Factors Influencing the Solubility of Drugs: Labs

Laboratory Procedure

1. Determination the solubility of salicylic acid at pH = 3 and pH = 4.5 at 25°C.

You will determine the concentration of salicylate in each solution by a spectrophotometric analysis. Thus we can determine salicylate concentration readings of the pH 3 and 4.5 solutions by comparing spectrophotometric measurements from those solutions to standards of known concentration. Since each of these solutions (at pH 3 and 4.5) is saturated, then measurement of their concentration gives us the solubility of the compound at each pH.

(NOTE: The saturated solutions may contain considerable precipitate and should be filtered or carefully decanted to avoid getting solid particles in your sample.)

 View a video demonstration on how to filter a solution

Equation of Beer’s Law Plot (attach graph):

Calculate the solubility of salicylic acid at the two pHs:

2. Determination of pHp

In this exercise you will determine the pH at which the solubility of the undissociated species is exceeded and the drug begins to precipitate from solution.

• Prepare 100 ml of a 4.5% sodium benzoate solution and transfer to an Erlenmeyer flask. Determine the pH using a pH meter. Add 2.0 N HCl dropwise, swirling continuously and stopping when turbidity (cloudiness) occurs. Record the pH of the final solution. Now compare the experimentally determined pHp with the expected pHp value calculated in your pre-lab data.
• Prepare 100 ml of a 1.5% solution of Procaine HCl and transfer to an Erlenmeyer flask. Determine the pH using a pH meter. Add 2.0 N NaOH dropwise, swirling continuously until precipitation occurs. Record the pH of the final solution. Now compare the experimentally determined pHp with the expected pHp value calculated in your pre-lab data.

    Benzoic Acid Ka (@ 25°C) _____________

    Benzoic Acid pKa ____________

    Benzoic Acid molecular weight _____________

    Sodium Benzoate molecular weight ____________

    Benzoic Acid solubility @ 25°C (S_o) _________ g/L = ______ mole/L

    Procaine Kb (@ 25°C) _____________

    Procaine pKb__________

    Procaine molecular weight_____________

    Procaine HCl molecular weight_____________

    Procaine solubility @ 25°C (S_o)_________ g/L = ______ mole/L

    Determine the pH of the final solution.

 View a video demonstration on how to use a pH meter

Theoretical Determination of pHp

Using the pHp equations, calculate the expected or theoretical pHp for:

     the 4.5% Sodium Benzoate solution

     the 1.5% Procaine HCl solution

Experimental Determination of pHp

pHp of 4.5% Sodium Benzoate

• Initial pH ________________
• Final pH (pHp) ________________

pHp of 1.5% Procaine HCl

• Initial pH ________________
• Final pH (pHp) ________________

3. Formulation of a cosolvent system using dielectric constant

Determine the percentage (v/v) of ethanol required to maintain terpin hydrate 10 mg/ml in solution.

• Make 10 ml of solutions containing 20, 30, 40, 50, 60, 70 and 80% ethanol and 100 mg of terpin hydrate. Prepare 20 ml of a stock solution that is 50 mg/ml of terpin hydrate in Alcohol USP. Add 2 ml of the stock solution to each scintillation vial. Then add the remainder of the required Alcohol USP, and then the appropriate volume of water.
• Refrigerate the solutions overnight and determine the smallest percentage of ethanol required to keep the terpin hydrate in solution by observing the solutions for precipitation.

Calculations for Ethanol using Alcohol, USP (95% ethanol)

Indicate precipitation presence with a “+” and precipitation absence with a “-“.

Calculate the dielectric constant δ needed to solubilize terpin hydrate at a concentration of 10 mg/ml using the following equation:

     (Vol. fraction H₂0)(δ H₂0) + (Vol. fraction ETOH)(δ ETOH)