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Solvent-mediated phase transformation

The phenomenon of pseudopolymorphism is also observed, i.e., compounds can crystallize with one or more molecules of solvent in the crystal lattice. Conversion from solvated to nonsolvated, or hydrate to anhydrous, and vice versa, can lead to changes in solid-state properties. For example, a moisture-mediated phase transformation of carbamazepine to the dihydrate has been reported to be responsible for whisker growth on the surface of tablets. The effect can be retarded by the inclusion of Polyoxamer 184 in the tablet formulation [61]. [Pg.153]

H. Qu, M. Louhi-Kultanen, J. Rantanen and J. Kallas, Solvent-mediated phase transformation kinetics of an anhy-drate/hydrate system, Cryst. Growth Des., 6, 2053-2060 (2006). [Pg.241]

Davey, R.J. Cardew, P.T. Mcewan, D. Sadler, D.E. Rate controlling processes in solvent-mediated phase-transformations. J. Cryst. Growth 1986, 79 (1-3), 648-653. [Pg.854]

Murphy, D. The Solvent-Mediated Phase Transformation of Carbamazepine and the Influence of Surfactants on the 153. Nucleation Mechanism and Crystal Morphology. Ph.D. thesis. The University of Michigan Ann Arbor, MI, 1997. Rodriguez-Homedo, N. Murphy, D. Surfactant-facihtated crystallization of dihydrate carlramazepine during dissolution of anhydrous polymorph. J. Pharm. Sci. 2004, 95 (2),... [Pg.857]

It is important to note that the solubility of the drug in these organic sol-vent/water mixtures must be high enough to facilitate phase transformation. The factors that determine the kinetics of solvent mediated phase transformations are discussed in more detail in subsequent sections of this chapter. [Pg.60]

The kinetics for a solvent mediated phase transformation will be governed by the kinetics of dissolution, nucleation, and crystal growth. These rates will depend directly on the solvent and any step may be rate limiting. As discussed in earlier sections of this chapter, the solvent influences the nucleation rate and crystal growth rate via two factors 1) solute solubility and 2) specific solvent-solute interactions. The dissolution rate will also be solvent dependent as pharmaceutical materials generally exhibit a wide range of dissolution rates in different solvents. [Pg.76]

Cardew PT and Davey ly. The Kinetics of Solvent-Mediated Phase Transformations. Proc R Soc Lond 1985 A398 415-428. [Pg.103]

Davey ly, Cardew PT, Mcewan D, and Sadler DE. Rate Controlling Processes in Solvent-Mediated Phase Transformations./Cryst Growth 1986 79 648—653. [Pg.104]

One way of assessing whether the solid is a metastable form of the compound is to slurry the compound in a range of solvents. In this way, a solvent-mediated phase transformation maybe detected using the usual techniques (Davey et al. 1986). [Pg.43]

Due to the differences in melting point and other characteristics of polymorphs, solubility differences are often observed. Usually the most stable form of the compound has the lowest solubility in any solvent. It has already been noted that solids can undergo phase changes by way of the solution phase (Davey et al. 1986). When the solvent is in contact with the metastable phase, it dissolves, and the stable phase nucleates and grows from solution. So it is always worth slurrying a compound and assessing the solid phase to determine whether a solution mediated phase transformation to the stable phase has taken place. [Pg.81]

Davey, R. J., R T. Cardew, D. McEwan, and D. E. Sadler. 1986. Rate processes in solvent-mediated phase transformations./. Cryst. Growth 79 648-653. [Pg.90]

The various crystal modifications of a substance will possess different melting points and thereby have different solubilities (Brittain, 2002). Only one solid phase is thermodynamically stable for a given set of environmental conditions. The most stable form has the lowest free energy and therefore the lowest solubility. Metastable forms can theoretically be used to improve solubility, but the kinetics of the transformation back to the stable crystal modification must then be taken into account. In suspension, solvent-mediated transition is generally too rapid to give a product with an acceptable shelf-life. In solid dosage forms, it may be possible, however, to utilize a less stable crystal modification. Due to the decreased molecular mobility in the solid state the transition rate can be low. [Pg.353]

Clearly, one can consider a wet granulation to be equivalent to a suspension of the drug entity in a mixture of solvent and excipients. Since the usual solvent is water, one can encounter a variety of interconversions between anhydrates and hydrates, or between hydrates and hydrates, which are mediated by the presence of the solvent. It is equally clear that one should not expect to be able to wet-granulate the metastable phase of a particular compound if that metastable phase is capable of transforming into a more stable form. A discussion of solvent-mediated phase transformations has been given in an earlier chapter and need not be repeated here. [Pg.340]

Theoretical and experimental studies of the role of solvent on polymorphic crystallization and phase transformations abound in the literature of the last few years and some pertinent examples are described here. For solvent-mediated transformations, the driving force is the difference in solubility between different polymorphs. An important earlier paper on the kinetics of such phase transformations [51 ] described a model featuring two kinetic processes in sohd to solid phase changes via a solution phase, namely dissolution of the metastable phase and growth of the stable one. [Pg.169]

This type of behaviour is not confined to polymorphs but may extend to pseudopolymorphic forms such as hydrates and solvates. A recent case of solvent-mediated phase transformation involved polymorphic and pseudopolymorphic forms of thiazole carboxylic acid [55], where the transformation is again sensitive to the composition of the mixed solvent. Three forms of the compound are known, an anhydrous form, a 0.5 hydrate, and a 1.5 hydrate. In 50-80% solutions (% = vol.% MeOH-H20), transformation of the 1.5 hydrate to the 0.5 hydrate was observed while transformation to the anhydrous form occurred in 85-100% solutions. No transformation occurred in 0-30% solutions. Detailed study of a solvent-mediated polymorphic transition has also been carried out for the antiulcerative agent cimetidine [56] for which seven polymorphic forms are known. An important feature of this study was the systematic use of seed crystals to induce crystallization at different supersaturation ratios. [Pg.170]

Phase transformations can also occur in the solid state, and this mode is particularly common in organic solids held close to their melting point. The roles of both solid-state and solvent-mediated polymorphic transformations have been studied with ammonium nitrate by Davey, Guy and Ruddick (1985) and with oleic acid by Suzuki, Ogaki and Sato (1985). [Pg.284]

Cardew, P.T. and Davey, R.J. (1985) The kinetics of solvent-mediated phase transformations. Proceedings of the Royal Society, A398, 415-428. [Pg.541]


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See also in sourсe #XX -- [ Pg.20 , Pg.27 , Pg.192 , Pg.208 , Pg.264 , Pg.268 , Pg.282 ]




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