Anhydrous crystalline form

Ammonium bisulfite can be used in place of the sulfur dioxide. The solution is treated with activated carbon and filtered to remove traces of sulfur. Excess ammonia is added and the solution evaporated if the anhydrous crystalline form is desired. The crystals ate dried at low temperature in the presence of ammonia to prevent decomposition (61—63). 

Pyridine hydrochloride is extremely hygroscopic the material used must be the anhydrous crystalline form. 

In 1951, Whistler and Durso reported68 the isolation of epimelibiose by partial, acid hydrolysis of the polysaccharide guaran, followed by charcoal-column fractionation of the products. ThA material was obtained in anhydrous crystalline form from a mixture of methyl and butyl alcohols it had m.p. 201°, [a]26D + 120.9° — +124.6° in 36 hr. (c 2, in water). The yield was 2.2% of the weight of guaran used. Epimelibiose has also been produced72" in crystalline form following the ammonia-catalyzed alkaline isomerization of melibiose. 

Tetracaine hydrochloride was also revisited using thermal methods, revealing a complicated system containing six anhydrous crystalline forms, an amorphous form, a hemihydrate, a monohydrate and a tetrahydrate. As with the purine derivative noted above, the identification and classification of these modifications was considerably aided by the use of temperature resolved X-ray diffraction (Giron et al. 1997). 

Terazosin hydrochloride is a drug developed by Abbott Laboratories for the treatment of hypertension and benign prostatic hyperplasia, and marketed as the dihydrate under the trade name Hytrin since 1987. The patent of interest here is U.S. Patent No. 5,504,207 (the 207 patent), tiled in October, 1994 for which the fourth claim is a particular anhydrous crystalline form of terazosin hydrochloride, designated by Abbott as Form IV , a form not marketed by Abbott. In the 207 patent. Form IV is defined by reference to the X-ray powder diffraction pattern, listing the peak positions of several of the peaks. To be within the scope of claim 4 of the 207 patent, a product must be anhydrous terazosin hydrochloride and must exhibit a powder X-ray diffraction pattern having each of the principal peaks identified in claim 4. 

Melting point 130°C (for anhydrous crystalline form) 36.5°C (for pentahydrate). 

Amoxicillin sodium salt is normally prepared in an amorphous form. An anhydrous crystalline form can be obtained [17] by removal of solvent from various solvates, either in the solid state or by displacement in solution with a solvent of lower dielectric constant. 

Hydrates can be polymorphic amiloride hydrochloride, for example, is available in two polymorphic dihydrate forms, each of which can be dehydrated to an anhydrous crystalline form. By milling or compressing both forms, it was shown that Form A was more stable than Form B. Moreover, it was shown that the anhydrate rapidly rehydrated to Form A dihydrate on exposure to atmospheric relative humidity (Jozwiakowski et al. 1993). 

The differences between polymorphs and hydrates are significant. The basis for all these differences is that polymorphs are different crystal structures of the same molecules(s) while hydrates are crystals of the drug molecule with different numbers of water molecules. As discussed above, the hydration state (and therefore the structure) of a crystalline hydrate is a function of the water vapor pressure (water activity) above the solid. Polymorphs, however, are typically only affected by changes in water vapor pressure if water sorption allows molecular motion, which in turn allows a reorganization into a different polymorph (i.e., a solution mediated transformation). This distinction is particularly important in defining the relative free energy of hydrates. A simple (only one molecule) anhydrous crystalline form is a one component system, and the free energy is, practically, specified by temperature and pressure. A crystalline hydrate is a two-component system and is specified... 

Dehydrated hydrates may in principle belong to any of the classes just discussed, but the cases with which the author is familiar (findings not yet published) have all been either channel hydrates or clathrate type structures where water is the guest instead of the host in a cavity and in a nonstoichiometric amount. This subclass deals with crystals that dehydrate even at relatively high partial pressures of water. Therefore, the hydrate that forms in solution dehydrates almost immediately on removal from the mother liquor. When dehydration leaves an intact anhydrous structure that is very similar to the hydrated structure but with lower density, it is classified as a dehydrated hydrate. If there already exists an anhydrous crystalline form of the molecule, the dehydrated hydrate is classified as a polymorph. 

Pyrophosphoric acid (diphosphoric acid), H4P2O7 (P2O5 2H2O), the second member of the linear polyphosphoric acid series, exists in two anhydrous crystalline forms, with melting points of 54.3 and 71.5°C, respectively. Pure pyrophosphoric acid solutions are best prepared by ion exchange from the sodium salt, or by the action of hydrogen sulphide on the insoluble lead salt ... 

Phosphoric acid does not react with anhydrous crystalline forms of Si02, AI2O3, Cr203, Z1O2 and Ti02 at room temperature. Some reaction occurs with the hydrated or colloidal forms of these oxides or with the anhydrous forms themselves if the temperature rises above about 200°C. Below this temperature silica glass is not appreciably attacked by the acid in moderate concentration. 

There arc also some unusual anhydrous crystalline forms, as follows (64)., ... 

The following anhydrous crystalline forms, obtained from the melt, have a SiO MjO ratio of 1 or higher ... 

Dehydration of organic acids leads to corresponding anhydrides, but as stated by Repta and Higuchi [480, 481], the mentioned in the literature dehydrated citric acid is actually anhydrous crystalline form of citric acid or aconitic acid, but not a true anhydride of citric acid. They were able to synthesize and isolate the mono-molecular unsymmetrical anhydride of citric acid. The conversion of citric acid to its anhydride is performed by interacting of the solid acid with an excess of acetic anhydride in glacial acetic acid at 36-38 °C. The melting point of prepared white crystalline solid anhydride is at 121-123 °C. The identification of thise compound was performed by elementary analysis, potentiometric titration, cryoscopic and NMR measurements. From three possible anhydride stractures (A) - symmetrical anhydride, (B) - unsymmetrical anltydride and (C) - intermolecular anhydride. 

The anhydrous crystalline forms of Naproxen [(S)-(-l-)-2-(6-metho3gr-2-naphthyl)propionic acid], (NAPROA) and its sodium salt (NAPRO-S), widely used anti-inflammatory drugs, have been investigated by means of ID and 2D MAS NMR and DFT based calculations. From calculations, ID CP MAS and CRAMPS and 2D H- c MAS-J-HMQC, refocused INEPT, FSLG-HETCOR, and DQ-CRAMPS solid-state NMR experi-... 

Three crystalline modifications of fluocinolone acetonide (Forms A, B and C) were characterised by FTIR, DSC, TG - FTIR, micro-FTIR and XRD [21]. On heating Form A and Form C were converted into Form B. Polymorph A was enantiotropically related to Form B while Form C was monotropically related to B[21]. Giron et al [22] examined tetracaine hydrochloride. Ten different forms were identified six anhydrous crystalline forms, an amorphous form, a hemihydrate, a monohydrate and a tetrahydrate. The anhydrous Form I is the stable thermodynamic modification at ambient temperature. Form 2 was reversibly enantiotropic to Form I. The other four modifications (3, 4, 5 and 6) were monotropic polymorphs of Form I. Only Form 1 and Form 5 were stable at room temperature [22]. 

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