Dermal and transdermal targeting of dihydroavenanthramide D using enhancer molecules and novel microemulsions

Abstract

Specific accumulation of drugs in certain skin layers or in the blood circulation is the aim of (trans-)dermal targeting. As demonstrated previously, high dermal concentrations of the model drug dihydroavenanthramide D can be reached by the addition of 1,2-alkanediols as penetration enhancer to a conventional o/w cream. The focus of the present study is on an increased permeation by the choice of a modern colloidal drug carrier. Microemulsions based on a vegetable protein surfactant and 1,2-alkanediols as co-surfactant were developed. The respective pseudoternary phase diagrams revealed an increasing area of the optical isotropic phase with increasing chain length of the glycol (C3–C4–C5). Pentylene glycol-containing systems were characterized by electrical conductivity and differential scanning calorimetry indicating the presence of water-continuous microemulsions. Two selected formulations containing pentylene glycol and propylene glycol, respectively, were further investigated by TEM, conductivity, viscosity, and temperature stability. In the subsequently performed Franz type diffusion studies using full thickness human skin dihydroavenanthramide D was applied as model drug. Both formulations showed sufficient penetration into viable skin layers and particularly high permeation rates. Compared to the previously investigated glycol-containing cream, the microemulsions revealed a smaller fraction of the model drug within viable epidermis and dermis, but a strongly increased amount in the acceptor solution. Therefore, the formulations might find different application areas depending on needs concerning localization, beginning and duration of the drug effect.