1. SOLUBILITY AND DISTRIBUTION

2. Molecular Interactions Ionic interactions Dipole-dipole interactions Induced dipoles Hydrogen bond + - -+-+ +-+- + -

3. Water Miscibility Solvents with relatively high polarity are miscible in water (e.g. acetic acid, ethanol, dioxane, DMSO). Solvent with low polarity or non-polar are water-immiscible (hexane, petroleum ether) Ask your advisor for the Solvent Miscibility Table Ask your advisor for the Solvent Miscibility Table

4. Solvent - Solute Interactions Polar solvents (e.g., water): (1) owing to high dielectric constant reduce ionic attraction between oppositely charged ions in crystals; (2) break covalent bonds of strong electrolytes resulting in dissociation; (3) solvate molecules through dipole interaction forces (particularly, hydrogen bond). Nonpolar solvents (e.g. hydrocarbons): dissolve nonpolar compounds through induced dipole interactions. Semipolar solvents (ketones, alcohols): can induce polarity in nonpolar solvent molecules (co-solvents).

5. Solvent Polarity

6. Liquid-Liquid Systems Miscibility: polar and semipolar solvents (e.g. water and alcohol, glycerin and alcohol, alcohol and acetone) are completely miscible in all proportions. Partial miscibility: With certain proportions two liquid layers are formed (e.g., water-ether, phenol-water) Miscibility is characterized by the phase diagram. A 100% A 100% B 100% C B C Miscible LPS

7. Effects on Solubility Pressure: increases solubility of gases (Henry’s law: P B = P B o.  A x B ) Temperature: solubilty of most gases decreases, solubility of liquids and solids may be affected both ways Co-solvents: increase solubility by changing the solvent polarity. Salting out: elaboration of gases from solutions by electrolytes (NaCl) and highly polar nonelectrolytes (glucose)

8. Doxorubicin and Taxol Doxorubicin Taxol

9. Cyclodextrin

10. More Drugs Aspirin Erythromycin Bactrim (sulfamethoxazole) AZT (Zudovudine) Acyclovir (Zovirax)

11. Even More Drugs Ibuprofen (Advil) Lavimudine (3TC) Acetaminophen (Paracetamol) Retinol (Vitamin A) Vitamin B 12

12. Solubility of Acids/Bases HA sold = HA solution HA solution + H 2 O = H 3 O + + A - [HA solution ] = s o ; Solubility: s = s o + [A - ] s soso pKapKa 2so2so pH