1. Hemin J Majeed MSc. Pharmaceutical sciences
Physical Pharmacy
Lab 1 - Cosolvency
Hemin J Majeed
MSc. Pharmaceutical sciences

2. Solubility and Dissolution
Dissolution is a criterion by which a solid drug material dissolves in a solvent whereas solubility can be defined as the amount of a solute that dissolves in a particular volume of a solvent
Oral bioavailability is highly dependent on solubility and rate limiting step for some drugs
High solubility feature is not the case with all drug substance
Therefore, several techniques have been used to improve solubility of poor water soluble drugs.

3. Co- solvent effect on solubility
The non-electrolyte and the undissociated molecule of weak electrolyte more soluble in a mixture of solvent than in one solvent alone .this phenomenon is known as co solvency
Co solvent are mixture of water and one or more miscible solvent used to create a solution with the enhance solubility of a poorly water soluble drugs.

4. Characteristics of Cosolvents

5. Widely used co solvents
Glycerine ,PEG,ethyle alcohol and ethyle carbamate

6. Effect of solvent combination on solubility.
Dielectric constant: when applied to solvents, refers to the amount of energy required to separate two oppositely charged bodies in the solvent compared to the energy required to separate the same two oppositely charged bodies in vacuum.
DC of water at 18 C is 78.5 (approx.) it means 78.5 times more energy to separate two oppositely charged bodies in vacuum than in water.

7. DC of solvent changes with:
Temperature: Increasing the Temp. lead to decreasing the DC. why?
Polarity: Increase in polarity cause increasing DC.
EX. Ethanol DC is 26.1 at 18 C ̊ so as %(ethanol/water) increase the DC of the mixture decrease.
The dielectric constant tells us how well the solvent is able to separate ions. Coordination of water molecules around the anion and the cation greatly reduces the ion-ion attraction in the salt.

8. The solubility of the solute is qualitatively related to the DC of the solvent systems.
For example a given solute will have qualitatively similar solubility profile with respect to DC for various Co-solvent combinations.   
Example: this figure shows the solubility of Salicylic acid as a function of a number of solvent systems.
It appear that the magnitude of the solubility varied Considerably in the different co-solvents but the maximum solubility in each case occur at a DC of 15
g % SA
DC 15

9. Experimental work: We will study the effect of solvent combination on the solubility of SA using Ethanol/water co-solvent system. 1. Prepare five conc. of ethanol in water 0%, 10%, 25%, 35%, and 50%. 2. Place 25 ml of each conc. in a conical flask of (50 ml) then adds 0.25 g of SA to each flask. 3. Shake the flasks for 10 minutes. 4. Set aside for 10 minutes to let undisolved SA to settle down, or by filtration process, undisolved SA can be removed from the solution. 5. Withdraw 10 ml of the supernatant and titrate with 0.05N sodium hydroxide solution using phenolphthalin as indicator. 6. The end point is a point when the color changes from yellow to pink. Measure the end points.

10. Calculation: 1 molecule of SA + 1 molecule of NaOH give the product 1 M of SA => 1 M of NaOH 1 eq. SA => 1 eq. NaOH g => 1 L of 1 N NaOH g => 1000 ml of 1 N NaOH 138.1/1000 x 0.05 = 1 ml of 0.05 N NaOH Each 1 ml of 0.05 N NaOH is equivalent to g SA. So End point x = g SA /10 ml Plot the total solubility g/ml SA against %ethanol /water.

11. Thank you