PHAYG062 – Preformulation

Solubility: Consolidation questions

The questions below are designed to help you consolidate your learning. If you can answer them
all correctly, then you will do very well in the course. If not, then consult your lecture notes, the
course text (“Essentials of Pharmaceutical Preformulation” by Gaisford and Saunders), or me
(g.williams@ucl.ac.uk)! Please note that there is no obligation to do these questions: they do not
need to be handed in and will not be marked, but they offer you the opportunity to test your
understanding of the material covered.

1. What is meant by the term equilibrium solubility?

2. Explain why the process of dissolution and the melting point of a drug are correlated.

3. Write an expression for the ideal solubility of a drug.

4. The melting point of diclofenac is 170.7 °C, and its heat of fusion is 18.95 kJ mol-1. Calculate the
ideal solubility (in terms of mol fraction) at (a) 25.0 °C; (b) 50.0 °C; and, (c) 74.01 °C.

5. In water, diclofenac is found to have a solubility of 2.37 mg/L. Comment on this given your
answer to Q4.

6. An experimental drug is found to have a melting point of 237 °C, and a heat of fusion of 33.67
kJ mol-1. Calculate the ideal solubility (in terms of mol fraction) at (a) 22.5 °C; (b) 25.0 °C; and,
(c) 79.10 °C.

7. Explain the factors which cause experimental solubility to deviate from the ideal value.

8. State the Henderson-Hasselbalch equation for acidic and basic drugs.

9. Sketch a plot to show how the solubility of an acidic drug will change with pH.

10. A basic drug B with pKa = 6.79 is found to have an intrinsic solubility of 3.45 mg mL-1. Calculate
the total solubility at (a) pH 1.7; (b) pH 3.44; (c) pH 4.59; and, (d) pH 11.2.

11. An acidic drug A with pKa = 4.33 is found to have an intrinsic solubility of 22.06 mg mL-1.
Calculate the total solubility at (a) pH 2.08; (b) pH 6.88; (c) pH 5.89; and, (d) pH 7.47.
12. Comment on how the variation in solubility of ionisable drugs with pH influences their
behaviour in drug delivery systems.

13. State the Noyes-Whitney-Nernst-Brunner equation.

14. Using your answer to Q13, explain how the dissolution rate for a tablet of drug D will be
affected by (a) doubling the surface area of the tablet; (b) reducing the thickness of the
boundary layer.

15. State the advantages and disadvantages of dissolution testing.

16. Explain what is meant by the term “sink conditions” and detail why it is important to use skink
conditions in dissolution testing.