Optimization of bioavailability of topical steroids: thermodynamic control.

In theory, under strictly defined ideal conditions, the bioavailability of a drug from a topical formulation should depend only on the thermodynamic activity of the medicament in the base. We tested this fundamental postulate using a steroid as the test drug, formulated in a series of solutions and gels at 90% saturation, i.e., ideally at constant thermodynamic activity. The in vivo assessment method was the occluded vasoconstrictor test in humans. For most systems, this simple measure of thermodynamic activity correlated with drug bioavailability as assessed by the blanching response. Where there were differences, we have rationalized them in terms of penetration enhancement, irritancy, dehydration of the stratum corneum, or steroid binding in the base, although such factors have not been explicitly demonstrated.