Amorphous form hygroscopicity

Another physical property that can affect the appearance, bioavailability, and chemical stability of pharmaceuticals is degree of crystallinity. Amorphous materials tend to be more hygroscopic than their crystalline counterparts. Also, there is a substantial body of evidence that indicates that the amorphous forms of drugs are less stable than their crystalline counterparts [62]. It has been reported, for example,... 

Lactose may be obtained in two crystalline forms a-lactose and P-lactose (in addition to amorphous forms). The alpha form is obtained when water is incorporated into the lattice structure during crystallization (usually by supersaturation below 93.5°C) (5). Alternatively, the beta form does not contain water and exists as a non-hygroscopic and anhydrous form. Amorphous lactose is formed when either the crystallization is rapid or sufficient transient energy is introduced into the crystalline forms (74), i.e., spray drying (75), micronization and milling (76), freeze-drying, and anti-solvent crystallization (77). 

The yellow, amorphous variety is unstable and its identity is a little doubtful. It is stated to be obtained sometimes from the red, amorphous form by evaporation of a solution of the latter in hydrochloric acid, and it may also result from the ignition of ammonium meta-vanadate or from the decomposition of vanadates by acids. According to Bleecker it is most conveniently prepared by the electrolytic decomposition of copper vanadate.5 It becomes brick red on being heated, and is similar to the red variety in its general properties, except that it appears to be less hygroscopic and less soluble its saturated aqueous solution contains between 300 and 400 mgm. per litre.6... 

Some excipients contain a certain amount of amorphous form such as spray-dried lactose,27 and others are hygroscopic, such as microcrystalline cellulose.28 These excipients will adsorb water, which causes a change in the micro-environment of the formulation. If the drug substance is moisture-sensitive, degradation may occur quickly. Therefore, consider both drug-excipient compatibility and excipient impurity profile in selecting excipients for low-dose drug products. 

Alkyl ether sulphates are used relatively little in laundry products, especially in solid ones. The surfactant has a very poor solid form, the pure product being amorphous, somewhat hygroscopic and sticky. Commercial dry ether sulphates are unknown other than as blends of 50% with carrier solids, such as sodium carbonate. In liquid formulations, 3-mol ether sulphates can be used to give improved solubility and hard water tolerance in unbuilt liquids and amine salts are occasionally used. 

Sorbitol occurs as an odorless, white or almost colorless, crystalline, hygroscopic powder. Eour crystalline polymorphs and one amorphous form of sorbitol have been identified that have slightly different physical properties, e.g., melting point. Sorbitol is available in a wide range of grades and polymorphic forms such as granules, flakes, or peUets that tend to cake less than the powdered form and have more desirable compression characteristics. Sorbitol has a pleasant, coohng, sweet taste and has approximately 50-60% of the sweetness of sucrose. 

This conclusion agrees with early observations that crystalline forms of penicillin were much more stable than amorphous forms l c, 20. Florey, et al. reported in 1949 that the alkali salts of the penicillins are hygroscopic in the impure state, but not when crystalline... 

All three constituents In the form of hydrochlorides arc white, amorphous, slightly hygroscopic powders, melting with decompn at indefinite temperatures. 

Cefazolin sodium is capable of existing in a number of crystalline modifications, but the amorphous state is produced by the lyophilization process [38]. The amorphous form retained its nature at relative humidities less than 56% but converted completely to the pentahydrate above 75% RH. Interestingly, the hygroscopicity of the amorphous form was essentially similar to that exhibited by the dehydrated monohydrate or dehydrated a-form. Lamotrigine mesylate was also found to exhibit a moisture-dependent amorphous-to-crystalline transition [39]. The transition was found to be independent of the presence of mannitol, whether the amorphous solid was produced by lyophilization or by spray-drying. 

Properties and Structure. Phosphoms(V) oxide, the extremely hygroscopic acid anhydride of the phosphoric acids, exists in several forms but is often referred to by its empirical formula, P2O3. Three crystalline polymorphs, two distinct Hquids, and several amorphous or glassy soHds are recogni2ed. Some properties of the various forms of phosphoric oxide are Hsted in Table 10. 

Dihydrostreptomycin sesquisulfate [5490-27-7] M 461.4, m 250 (dec), 255-265 (dec), [a]p -92.4 (c 1, H2O), pKgsJd)-- 9.5 (NMe), pKes,(2,3) 13.4 (guanidino). It crystallises from H2O with MeOH, -BuOH or methyl ethyl ketone. The crystals are not hygroscopic like the amorphous powder, however both forms are soluble in H2O but the amorphous solid is about 10 times more soluble than the crystals. The free base also crystallises from H20-Me2C0 and has [a]p -92° (aqueous solution pH 7.0). [Solomons and Regina Science 109 515 7949 Wolf et al. Science 109 515 7949 McGilveray and Rinehart J Am Chem Soc 87 4003 1956]. 

Polymetatelluric acid (H2TeO4). ]0 is a white, amorphous hygroscopic powder formed by incomplete dehydration of HgTeOg in air at 160°. Alternatively, in aqueous solution... 

Indinavir sulfate is hygroscopic, and will convert to either an amorphous state or a hydrated form [7]. 

Lactose glass. When a lactose solution is dried rapidly, viscosity increases so quickly that crystallization is impossible. A noncrystalline form is produced containing a- and /J-forms in the ratio at which they exist in solution. Lactose in spray-dried milk exists as a concentrated syrup or amorphous glass which is stable if protected from air, but is very hygroscopic and absorbs water rapidly from the atmosphere, becoming sticky. 

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