ANYL 60 |
| Ionization constant, pKa, and distribution coefficient, log D, are two important physicochemical properties for any ionizable pharmaceutical drug. While the octanol–water partitioning system is most commonly employed in medicinal chemistry, there is an increasing interest in liposome–water partitioning, since phospholipid liposomes are much better mimics of a cell membrane than octanol. In this poster, we will discuss the determination of distribution/partition coefficients by (i) derivative spectrophotometry and compare its results with (ii) the potentiometric method based on changes in the apparent pKa of a drug in the presence of liposomes as the partitioning medium.
Unlike absorbance, the second derivative intensity is insensitive towards light scattering and can be used to deduce the fractions of a drug that partitions following the addition of increasing amounts of phospholipid to an aqueous buffer solution of the drug. At lmax, the change in second derivative Dd gives rise to a hyperbolic curve as a function of lipid concentration [L]. With the known molar volume (gL) of the phospholipid, curve fitting to the theoretical equation 1 provides the distribution coefficient D for the drug. The figure shows the results for propranolol together with a lipophilicity profile (plot of log D vs. pH).
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General Papers
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster
Division of Analytical Chemistry |
