Solvate Formation

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... 

An experimental note of Ref. 1 only vaguely suggests possible solvate formation ... 

In the disc method, the powder is compressed by a punch in a die to produce a compacted disc, or tablet. The disc, with one face exposed, is then rotated at a constant speed without wobble in the dissolution medium. For this purpose the disc may be placed in a holder, such as the Wood et al. [Ill] apparatus, or may be left in the die [112]. The dissolution rate, dmldt, is determined as in a batch method, while the wetted surface area is simply the area of the disc exposed to the dissolution medium. The powder x-ray diffraction patterns of the solid after compaction and of the residual solid after dissolution should be compared with that of the original powder to test for possible phase changes during compaction or dissolution. Such phase changes would include polymorphism, solvate formation, or crystallization of an amorphous solid [113],... 

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]. 

The above-mentioned on-line spectroscopic techniques have involved granulation monitoring for particle size assessments and end-point control however there are other concerns involved with wet granulation which include polymorphic transformations or solvate formation that can affect end product quality. ... 

Figure 14. 2SNa chemical shift data for Nal in H20-ethyl-enediamine (en) (45). — theoretical curve (Equation 74) with n = 4, K = 2.3, k = 0.8. The asymmetry occurs at the wrong end to account for by bidentate solvate formation by ethylenediamine... 

Metered-Dose Inhalation Aerosols Quantity of delivered dose, total number of acceptable doses delivered, color, solvate formation with propellant, particle size distribution, weight loss of canister (i.e., loss of propellant), pressure, valve corrosion, and storage in both upright and inverted positions. 

In these centres, the negative charge is concentrated on the heteroatom. The centre-counter-ion interaction is much stronger than with carbanion centres. This is manifested by a tendency to aggregate and solvate formation. The reactivity of this kind of ion pair may exceed the reactivity of free ions, due to the unequal contribution of the desolvating energies of ion pairs and free ions [103],... 

This relation holds only if both saturated solutions are in equilibrium with the same solid phase. Solvate formation in one and/or the other medium necessitates a correction ... 

A large proportion of drug substances, whether neutral molecules, free adds, free bases or salts, are capable of exhibiting polymorphism or pseudopolymorphism (hydrate or solvate formation). It has been reported that 70% of barbiturates, 60% of sulfonamides and 23% of steroids exhibit polymorphism." Polymorphism often influences a range of physicochemical properties such as solubility, dissolution rate, stability and powder properties as well as bioavailability. Usually, it is possible to determine the most stable polymorph and discover recrystallization solvents that uniquely produce this form and improve the physicochemical and physicome-chanical properties and chemical stability of the drug. 

Hydrates or solvates of a drug substance, similar to polymorphs, are crystal modifications of a drug substance. This characteristic of solvate formation is sometimes known as pseudomorphism. The water of crystallization in hydrates and the organic solvent in solvates are incorporated with the drug molecule to form a unique structure. 

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