Typically special dosage forms are required to overcome the biopharmaceutic challenges of drug molecules. For example modified/extended/controlled release oral dosage forms are formulated for drugs with a short half-life so that the frequency of administration can be reduced and thereby improving patient adherence. In addition, special dosage forms can also attenuate fluctuations in the plasma drug levels (smaller peaks and troughs) to improve efficacy and minimize side effects

a) A once a day extended/modified release dosage form was developed for a drug with a half life (t1/2) = 0.5 hr and this drug is mainly absorbed through the small intestine. However the dosage form failed to sustain the plasma drug level. Assuming the dosage form was functioning properly and the release could last for 24 hours, please provide a possible explanation for this phenomenon. (3 marks)

b) A modified/extended/slow release dosage form usually exhibits flip-flip pharmacokinetics. Please define flip-flop pharmacokinetics (3 marks)

c) Please explain how a modified/extended/slow release oral dosage form can achieve flip-flop pharmacokinetics (3 marks)

d) Is it possible for flip-flop pharmacokinetics to exist after IV administration of drugs? Why? (3 marks)

e) Please provide one other example of dosage form that give rise to flip-flop pharmacokinetics (3 marks)