PHYPHAR LAB - EXP 9: Phase Diagram of Ternary Systems Containing Liquid Phases & EXP 10: Distribution of Solutes Between Immiscible Solvents

Cosolvency

One of the most common techniques to deliver water-insoluble drug substances in more acceptable aqueous solutions.

Co-Solvent

Can increase the solubility of a solute in water

Equilateral Tringle Graph or Triangular Diagram

May be used to represent ternary systems

Nernst’s (Partitioning) Law

• At equilibrium, the ratio of concentrations of a solute in two immiscible solvents is constant.

• Ratio of the solute concentration in the organic phase to the aqueous phase

Importance in Drug Absorption

Partition coefficient (K) helps predict drug absorption, distribution, elimination, and biological activity.

Factors Affecting Partitioning

• Ionic Dissociation

• Molecular Association

• Weak Acids/Bases

Ionic Dissociation

Ionized forms of drugs are more soluble in the aqueous phase

Molecular Association

The drug’s solubility profile can change based on its molecular structure

Weak Acids/Bases

Ionization changes depending on pH, altering partitioning behavior

Apparent Partition Coefficient (Kapp)

• Used when the solute is ionized

• Depends on the fraction of unionized drug at a given pH

Formula of Apparent Partition Coefficient (Kapp)

_____ = K x funionized

Shake-Flask Method

• Common method uses 1-octanol and a pH 7.4 buffer as immiscible phases

• Phases are mixed, separated, and drug concentration is measured in the aqueous phase to determine the partition coefficient