Drug dissolution (log S)

The solubility of drugs in water is of central importance in the process of drug discovery and development, from molecular design to pharmaceutical formulation and biopharmacy because oral absorption is dependent on thecompound dissolving in the aqueous of the gastrointestinal tract (dissolution) and then traversing the actual barrier of the gastrointestinal tract to reach the blood (Smith et al., 2006). Dissolution depends on the surface area of   the   dissolving   solid   and   solubility of the drug at the surface of the dissolving solid. Yalkowsky (1999) has noted that log S correlates well with log P, but with an additional term involving the melting point (mp) for the crystalline solute, it is given as:

Log S = 0.8 - log P - 0.01(mp-25)

Virtually all drugs have aqueous solubilities of log S > -6.

Refrences:

1. Smith QR, Fisher C, Allen DD (2000). Blood-brain barrier: drug delivery and brain        physiology.Proceedings of the OHOLO Conference onBlood-Brain Barrier, 44th, Sept 10-14,2000,Israel. Springer. ISBN: 0306467089. PP. 311-332.

2. Yalkowsky SH (1999). Solubility and solubilizationin aqueous media, Oxford University Press,Oxford. ISBN: 978 084123576 2. PP. 73-104.

Electrostatic Potential Maps

The electrostatic potential map paints the value of the electrostatic potential onto an electron density surface to get a description of the electrostatic characteristics of target drug [1]. By convention, colours toward red depict negative potential, while colours toward blue depict positive potential and colours between depict intermediate values of the potential. Thus, this drug has both, negative and positive well defined regions, which increase the interaction possibilities from the electrostatic point of view. Thus, especially when H-bonding (electrostatic in nature) is involved, the calculation of the electrostatic surfaces can be very useful to visualize the sites of interaction in both hosts and guests to predict their affinities [2]. Analysis of qualitative data obtained by EP calculations also provides useful information for explaining the differential ability of molecular analogs to act with a common receptor. In the present work, electrostatic potential maps were constructed for candidate drugto analyze the characteristics of the electrostatic potential.

References:

1. Abbott N J; (2005), International Congress Series; 1277, 3-18.

2. Hua Gao, V. Shanmugasundaram and Pil Lee, (2002), Pharmaceutical Research; 19(4), 497-503.