Physicochemical characterization aqueous solubility

It is important to characterize the physicochemical properties of the suspensions well, so that the PK data can be interpreted appropriately. Typical characterization of the drug substance includes purity, residual solvents, aqueous solubility pro Lie (pH 2, FaSSIF), crystallinity (XRPD/DSC), particle size, pl and logP. For solution formulations at various stages of discovery studies, dose analysis is essential, and for efLcacy assessment and toxicology studies, chemical stability for the... 

Poly(N-isopropylacrylamide) (polyNIPAAM), formed by a free radical polymerization of N-isopropylacrylamide, is a water soluble, temperature sensitive polymer. In aqueous solution, it exhibits a lower critical solution temperature (LCST) in the range of 30-35 C depending on the concentration and the chain length of the polymer. Thus, as the solution temperature is raised above the LCST, the polymer undergoes a reversible phase transition characterized by the separation of a solid phase which redissolves when the solution temperature is lowered below the LCST. Its physicochemical properties have been investigated by several laboratories (1-3). 

One of the benefits of the methods discussed in this chapter is that they provide a complete characterization of the thermodynamics of transfer of solute from crystal to aqueous solution. Since the solubility of a crystalline solute depends upon the properties of the undissolved crystalline precipitate as weU as the properties of the solution, the thermodynamic data provides valuable information in understanding not only which of the two molecules is more soluble but also why the selected molecule is more soluble. By contrast, QSPR models, which are statistical rather than first-principles approaches, provide only limited statistical information about the underlying physicochemical processes. Moreover, since most QSPR models predict solubility from molecular rather than crystal structure, they are not able to rationalize or predict different solubilities for different polymorphs of a molecule. Therefore, we believe that the bottom-up methods that utilize efficiently molecular-scale information about the solute and solvent structure will attract more attention in the future in terms of both practical applications and fundamental studies of solubility of druglike molecules. 

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