Sorbitol crystallization

Starch-PVA films plasticized with glycerol embrittled with age. A study of various polyols was undertaken to identity plasticizers which would reduce this tendency.131 It was demonstrated that sorbitol and glycol glycoside performed well. When sorbitol alone was used, it migrated to the surface and crystallized. When sorbitol and glycerol were used in a 3 1 w/w ratio, the films were stable and showed no evidence of sorbitol crystallization. Substituting plasticizer with PVA did not adversely affect the films when starch was substituted for plasticizer, the films became more susceptible to aging. 

Keywords refractive index, optical clarity, haze, transparency, nucleation, opacity, clarifers, sorbitol, crystallization. 

Selection of the most suitable chemical form of the active principle for a tablet, while not strictly within our terms of reference here, must be considered. For example, some chloramphenicol esters produce little clinical response [13], There is also a significant difference in the bioavailability of anhydrous and hydrated forms of ampicillin [14], Furthermore, different polymorphic forms, and even crystal habits, may have a pronounced influence on the bioavailability of some drugs due to the different dissolution rates they exhibit. Such changes can also give rise to manufacturing problems. Polymorphism is, of course, not restricted to active ingredients, as shown, for example, in an evaluation of the tableting characteristics of five forms or sorbitol [15]. 

Zentner and coworkers [24,26] utilized this information in their development of a system that releases this drug over a 24 hr period. The use of NaCl to modulate the release of diltiazem presents an interesting problem in that the concentration of the solubility modifier must be maintained within certain limits and below its saturation solubility within the device. To solve this problem, core formulations were developed that contained both free and encapsulated NaCl. The encapsulated NaCl was prepared by placing a microporous coating of cellulose acetate butyrate containing 20 wt% sorbitol onto sieved NaCl crystals. The coated granules released NaCl over 12-14 hr period via an osmotic mechanism into either water or the core tablet formulation. The in vitro release profile for tablets (core I devices) containing 360 mg of diltiazem HC1 and 100 mg of NaCl equally divided between the immediate release and controlled release fractions... 

There appears to be no physical (e.g., crystal habit or morphology) or chemical (e.g., surface groups) correlation to identify which nucleating agent works best with which polymer matrix. However, it is known that dibenzylidene sorbitol works best with PP (it is sometimes called a clarifier because it enhances transparency), and inorganic benzoate salts are successful with PET. 

L-Iditol (sorbi6rite), the last of the four naturally occurring hexitols, occurs in service berries along with sorbitol. After removing sorbitol from the juice by fermentation to L-sorbose with the sorbose bacterium, Acetobacter xylinum, the n-iditol is crystallized as a benzylidene derivative. It has been prepared by the action of sodium amalgam on... 

The separation of mixtures of hexitols has long been a difficult problem. The removal of sorbitol from L-iditol by bacterial action is a classical example. Destruction of one component as a means of separation is drastic and is applicable to only a few mixtures. Even from an analytical point of view, separation has been difficult. The proportions of D-mannitol and sorbitol in the reduction products of D-fructose may be determined approximately by crystallizing and weighing the D-mannitol, but the amount of D-mannitol still in solution remains an unknown quantity. 

In pharmaceutical applications, sorbitol is used as a tablet diluent in wet granulation or dry compression formulations. It is commonly used in chewable tablets because of its sweet taste, and it is also used as a plasticizer for gelatin in capsule formulations. Sorbitol is utilized in sugar-free liquid preparations and as a stabilizer for drug, vitamin, and antacid suspensions. When it is used in syrups, crystallization around bottle caps is prevented. 

The sorbitol solution produced from hydrogenation is purified in two steps [4]. The first involves passing the solution through an ion-exchange resin bed to remove gluconate and other ions. In the second step, the solution is treated with activated carbon to remove trace organic impurities. The commercial 70% sorbitol solution is obtained by evaporation of the water under vacuum. The solid is prepared by dehydration until a water-free melt is obtained which is cooled and seeded. The crystals are removed continuously from the surface (melt crystallization). The solid is sold as flakes, granules, pellet, and powder forms in a variety of particle size distributions. 

Sorbitol exhibits a number of different crystal forms and there is little agreement in the literature concerning the number of polymorphs, the existence of hydrated species, melting points of the various forms, and even nomenclature [7-14]. Much of the data in the literature was collected on commercial powders that were not fully described, or whose history is not fully known. Table 2 attempts to summarize the various forms based on reports by DuRoss [7] and Quinquenet et al. [8]. 

It has been reported that the y-form, which melts at approximately 101°C, is the thermodynamically most stable form at room temperature and that the sorbitol system is monotropic [8]. Studies of the various forms show that upon standing or upon stress conditions, sorbitol will convert to the y-form [7]. However, a solution calorimetry study performed on selected crystal forms of sorbitol reports that sorbitol hydrate is the most stable form followed by the y-form [18]. 

The commercial crystal form produced after 1975 is the y-form. XRPD powder patterns collected on the various sorbitol samples listed in Table 1 are in agreement with the reported y-form [15], and are shown in Figure 3. The listing of peak positions, d-spacings, and relative intensities for this crystal form is given in Table IV. 

There is also a risk that sweeteners in solution may crystallize with time and/or temperature changes. However, sorbitol is not readily fermented by oral microorganisms and has little effect on dental plaque pH. It is also often used in syrups to prevent crystallization around the cap of bottles. 

Lactitol. Lactitol (4-0-/ -D-galactopyranosyl-D-sorbitol), is a synthetic sugar alcohol produced on reduction of lactose, usually using Raney nickel. It can be crystallized as a mono- or di-hydrate. Lactitol is not metabolized by higher animals it is relatively sweet and hence has potential as a non-nutritive sweetener. It is claimed that lactitol reduces the absorption of sucrose, blood and liver cholesterol levels and to be anticariogenic. It has applications in low-calorie foods (jams, marmalade, chocolate, baked goods) it is non-hygroscopic and can be used to coat moisture-sensitive foods, e.g. sweets. 

Nitrosorbite (Sorbitol hexanitrate) d-Sorbite occurs in the berries of the mountain ash, but is more readily procured by the electrolytic reduction of d-glucose. It crystallizes with one molecule of water in small crystals which lose their water when heated and melt at about 110°. Nitrosorbite, isomeric with nitromannite, exists as a viscous liquid and has never been obtained in the crystalline state. It is used in non-freezing dynamites. 

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