Polymorphs melting point

Temperature where nematic droplets appear due to cyclotrimerization reaction on POM when heating at 10°C/min. Polymorphic melting point behavior due to mixture of isomers. 

Crystalline Silica. Sihca exists in a variety of polymorphic crystalline forms (23,41—43), in amorphous modifications, and as a Hquid. The Hterature on crystalline modifications is to some degree controversial. According to the conventional view of the polymorphism of siHca, there are three main forms at atmospheric pressure quart2, stable below about 870°C tridymite, stable from about 870—1470°C and cristobaHte, stable from about 1470°C to the melting point at about 1723°C. In all of these forms, the stmctures are based on SiO tetrahedra linked in such a way that every oxygen atom is shared between two siHcon atoms. The stmctures, however, are quite different in detail. In addition, there are other forms of siHca that are not stable at atmospheric pressure, including that of stishovite, in which the coordination number of siHcon is six rather than four. 

Alkenoic acids also have polymorphic crystalline forms. For example, both oleic and elaidic acids are dimorphic with melting points of 13.6 and 16.3°C for oleic, and 43.7 and 44.8°C for elaidic acid (14). 

For (Z)-cinnamic acid [102-94-3], three distinct polymorphic forms have been characteri2ed. The most stable form, referred to as aHocinnamic acid, has a melting point of 68°C, and the two metastable forms, isocinnamic acids, have melting points of 58°C and 42°C, respectively. (E)-Cinnamic acid can be converted to the (Z)-isomer photochemicaHy through kradiation of a solution with ultraviolet light. 

Chemical development Proof of structure and configuration are required as part of the information on chemical development. The methods used at batch release should be validated to guarantee the identity and purity of the substance. It should be established whether a drug produced as a racemate is a true racemate or a conglomerate by investigating physical parameters such as melting point, solubility and crystal properties. The physicochemical properties of the drug substance should be characterized, e.g. crystallinity, polymorphism and rate of dissolution. 

Solid compounds can have four morphic states polymorphic, pseudo-polymorphic (solvates), amorphous, and desolvated solvates. Crystals usually exhibit narrow melting point ranges and defract light under an optical microscope. When a change in the arrangement of... 

A different situation exists if the compound exists as form I and form III. This is referred to as a monotropic system, and here III is unstable relative to I over the whole solid range. In this case, however, the melting point of the unstable polymorph is lower than that of the stable (Tis lower than T ). 

Molecular structure and weight Melting point Thermal profile Particle size and shape Hygroscopicity potential Ionization constant Light stability Optical activity pH solubility profile pH stability profile Polymorphism potential Solvate formation... 

A polymorph is a solid crystalline phase of a compound resulting from the possibility of at least two different crystal lattice arrangements of that compound in the solid state [42], Polymorphs of a compound are, however, identical in the liquid and vapor states. They usually melt at different temperatures but give melts of identical composition. Two polymorphs of a compound may be as different in structure and properties as crystals of two different compounds [43,44], Apparent solubility, melting point, density, hardness, crystal shape, optical and electrical properties, vapor pressure, etc. may all vary with the polymorphic form. The polymorphs that are produced depend upon factors such as storage temperature, recrystallization solvent, and rate of cooling. Table 2 suggests the importance of polymorphism in the field of pharmaceutics [45],... 

The existence of two polymorphs was reported for a NO-releasing derivative of acetyl-salicylic acid [28]. Selection crystallization of one form or the other was achieved from a number of solvent systems (14 solvents and 3 preparative methods), but several systems were identified that yielded mixtures of the two forms. The single-crystal structure of Form I was reported, but the habit of the Form II crystals precluded their characterization. The transition point of the two forms was calculated from intrinsic dissolution data to be higher than the melting points of both polymorphs and thus the two forms bear a monotropic relationship. 

Crystal polymorphs will usually exhibit different melting points, with the highest melting form being regarded as the most stable. The interconversion of... 

Quantitation of one polymorphic form within another by mid-IR diffuse reflectance has also been performed on SC-41930 [14]. The high melting point form (HM) was spiked with low melting point form (LM) between 0 and 25% w/w. The 1670 cm-1 absorbance feature in the LM was used for quantitation. Based upon the spectral data, a detection limit of approximately 1% w/w of LM in HM was estimated. 

X-ray diffraction studies are usually carried out at room temperature under ambient conditions. It is possible, however, to perform variable-temperature XPD, wherein powder patterns are obtained while the sample is heated or cooled. Such studies are invaluable for identifying thermally induced or subambient phase transitions. Variable-temperature XPD was used to study the solid state properties of lactose [20], Fawcett et al. have developed an instrument that permits simultaneous XPD and differential scanning calorimetry on the same sample [21], The instrument was used to characterize a compound that was capable of existing in two polymorphic forms, whose melting points were 146°C (form II) and 150°C (form I). Form II was heated, and x-ray powder patterns were obtained at room temperature, at 145°C (form II had just started to melt), and at 148°C (Fig. 2 one characteristic peak each of form I and form II are identified). The x-ray pattern obtained at 148°C revealed melting of form II but partial recrystallization of form I. When the sample was cooled to 110°C and reheated to 146°C, only crystalline form I was observed. Through these experiments, the authors established that melting of form II was accompanied by recrystallization of form I. 

In a manner similar to that just described for differential thermal analysis, DSC can be used to obtain useful and characteristic thermal and melting point data for crystal polymorphs or solvate species. This information is of great importance to the pharmaceutical industry since many compounds can crystallize in more than one structural modification, and the FDA is vitally concerned with this possibility. Although the primary means of polymorph or solvate characterization s centered around x-ray diffraction methodology, in suitable situations thermal analysis can be used to advantage. 

A large number of compounds of pharmaceutical interest are capable of being crystallized in either more than one crystal lattice structure (polymorphs), with solvent molecules included in the crystal lattice (solvates), or in crystal lattices that combine the two characteristics (polymorphic solvates) [122,123]. A wide variety of structural explanations can account for the range of observed phenomena, as has been discussed in detail [124,125]. The pharmaceutical implications of polymorphism and solvate formation have been recognized for some time, with solubility, melting point, density, hardness, crystal shape, optical and electrical properties, vapor pressure, and virtually all the thermodynamic properties being known to vary with the differences in physical form [126]. 

Sulfathiazole has been found to crystallize in three distinct polymorphic forms, all of which are kinetically stable in the solid state but two of which are unstable in contact with water [130]. As evident in Fig. 20, the initial intrinsic dissolution rates are different, but as forms I and II convert into form III, the dissolved concentrations converge. Only the dissolution rate of form III was constant during the studies, indicating it to be the thermodynamically stable form at room temperature. Aqueous suspensions of forms I or II were all found to convert into form III over time, supporting the finding of the dissolution studies. Interestingly, around the melting points of the three polymorphs, form I exhibited... 

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