Follicular delivery of drugs: Selection of vehicles based on physicochemical approaches

To achieve maximum therapeutic efficacy for treatment of follicular diseases, it is necessary to deliver drugs to the sebaceous follicle. Efficient delivery to sebaceous follicle depends on interaction of drug-vehicle, drug-sebum, and vehicle-sebum. This necessitates a careful selection of appropriate vehicle and subsequently a formulation. In current study, we developed and characterized a model sebum, and consequently used it to identify vehicles that favor the delivery. In an animal model, the potential of these vehicles to deliver the salicylic acid and erythromycin into the sebum filled follicles was examined. The results of these experiments were further extended to investigate the follicular delivery of salicylic acid from oil in water emulsion formulations.; The model sebum shows four major transitions (Mp-1 through Mp-4) between −50°C and 100°C in differential scanning calorimetry analysis. This indicates that at normal skin temperature (32°C), sebum contains both solid and liquid phases. Of these, the former can be a significant barrier to the follicular delivery. The effect of vehicles of different polarities on melting behavior of these solid phases was studied. Among the vehicles tested, hydrophobic vehicles were more effective in lowering Mp-3 while those that lower Mp-4 do not show any particular trend. Follicular delivery of salicylic acid (measured as the extent of preferential deposition into sebaceous glands) dissolved in these vehicles correlated well with its solubility in the respective vehicles. This extent of deposition also showed a relationship with the effect of vehicle on thermal behavior of the model sebum. For erythromycin, however similar relationships were not discernible. It can be concluded that drugs whose follicular delivery depends on solubility, differential scanning calorimetry can be used to identify appropriate vehicles. Further, follicular delivery of salicylic acid from two different types of oil in water emulsions was compared to that using neat vehicle. This research study highlights the role of sebum, its compatibility with drug molecules, and vehicles in the transport of drugs into the follicles. The overall results of these experiments provide a reasonable understanding of the mechanisms underlying the transport of drugs to, and subsequently through the sebaceous follicle.