Isosorbides

Fig. 4. AnhydriZation of sorbitol (1) to 1,4-sorbitan (2), 3,6-sorbitan (3), 2,5-ahydro-L-iditol (4), and isosorbide (5). Also shown are isomannide (6) and...

Loss of a second molecule of water occurs on heating (1) (106,107), (2), or (3) (108) with concentrated sulfuric or hydrochloric acid forming 1,4 3,6-dianhydro-D-glucitol (isosorbide) (5). Mannitol and iditol anhydrize under similar conditions to isomannide (6) and isoidide (7), respectively. In (6), both hydroxyl groups are oriented toward each other (endo) ia (7), both are oriented away from each other (exo) and ia isosorbide (5), one hydroxyl is endo and the other exo. XyUtol loses two moles of water to form l,3 2,5-dianhydrox5litol (109). 

Reaction of olefin oxides (epoxides) to produce poly(oxyalkylene) ether derivatives is the etherification of polyols of greatest commercial importance. Epoxides used include ethylene oxide, propylene oxide, and epichl orohydrin. The products of oxyalkylation have the same number of hydroxyl groups per mole as the starting polyol. Examples include the poly(oxypropylene) ethers of sorbitol (130) and lactitol (131), usually formed in the presence of an alkaline catalyst such as potassium hydroxide. Reaction of epichl orohydrin and isosorbide leads to the bisglycidyl ether (132). A polysubstituted carboxyethyl ether of mannitol has been obtained by the interaction of mannitol with acrylonitrile followed by hydrolysis of the intermediate cyanoethyl ether (133). 

Isomerization of sorbitol, D-mannitol, L-iditol, and dulcitol occurs in aqueous solution in the presence of hydrogen under pressure and a nickel—kieselguhr catalyst at 130—190°C (160). In the case of the first three, a quasiequiUbrium composition is obtained regardless of starting material. Equilibrium concentrations are 41.4% sorbitol, 31.5% D-mannitol, 26.5% L-iditol, and 0.6% dulcitol. In the presence of the same catalyst, the isohexides estabUsh an equihbrium at 220—240°C and 15.2 MPa (150 atm) of hydrogen pressure, having the composition 57% isoidide, 36% isosorbide, and 7% isomannide (161). 

Manufacture of vitamin C starts with the conversion of sorbitol to L-sorbose. Sorbitol and xyHtol have been used for parenteral nutrition following severe injury, bums, or surgery (246). An iron—sorbitol—citric acid complex is an intramuscular bematinic (247). Mannitol administered intravenously (248) and isosorbide administered orally (249) are osmotic diuretics. Mannitol hexanitrate and isosorbide dinitrate are antianginal dmgs (see Cardiovascular agents). 

Anhydrosorbitol Esters. Eatty acid esters of anhydrosorbitol (see Alcohols,polyhydric) are the second largest class of carboxyHc ester surfactants. The important commercial products are the mono-, di-, and triesters of sorbitan and fatty acids (Table 18). Sorbitan is a mixture of anhydrosorbitols, principally 1,4-sorbitan (1) and isosorbide (2) ... 

A series of sorbitol-based nonionic surfactants are used ia foods as water-ia-oil emulsifiers and defoamers. They are produced by reaction of fatty acids with sorbitol. During reaction, cycHc dehydration as well as esterification (primary hydroxyl group) occurs so that the hydrophilic portion is not only sorbitol but also its mono- and dianhydride. The product known as sorbitan monostearate [1338-41 -6] for example, is a mixture of partial stearic and palmitic acid esters (sorbitan monopalmitate [26266-57-9]) of sorbitol, 1,5-anhydro-D-glucitol [154-58-8] 1,4-sorbitan [27299-12-3] and isosorbide [652-67-5]. Sorbitan esters, such as the foregoing and also sorbitan monolaurate [1338-39-2] and sorbitan monooleate [1338-43-8], can be further modified by reaction with ethylene oxide to produce ethoxylated sorbitan esters, also nonionic detergents FDA approved for food use. 

Isosorbide is rapidly absorbed and undergoes rapid first-pass metaboHsm by the Hver. The bioavaUabUity of the subHngual and chewable tablets is 59% and 22%, respectively, for the regular tablet. Isosorbide is metabolized to isosorbide-2-mononitrate and isosorbide-5-mononitrate, both of which have pharmacologic activity. The elimination half-Hves of subHngual and po isosorbide dinitrate ate 1 and 4 h, respectively. Those of the 2- and 5-mononitrate metaboHtes are 1.5—3.1 h and 4—5.6 h, respectively. The two metaboHtes prolong the elimination half-life of the dinitrate. Adverse effects with isosorbide are similar to those described for nitroglycerin (99). 

Passive transdermal dehvery systems on the market tend to be either matrix or membrane controUed. In matrix devices, the stmctural and molecular characteristics of the dmg-polymer matrix determine dmg release. Examples of polymer matrix-controUed diffusional systems for angina prophylaxis include Nitro-Dur and Nitrodisc, which provide transdermal dehvery of nitroglycerin [55-63-0], and Erandol, a tape that releases isosorbide dinitrate [87-33-2]. Matrix diffusional systems have been used for dehvering dmgs with a wide therapeutic index. 

ISOSORBIDE DINITRATE MIXTURE with not less than 60X lactose, 2907 87-33-2... 

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