PHAR407: Physicochemical Properties of Drug Molecules

Study Notes

Many chemical analyses are not specific for one compound and respond to many potential interferences in the sample.
It is often necessary to first purify the compound of interest by removing interfering substances before a selective analysis is possible.
Techniques available for chemical separations include extraction, distillation, precipitation, chromatography, centrifugation, filtration, and others.

Diethyl ether, toluene, and hexane are common solvents that are immiscible with water, less dense than water, and form a separate phase that floats on top of the aqueous phase.
Chloroform, dichloromethane, and carbon tetrachloride are common solvents that are denser than water.
The distribution coefficient (K) is used to describe the ratio of the concentration of a compound in the organic phase to its concentration in the aqueous phase.
Formulae used in extraction:
- q = fraction of compound remaining in aqueous phase = naq/nt
- p = fraction of compound extracted to organic phase = norg/nt
- q + p = 1
- q and p after single extraction can be determined by the formulae:
  - q = KVR + 1
  - p = 1 / (KVR + 1)
- % remaining in aqueous phase = qx100
- % extracted = px100
- After multiple (n) extractions, the formula: qn = (1 / (KVR + 1))^n is used

The ability to change the distribution ratio of a weak acid or weak base with pH is useful in selecting conditions that will extract some compounds but not others.
Use low pH to extract HA but not BH+ (weak acid extractions)
Use high pH to extract B but not A- (weak base extractions)

Chemical kinetics is concerned with the rate of chemical reactions and the mechanism by which they proceed.
The rate of chemical reaction (its velocity or speed) is the number of moles transferred from reactant to product in unit time.
The rate law shows how the rate of a reaction depends on concentrations of various species in the reaction.
The rate constant (k) is a measure of the rate of reaction.

Zero-order reaction: the reaction rate is constant and independent of the concentration of the reactant.
First-order reaction: the rate of reaction depends on the concentration of the reactant.
Second-order reaction: the rate of reaction depends on the concentration of the reactant squared.
Third-order reaction: the rate of reaction depends on the concentration of the reactant cubed.
Determination of the order of reaction can be done numerically or graphically.