Follicular (pilosebaceous unit) deposition and pharmacological behavior of cimetidine as a function of formulation.

The effect of formulation on cimetidine delivery to the pilosebaceous unit and other skin phases was studied. In vitro and in vivo deposition determinations as well as a pharmacodynamic antiandrogenic sebaceous gland bioassays were made. A complex variety of factors influence how the formulation affects both the degree of drug deposition and its pharmacological activity in the pilosebaceous unit. When cimetidine was applied in formulations at pH values where it was predominately unionized, the thermodynamic driving force proved the dominant factor in influencing the extent of drug deposition into the pilosebaceous unit. Although more cimetidine was deposited into the pilosebaceous unit in vivo from the phospholipid-based liposomal formulation when cimetidine was ionized, this formulation was also the only one devoid of significant antiandrogenic action. Of great importance, it is clear from the studies that deposition from complex formulations, such as liposomes, where bilayer/drug interactions can persist in the skin, may give a false impression of the activity of a drug within a tissue. Moreover, data for cimetidine in 50% alcohol solution show that one can maintain local effects while reducing systemic activity by simply manipulating drug concentration in the application.