The influence of topical formulations on the permeation of 5-aminolevulinic acid and its n-butyl ester through excised human stratum corneum

Abstract

The limited permeation of 5-aminolevulinic acid (ALA) through excised human stratum corneum could be improved by using 5-aminolevulinic acid- n-butyl ester (ABE). Furthermore drug permeation could be increased by choice of a permeation enhancing formulation. In this study, permeation of ALA and ABE was investigated from various formulations. In addition, differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD) experiments were performed in order to reveal an interaction between the tested formulations and stratum corneum lipid structure. Drug incorporation into Dolgit ® Mikrogel showed the highest increase in permeability with both ALA and ABE. Especially, ABE together with Dolgit ® Mikrogel was the most promising combination. Further permeation studies with poloxamer based ABE formulations, partially enriched with ibuprofen acid and medium chained triglycerides showed that both compounds promote permeation. The permeation coefficients of either drug from Excipial ® Creme and Basiscreme DAC were found to be very similar. These results were in accordance with those of DSC and WAXD experiments. Interaction between formulation and stratum corneum lipid structure resulting in an increased drug permeation only occurred after pretreatment with formulations enriched with ibuprofen acid. After pretreatment with Excipial ® Creme, Basiscreme DAC or Excipial ® Fettcreme stratum corneum structure and subsequently permeability remained unchanged. Nevertheless permeation of ALA from Excipial ® Fettcreme is slower than from the tested hydrophilic formulations and therefore believed to be influenced by the affinity of ALA to the vehicle and stratum corneum.