Sugar Alcohol Used in Pharmaceutical Formulations: Sorbitol

Sorbitol is a sugar alcohol that is an isomer of mannitol, also known as D-Glucitol. It is a carbohydrate alcohol found in many fruits in nature (apples, prunes, cherries and grapes). Sorbitol, first isolated in 1872 from the rowan fruit, noted in Latin as Sorbus aucuparia, is produced commercially from glucose (dextrose). It is a polyol (sugar alcohol) obtained through catalytic hydrogenation of dextrose (glucose). It is odourless and available in white or colourless form, with a crystalline structure and high moisture-absorbing properties. Four crystalline polymorphs and one amorphous form have been identified, each with different physical properties. Sorbitol products, available in powder, flake and granule forms, each with different properties, serve different purposes in the pharmaceutical industry. While sorbitol has a sweetening capacity of 50–60% that of sucrose in terms of taste intensity, it is a step ahead of other sugar alcohols in terms of cooling sensation. (Wikipedia citation)

1.2. Applications:

1. Used in many baked goods and confectionery. It is a low-calorie sweetener and bulking agent. 2. Used in the food industry as a sweetener and humectant. 3. Included in formulations for toothpaste, gum, cough lozenges, cosmetics and tobacco products. 4. Sorbitol, which is not affected by insulin and does not increase blood sugar index, is widely used in formulations of products manufactured for diabetics. 5. While it does not cause plaque formation on teeth, it is a good additive for chewing gums and serves as a humectant and sweetener in these products. 6. Used also as a flavouring agent, sorbitol does not decompose and finds application as raw material in vitamin C manufacture in the pharmaceutical industry. 7. Used as a sweetener in most diet food products, such as diet beverages, ice cream, peppermint candy, cough syrup, sugar-free gum.  

1.2.1. Pharmaceutical Industry Applications:

Humectant, plasticiser; sweetener; tablet and capsule filler. Sorbitol is mostly used as an excipient in the pharmaceutical industry. Pharmaceutical manufacturing currently uses sorbitol as a filler in tablet formulations derived from solid dosage forms using both wet granulation and direct compression methods. It is used in chewing tablets with consideration for its sweetening property and cooling sensation, and in gelatin capsules due to its plasticising property. Due to its sweetening property, it is used in products that must not contain sugar, in vitamins, in antacid suspension products, and in syrup formulations primarily to prevent crystallisation, and specifically to prevent crystallisation of product that accumulates between the cap and bottle.   (Tereos-Syral citation) Globally, it appears as the most widely used polyol derivative with annual production of 800,000 tonnes. For other polyols, xylitol is reported at 200,000 tonnes, mannitol at 180,000 tonnes, and maltitol at 160,000 tonnes.

1.2.1.1. Sorbitol as an Excipient

When compared with lactose derivatives frequently used in the pharmaceutical industry, sorbitol and the polyols present in it have significant advantages. Since a large portion of active ingredients used in the pharmaceutical industry are developed using biotechnological processes, they can interact with reducing sugars such as lactose and cause reactions with the amino groups of active ingredients. Polyols do not contain reducing sugars, so they prevent reaction formation against such reactive active ingredients. Besides polyols being stable against reaction formation, they offer a broad product range with functional properties produced through spray drying or granulation techniques with different particle sizes for tablet formulations.

1.2.1.2. Sorbitol in Solid Dosage Forms

There are different types of tablet forms in which sorbitol is used in the industry. The most important among these are chewing tablets, mouth-dissolving tablets and lozenges. Since the dispersion in the mouth of all the aforementioned forms takes place in a short time measured in seconds, the taste sensation it leaves in the mouth and the acceptability of the drug by the patient are the most critical factors. The taste intensities of polyols used in the pharmaceutical industry are indicated below in order, and the selection can be made depending on the amount of active ingredient in the formulation and the taste of the active ingredient. Cooling ability: Mannitol<Maltitol<Sorbitol<XylitolFlavour compatibility: Peppermint flavours yield more effective results with xylitol and sorbitol, and fruit flavours with maltitol. Compressibility: Maltitol<Xylitol<Mannitol<Sorbitol Disintegration time: Mannitol<Maltitol<Xylitol<Sorbitol In terms of taste sensation left in the mouth, mannitol has a creamy taste, maltitol has a crispy taste, and sorbitol and xylitol have a soft taste.   The spray drying method allows the pressure produced via air hoses to pass through an injector gun, and the product in solution form passing through the injector to reduce particle size and increase surface area through high-temperature application. It is also suitable for application in heat-sensitive products. From a technical perspective, spray drying consists of four main stages. 1. Atomisation: Liquid feed solution is atomised through pressure via injector guns and sent to the environment. 2. Drying: The drying process is carried out when the product in solution form sent to the environment via atomisation pressure comes into contact with heated nitrogen gas or air in the environment. The performance of the drying process varies in relation to droplet size, solution flow rate and drying temperature. 3. Particle Formation: The solution product in droplet form transferred to the environment via atomisation pressure from the injector gun has its water evaporated by the effect of heat in the environment and the product is obtained in solid form. 4. Product Collection: The powdered product is collected from exit air channels and dust filters. The process takes place in a few seconds. Among sorbitol manufacturing techniques, spray drying is the most expensive but, considering the contributions of the product obtained to the pharmaceutical industry, spray-dried sorbitol is the most practical product. (Indian Journal of Science citation) Engin Sarı - Senior Technical Product Manager / Pharmaceutical Division / IMCD Sources / Resources: 1. www.tereos-syral.com 2. British Journal of Nutrition (2001) Suppl 1, S 31–S45. 3. en.wikipedia.org/wiki/Sorbitol 4. Indian Journal of Science and Technology vol 2 No: 10 (Oct 2009). 5. United States Patent Office 3,308,171.