EFFECT OF COLLAGEN MICROPARTICLES ON THE STABILITY OF RETINOL AND ITSABSORPTION INTO HAIRLESS MOUSE SKIN IN-VITRO

Collagen microparticles (CMPs) were manufactured with the objective to enhance the dermal delivery of all-trans retinol. The influence of CM Ps on the stability of retinol was investigated after a long-term stor age of two hydrogel preparations (hydroxyethylcellulose). The retinol in the first preparation was adsorbed onto the surface of CMPs, wherea s the retinol in the second preparation was freshly precipitated. Reti nol was not protected from oxidization by adsorption to CMPs. However, the sorption on the surface of CMPs prevented the retinol from crysta llization. On the other hand, significant crystallization occurred wit h the freshly precipitated retinol. For the study of the in vitro pene tration of retinol into hairless mouse skin three preparations for top ical application were used. Beside the two hydrogel preparations menti oned above, an O/W-creme was tested. The study of the in vitro penetra tion was performed by using Franz diffusion cells and tritium labelled retinol. Both hydrogel preparations yielded significantly higher quan tities of penetrated retinol than the O/W-creme. The amounts of radioa ctive retinol in the stratum corneum and in the epidermis and dermis w ere in all cases more than ten times higher for the hydrogel preparati ons. The other remarkable result was that the presence of CMPs led to a faster and higher transport of retinol into the skin than the freshl y precipitated drug. With the CMP preparation a statistically signific ant increase of penetrated retinol was found during the first 4 h afte r application in the stratum corneum. In the residual epidermis and de rmis a clear tendency towards enhanced quantities of penetrated retino l also were observed with the CMPs compared to the freshly precipitate d drug in the hydrogel.