Solubility, polymorphism

Physical changes in the drug (conversion of a more stable, less readily soluble polymorph, etc.)... 

Crystal form select the most soluble polymorph/anhydrate, if possible, from stability and technical points of view. 

Figure 5. shows the solubility curves for a monotropic system of two polymorphs and will be used to discuss methods for controlling the polymorphic form of the product. In this instance the thermodynamically stable and thus least soluble polymorph is Form I. 

A wide range of physical constants, for instance melting point, boiling point, specific gravity, viscosity, refractive index, solubility, polymorphic forms vis-a-vis particle size, in addition to characteristic absorption features and optical rotation play a vital role in characterization of pharmaceutical chemicals and drug substances. These physical constants will be discussed briefly with typical examples as under ... 

If the chemical contents of a polymorph are different than other forms, it is designated as a pseudopolymorph.Most often this occurs due to the presence of differing amounts of solvent, and may alter physical properties of the crystals such as melting points and solubilities. Polymorphism and pseudopolymorphism may be observed when different experimental conditions are used for synthesis. For example, if crystals are grown by sublimation, changing the temperature will often yield different crystal structures, possibly even metastable phases that are kinetically favored. 

Many compounds form crystals with different molecular arrangements, or polymorphs. These polymorphs may have different physical properties, such as dissolution rate and solubility. The vitamin riboflavin exists in several polymorphic forms, and these have a 20-fold range in aqueous solubility. Polymorphs that have no crystal structure, or amorphic forms, have different physical properties from the crystalline forms. 

Physical instability of liquid formulations involves the formation of precipitates, less-soluble polymorphs, adsorption of the drug substances onto container surfaces, microbial growth, and changes in product appearance. Evaluation of product acceptability is subjective and includes properties such as color, odor, taste, and clarity. Dye stability depends on the... 

Oral liquids Solubility, polymorphic conversions, chirality, excipient interactions, chemical stability, photostability, pH effects, and container interactions (e.g., type III glass). 

An X-T2iy crystallographic study of the a-form of undecasulphur dinitride (S Na) has shown the molecule to consist of two rings, each shaped like the cyclo-octasulphur ring, fused at the 1,3-position and with the bonds from nitrogen coplanar (36). Several properties of the molecule have been studied, namely solubility, polymorphism, enthalpy of formation, and... 

Drug product recall of 60 million tablets of the blood pressure medication Avalide, a combination of two anti-hypertensives, hydrochlorothiazide and irbesartan. Concerns were over possible variability in the amounts of the less soluble polymorph of irbesartan, which may result in slower dissolution. 

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