PH-SOLUBILITY %ionised Acid with pKa 8 100 08010600000000 7 8910111213 PH %ionised 100 Base with pKa 8 000000400000 4 567891011121314 pH
pH-SOLUBILITY SOLUBILITY Acid with Acid with pKa = 8 Base with Base with pKa = 8
Example: Doxorubicin OH pKa2=10.16 9 CCH2OH OH OCH3 H OH pKa3=13.2 CH3 HO NH2 pKa1=8.15
pKa1=8.15 pKa2=10.16 pKa3=13.2 Example: Doxorubicin
Outside Inside pH7.5 pH4.0 BH" BH" B + + H K=B。IH1。 K=[BI[H'] [BH。 [BH'] At equillibrium,if: [B1。=B] Then: [BH'] =H] [BH。 [H。 from slides by Marcel B.Bally
from slides by Marcel B. Bally Marcel B. Bally
pH loading method 300mM CeHgO,3- CcHgO73- Citrate 3H* 3H+ pH3.5 DOX-NHDOX-NH DOX-NH3 pH7.5 from slides by Marcel B. Bally
DOX-NH2 pH 7.5 300mM Citrate pH 3.5 C6H5O73- 3H+ DOX-NH 2 C6H5O7 3- 3H+ DOX-NH3 pH loading method from slides by Marcel B. Marcel B. Bally
1.3.Partition Coefficient and LogP A substance added to a system formed by a mixture of two immiscible liquids will distribute between the two layers.At C1 equilibrium,the ratio of K= concentrations can be defined C2 with the following expression: K=C1/C2 where C1 and C2 are the equilibrium concentrations and K is the partition coefficient. It is defined as the concentration ratio of un-ionized drug distributed between the organic and aqueous phases at equilibrium
1.3. Partition Coefficient and Partition Coefficient and LogP It is defined as the concentration ratio of It is defined as the concentration ratio of un-ionized ionized drug distributed drug distributed between the organic and aqueous phases between the organic and aqueous phases at equilibrium