The Pharmaceutics and Compounding Laboratory
Extraction of Drugs

Different Aggregation State

Most of the compounds encountered in pharmaceutical analysis are weak acids or bases and their solubility characteristics depend upon their ionic form (molecular species being more soluble in nonpolar, organic solvents and the ionic species being more soluble in polar especially aqueous solvents). Neutral or unionized compounds can be extracted from aqueous solutions while ions cannot. When a drug exists in its ionized form, it can be converted to the unionized form by altering the pH of the medium in which the drug is contained.

  1. Partition coefficient as a function of pH

    Many drugs are acids or bases that dissociate in aqueous solution. Changing the pH of the aqueous solution alters the ratio between the ionized and unionized form of the drugs. Since it is the unionized form which is extracted into the organic phase, the fraction extracted will vary with pH of the aqueous solution.

    In aqueous buffer:

    The partition between organic and aqueous buffer can be described by a "true" partition coefficient, PC, as:

    In lab you will be measuring an apparent partition coefficient, PC', which will vary with pH or [H3O+]. This apparent partition coefficient is given by

  2. The partition coefficient and pKa determination

    It is possible to determine the pKa of the drug undergoing extraction using the data generated in part B.1.

    Using the equation:

    and substituting PC.[HA]org for [HA]org and Ka[HA]aq/[H3O+] for [A-]aq, gives the following equation:

    which simplifies to

    This gives us an equation with PC' as function of [H3O+] with two unknown parameters, PC and Ka. This can be converted into a straight line equation by taking the reciprocal of both sides of the equation.

    Thus:

    or

    Therefore plotting 1/PC' versus 1/[H3O+] should give a straight line with a slope of Ka/PC and an intercept of 1/PC.