Effect of formulation on the topical delivery of alpha-tocopherol.

The objective of this research was to investigate the effect of concentration and delivery system on skin permeation of alpha-tocopherol (alpha-T). Also, the addition of sunscreens and oleic acid on alpha-T permeation was studied using an in vitro micro-Yucatan pig skin model. Various delivery systems of alpha-T (1%) were formulated, which included simple solution, gels, emulsions, and microemulsions. The experimental design chosen for this study was a statistical randomized complete block design. alpha-T delivery was proportional to its concentration. The hydroalcoholic gel delivered significantly higher amounts of alpha-T into the receptor than the other gels used. A microemulsion containing isopropyl myristate emerged as the best delivery system for alpha-T among all the systems studied. Pig skin is a suitable in vitro model for studying the permeation of alpha-T and possibly other antioxidants, though in vivo experiments in humans are required to further corroborate the data.

Influence of vehicles on the phase transitions of model sebum.

It is hypothesized that vehicles that are miscible with sebum may concentrate drugs in the sebaceous follicle. This is important for the treatment of diseases like alopecia and acne. The main objective of the study was to identify different vehicles that affect the thermal behavior of sebum using differential scanning calorimetry (DSC). For this purpose, a model sebum mixture was prepared based on a composition reported in the literature. The test vehicle was added in a concentration of 15% of the weight of the sebum. Small portions of the above mixture were put in a pre-weighed DSC pan. These were run from -50 to 100 degrees C at 5 degrees C/minute. In the model sebum, four distinct transitions were observed: Mp-1 and Mp-2 occurred below 0 degrees C while Mp-3 and Mp-4 occurred above 30 degrees C. Vehicles that affected Mp-3 and Mp-4 were considered for further analysis. From the vehicles tested it was found that the hydrophobic materials were more effective in lowering Mp-3, while the ones that affected Mp-4 did not show any particular trend. Some of the vehicles tested are known skin permeation enhancers, and it is proposed that they interact with sebum and increase permeation by the follicular route. It was found that DSC may be used to identify vehicles that are miscible with sebum and that may deliver drugs preferentially to the sebaceous follicle.

Investigation of nail permeation enhancement by chemical modification using water as a probe.

Our objective was to screen molecules that could interact with keratin in the human nail and thereby improve the topical penetration of actives into and through the nail plate. We used specialized Franz-type diffusion cells for our permeation experiments and water as a marker molecule. Aqueous/hydroalcoholic gels containing the enhancers were spiked with tritiated water and compared with a control (without enhancer). We computed the normalized water flux (defined as a product of flux and nail thickness) for each gel. We defined an enhancement factor for water as the ratio of the normalized water flux from a gel containing enhancer to that of the control. Our results indicate that the chemical structure of the modifier is most important in determining its ability to enhance penetration. The best enhancement effect was obtained using N-(2-mercaptopropionyl) glycine, a mercaptan derivative of an amino acid, in combination with urea. The concentration of each chemical modifier was linearly related to normalized water flux and mercaptan levels were more important that urea levels in penetration enhancement. Barrier integrity of nails was compromised after treatment with effective chemical modifiers. Thus, we have developed a suitable technique to screen nail penetration enhancers using water as a probe.