | ≤ 1 ppm | specified |
| Reducing sugars | ≤ 0.3% | ≤ 0.2% | n/a |
| Related products | n/a | ≤ 0.1% | n/a |
| Residue on ignition | ≤ 0.1% | n/a | ≤ 0.02% |
| Total sugars | n/a | n/a | specified |
| Water | ≤ 1.5% | ≤ 1.5% | ≤ 2.0% |
| Assay (anhydrous basis) | 91.0 -100.5% | 97.0 -102.0% | ≥ 97.0% |
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
Sorbitol is a popular polyol that has been used as an excipient in formulations of various drug products. It is a multifunction raw material that may be used as a humectant, plasticizer, stabilizing agent, sweetening agent, and tablet and capsule diluent. It is also used extensively in cosmetics and food products.
Bulking agent in tablets and capsules
Sorbitol is used as a diluent in tablet formulations prepared either via wet granulation or direct compression. Spray-dried grades of Sorbitol possess the required functional properties to serve as fillers and dry binders due to their excellent compressibility, as well as the fact that they are non-cariogenic, non-acidogenic and sugar-free. These properties make Sorbitol a suitable material for use in different types of powder blends, premixes, granules, pellets, swallowable tablets, chewable tablets, effervescent tablets and medicated confectionery. It is particularly useful in chewable tablets owing to its pleasant, sweet taste and cooling sensation in the mouth.
Bulk Sweetener in oral liquids
Sorbitol has approximately 60% the sweetness of Sucrose. It also works well with other ingredients and may even be synergistic with other sweeteners. Thus, when used in combination a synergistic blend is obtained which provides taste, economic and stability advantages compared with individual sweeteners. In liquid preparations, Sorbitol is used as a vehicle in sugar-free formulations and as a stabilizer for drug, vitamin, and antacid suspensions. It may be substituted for Sucrose to prepare 70 – 90% w/v syrups.
Plasticizer and humectant
In capsule formulations, Sorbitol is used as a plasticizer for gelatin capsules. Sorbitol has been used as a plasticizer in film formulations. In cosmetic formulations, the humectant properties are utilised to improve the moisturising properties of formulations.
Other uses
Sorbitol is used in liquid parenteral biologic formulations to stabilise biological molecules in the liquid state.
It has been used as a carrier to enhance the dissolution rate of drug substances such as Indomethacin.
In liquids (syrups) Sorbitol is effective in preventing crystallization around the cap of bottles.
Sorbitol is additionally used in injectable and topical preparations, and therapeutically as an osmotic laxative.
Key advantages of Sorbitol
- Provides bulk and sweetness with a clean, cool pleasant taste
- Lower calories than Sucrose at 2.6 calories/g (compared to 4 calories/g)
- An excellent humectant, texturizing and anti-crystallizing agent for a range of applications
- Highly versatile excipient that is used in a wide variety of products, including swallow and chewable tablets, sugar-free candies, chewing gums, as well as in sugar-free food products
- Non-cariogenic
- A useful alternative for individuals with diabetes
Safety and Precautions
Sorbitol occurs naturally in several edible fruits and berries. When consumed in food and pharmaceutical products, Sorbitol is considered a safe substance. Safety has been supported by many studies reported in the scientific literature. The Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) has concluded that Sorbitol is safe. An acceptable daily intake (ADI) for sorbitol of “not specified,” meaning no limits are placed on its use.
Following oral ingestion, Sorbitol is absorbed more slowly from the gastrointestinal tract than Sucrose. It is subsequently metabolized in the liver to Fructose and Glucose. It has a caloric value is approximately 16.7 J/g and is better tolerated by diabetic patients than Sucrose. For this reason, Sorbitol is often added to sugar-free liquid products. However, it is not regarded as unconditionally safe for individuals with diabetes.
Incidences of adverse reactions to Sorbitol are mainly due to its laxative effects following oral intake. Ingestion of large quantities of Sorbitol (>20 g/day in adults) may therefore be harmful and is best avoided. Since Sorbitol is not easily fermented by oral microflora, it has only a limited impact on dental plaque pH, thus it is generally considered to be non-cariogenic. However, Sorbitol is generally considered to be more irritating than mannitol.
Toxicology: LD50 (mouse, IV): LD50 (rat, IV): 7.1 g/kg; LD50 (rat, SC): 29.6 g/kg
Stability and Storage Conditions
Sorbitol is a very stable and chemically unreactive substance. It can withstand high temperatures and does not participate in Maillard (browning) reactions. Sorbitol is also compatible with most excipients. It exhibits excellent stability in the air in the absence of catalysts as well as in cold dilute acids and alkalis. Sorbitol does not darken or decompose at elevated temperatures or in the presence of amines.
In the bulk state, however, Sorbitol is hygroscopic. It is assigned a shelf life of 24-36 months. Sorbitol should be stored in an airtight container in a cool, dry place.
When handling bulk material adequate PPE is recommended since it may be irritant to the eyes. Eye protection, gloves and a dust mask or respirator are recommended.
Sustainability and Environmental Impact
A sustainability assessment has not been undertaken for Sorbitol. However, Sorbitol is believed to be derived from non-critical raw materials. It also imparts minimal long-term impact on ecology and marine ecosystems.
Manufacturers & Suppliers
- Merisorb® Sorbitol
- Meritol® Sorbitol
- Neosorb® Sorbitol
- C*PharrnSorbidex® Sorbitol
Additional Resources (Downloads)
References and Literature Used
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