1. Lab. VIII Partition Coefficient By Pharmacist Muhanad S. AL-Ani

2. Lab. VIII Partition Coefficient A solute dissolved in one phase immiscible with other phase at equilibrium will be distributed between the two phases so that the ratio of the concentrations in the two phases is a constant at given temperature. This constant referred to as the distribution constant or partition coefficient K=Cu/CL C U and C L : are the concentrations in the upper and lower layer.

3. It is one method of analysis used to determine the complex formation and to study the stability constant. In most procedures of pharmacy it is desired in extraction or removal of a particular solute from a heterogeneous system.

4. At equilibrium the fraction of the solute found in the upper layer is equal to: U = K r / K r +1 K: is the partition coefficient r : is the ratio of volumes of the upper layer to the lower layer. At equilibrium the fraction of the solute found in the lower layer is equal to: L = 1 / K r + 1

5. If the lower is re-extracted with successive equal volumes of the upper layer. Each extract will contain Un of the solute. U n = K r / (K r + 1) n L n = 1 / (K r/n + 1) n More exhaustive extraction is obtained by using a given volume in several portions than in a single extraction,

6. Example: A liter of an aqueous solution of a drug to be extracted by using a liter of ether, the partition coefficient is 2. If the liter of ether is divided into four 250 ml, portions, a larger fraction of the drug will be extracted then by a single extraction. L = 1 / (2x1) + 1 = 0.333 The fraction of the drug remaining in the lower phase after the fourth extraction is: L4 = 1 / (2x1/4 + 1) 4 L 4 = 0.197 In this case the same volume of the ether used in four portions extracts 20% more than in a single extraction.

7. In extraction from solids equilibrium: 1.Proceeds very slowly so extraction is not usually carried out under equilibrium conditions. The use of proper solvent and the additions of other substances to improve extraction is more important. 2. Also it is necessary to extract some interfering substances such as wax or gum by a solvent in which the desired solute is insoluble,

8. Partition is significant in pharmaceutical dosage forms, for example in oily base suppository which melt at body temp. the release of the drug depends on the form of the drug and its partition coefficient. If the drug has a high partition coefficient favoring the oil phase, it will be slowly released and perhaps not rapidly enough to provide a concentration required for the therapeutic effect.

9. Experiment: Calculation of partition coefficient of iodine between water and chloroform. Procedure: 1.Add 20 ml of 1% iodine solution in chloroform to a dry conical flask. 2. Add 50 ml of DW to the flask. 3. Thoroughly shake the flask for 1/2 hr then allow standing for complete phase separation, this need another 1/2 hr. 4. Withdraw 10 ml from the upper aqueous layer and titrate against 0.02 N sodium thiosulfate (end point is the disappearance of the pink color).

10. 5. Withdraw 5 ml from the lower organic layer, the inside wall of the pipette must be kept dry as it pass through the aqueous phase by placing the finger tightly over the upper end of pipette. 6. Add 5 ml of 10% KI to this 5 ml of the organic layer to facilitate its extraction from the organic layer and facilitate its titration with 0.1 N aqueous sodium thiosulfate solution. (end point is the disappearance of the pink color).

11. Calculation: Conc. of iodine in water = V x N (0.02) / 10 Conc. of iodine in chloroform = V x N (0.1) / 5 K = Conc. of iodine in water / Conc. of iodine in chloroform