PHAR407: Physicochemical Properties of Drug Molecules

Sample Purity and Chemical Separations

• 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.

Liquid-Liquid Extraction or Solvent Extraction

• 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

Influence of Ionization on Partitioning

• 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

• 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.

Orders 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.