International Numbering System (INS) for Food Additives: 420
Food additives Europe numbers: E420
Functional Category
Humectant; plasticizer; stabilizing agent; sweetening agent; tablet and capsule diluent.
Applications in Pharmaceutical Formulation
Sorbitol is widely used as an excipient in pharmaceutical formulations. It is also used extensively in cosmetics and food products; see Table I. Sorbitol is used as a diluent in tablet formulations prepared by either wet granulation or direct compression.(1–5) It is particularly useful in chewable tablets owing to its pleasant, sweet taste and cooling sensation. In capsule formulations it is used as a plasticizer for gelatin. Sorbitol has been used as a plasticizer in film formulations.(6,7) In liquid preparations(8) sorbitol is used as a vehicle in sugar-free formulations and as a stabilizer for drug,(9) vitamin,(10,11) and antacid suspensions. Furthermore, sorbitol is used as an excipient in liquid parenteral biologic formulations to provide effective protein stabilization in the liquid state.(12) It has also been shown to be a suitable carrier to enhance the in vitro dissolution rate of indometacin.(13) In syrups it is effective in preventing crystallization around the cap of bottles. Sorbitol is additionally used in injectable(14) and topical preparations, and therapeutically as an osmotic laxative. Sorbitol may also be used analytically as a marker for assessing liver blood flow.(15)
Description
Sorbitol is D-glucitol. It is a hexahydric alcohol related to mannose and is isomeric with mannitol. Sorbitol occurs as an odorless, white or almost colorless, crystalline, hygroscopic powder. Four crystalline polymorphs and one amorphous form of sorbitol have been identified that have slightly different physical properties, e.g. melting point.(3) Sorbitol is available in a wide range of grades and polymorphic forms, such as granules, flakes, or pellets that tend to cake less than the powdered form and have more desirable compression characteristics. Sorbitol has a pleasant, cooling, sweet taste and has approximately 50–60% of the sweetness of sucrose. See also Section 18.
Stability and Storage Conditions
Sorbitol is chemically relatively inert and is compatible with most excipients. It is stable in air in the absence of catalysts and in cold, dilute acids and alkalis. Sorbitol does not darken or decompose at elevated temperatures or in the presence of amines. It is nonflammable, noncorrosive, and nonvolatile. Although sorbitol is resistant to fermentation by many microorganisms, a preservative should be added to sorbitol solutions. Solutions may be stored in glass, plastic, aluminum, and stainless steel containers. Solutions for injection may be sterilized by autoclaving. The bulk material is hygroscopic and should be stored in an airtight container in a cool, dry place.
Incompatibilities
Sorbitol will form water-soluble chelates with many divalent and trivalent metal ions in strongly acidic and alkaline conditions. Addition of liquid polyethylene glycols to sorbitol solution, with vigorous agitation, produces a waxy, water-soluble gel with a melting point of 35–408C. Sorbitol solutions also react with iron oxide to become discolored. Sorbitol increases the degradation rate of penicillins in neutral and aqueous solutions.(16)
Safety
Sorbitol is widely used in a number of pharmaceutical products and occurs naturally in many edible fruits and berries. It is absorbed more slowly from the gastrointestinal tract than sucrose and is metabolized in the liver to fructose and glucose. Its caloric value is approximately 16.7 J/g (4 cal/g). Sorbitol is better tolerated by Table II: Pharmacopeial specifications for sorbitol. Test JP XV PhEur 6.4 USP32–NF27 Identification þþþ Characters — þ — Acidity or alkalinity þ — — pH — — 3.5–7.0 Appearance of solution þþþ Arsenic 41.3 ppm — — Chloride 40.005% — 40.005% Sulfate 40.006% — 40.01% Conductivity — 420 mS cm1 — Glucose þ — — Heavy metals 45 ppm — — Lead — 40.5 ppm — Microbial contamination — þ — Bacterial — 4102 cfu/g 4103 cfu/g Fungi — 4102 cfu/g 4102 cfu/g Bacterial endotoxins — þ þ(a) Nickel þ 41 ppm 41 mg/g Reducing sugars — 40.2% 40.3% Related products — 40.1% — Residue on ignition 40.02% — 40.1% Total sugars þ — — Water 42.0% 41.5% 41.5% Assay (anhydrous basis) 597.0% 97.0–102.0% 91.0–100.5% (a) 44 USP Endotoxin Units per g for parenteral dosage forms having a concentration of less than 100 g of sorbitol per L and 42.5 USP Endotoxin Units per g for parenteral dosage forms having a concentration of 100 g or more of sorbitol per L. S 680 Sorbitol diabetics than sucrose and is widely used in many sugar-free liquid vehicles. However, it is not considered to be unconditionally safe for diabetics. Reports of adverse reactions to sorbitol are largely due to its action as an osmotic laxative when ingested orally,(17–19) which may be exploited therapeutically. Ingestion of large quantities of sorbitol (>20 g/day in adults) should therefore be avoided. Sorbitol is not readily fermented by oral microorganisms and has little effect on dental plaque pH; hence, it is generally considered to be noncariogenic.(20) Sorbitol is generally considered to be more irritating than mannitol. LD50 (mouse, IV): 9.48 g/kg(21) LD50 (mouse, oral): 17.8 g/kg LD50 (rat, IV): 7.1 g/kg LD50 (rat, SC): 29.6 g/kg