Double emulsions based on silicone-fluorocarbon-water and their skin penetration.

Double emulsions have significant potential in pharmacy and cosmetics due to the feasibility of combining incompatible substances in one product and the protection of sensitive compounds by incorporating them into their innermost phase. However, a major drawback of double emulsions is their thermodynamic instability and their strong tendency to coalesce. In the present study, the physicochemical stability, the skin permeation and the skin penetration potential of modified semi-solid double emulsions was investigated. The double emulsions were prepared of the cosmetically applied perfluoropolyethers Fomblin HC/04 or Fomblin HC-OH, silicone, carbomer and water. Measurement of the droplet size and examination of the microscopic images confirmed their physicochemical stability over the observation period of eight weeks. Franz-type diffusion cell experiments revealed no increase in curcumin permeation due to the employed perfluoropolyethers compared to the respective control formulations. The formulations used as control were O/W macroemulsions with or without a Polysorbate 80/Sorbitane monooleate 80 surfactant combination. Likewise, tape stripping studies showed no penetration enhancing effect of the employed perfluoropolyethers which is desirable as both perfluoropolyethers are commonly applied components in human personal-care products.

Simultaneous determination of active component and vehicle penetration from F-DPPC liposomes into porcine skin layers.

Liposomes have been used as innovative delivery vehicles on skin for a number of years due to their positive influence on skin penetration. However, until now it is not entirely clear how and by which mechanism enhancement is achieved. In the present study, the skin permeation of a model substance incorporated into liposomes and a control formulation was compared to study the influence of the vehicle in Franz-type diffusion cell experiments. Furthermore, the penetration depths of both components were studied by simultaneous determination of the active substance and the vehicle component during tape stripping studies and horizontal sectioning. For these purposes we prepared liposomes with 1-palmitoyl-2-(16-fluoropalmitoyl)-sn-glycero-3-phosphocholine (F-DPPC), the monofluorinated analogue of dipalmitoylphosphaditylcholine (DPPC) loaded with sodium fluorescein (SoFl). A sodium-fluorescein solution was used as control formulation. While the semi-solid F-DPPC liposomes and the SoFl-solution performed equally well with similar permeation profiles during skin diffusion experiments, superior penetrated amounts of SoFl into the stratum corneum (SC) from F-DPPC liposomes compared to the SoFl-solution were observed possibly due to a "push" exerted by the vehicle F-DPPC. We also showed that SoFl penetrated through SC into the viable epidermis.

Assessment of Raman spectroscopy as a fast and non-invasive method for total stratum corneum thickness determination of pig skin.

Determination of total stratum corneum (SC) thickness is necessary to construct accurate SC drug concentration depth profiles that are used to evaluate the skin absorption of locally acting active components. Currently, different established methods such as the microscopic or gravimetric approach, estimation via transepidermal water loss or NIR densitometry are used. However, some of them represent time consuming strategies. In the present study, Raman spectroscopy was assessed as a non-invasive and fast method for total SC thickness estimation. All techniques employed in this study yielded comparable results with SC values of 11.15 ± 1.52 µm derived from Raman experiments, 10.22 ± 2.64 µm from NIR densitometry measurements and 10.91 ± 2.03 µm from light microscopy studies suggesting Raman spectroscopy as an appropriate and rapid method for total SC thickness determination. As a further objective of the study, the storage conditions of the skin samples during Raman measurements and the impact of keeping the skin on the cartilage during NIR densitometry measurements were investigated. Skin samples can be stored dry during Raman measurements, if immediate measurement is not feasible. Furthermore, skin samples for NIR densitometry studies should be kept on the cartilage during the stripping procedure to avoid SC thickness underestimation.

Investigation of microemulsion microstructure and its impact on skin delivery of flufenamic acid.

Microemulsions are well known penetration enhancing delivery systems. Several properties are described that influence the transdermal delivery of active components. Therefore, this study aimed to characterize fluorosurfactant-based microemulsions and to assess the impact of formulation variables on the transdermal delivery of incorporated flufenamic acid. The microemulsion systems prepared in this study consisted of bistilled water, oleic acid, isopropanol as co-solvent, flufenamic acid as active ingredient and either Hexafor(TM)670 (Hex) or Chemguard S-550-100 (Sin) as fluorosurfactant. Characterization was performed by a combination of techniques including electrical conductivity measurements, small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) self-diffusion experiments. In vitro skin permeation experiments were performed with each prepared microemulsion using Franz type diffusion cells to correlate their present microstructure with their drug delivery to skin. Electrical conductivity increased with added water content. Consequently, the absence of a conductivity maximum as well as the NMR and SAXS data rather suggest O/W type microemulsions with spherical or rod-like microstructures. Skin permeation data revealed enhanced diffusion for Hex- and Sin-microemulsions if the shape of the structures was rather elongated than spherical implying that the shape of droplets had an essential impact on the skin permeation of flufenamic acid.

Semi-solid fluorinated-DPPC liposomes: Morphological, rheological and thermic properties as well as examination of the influence of a model drug on their skin permeation.

The goal of this study was to investigate the influence of an incorporated model drug on the skin permeation of the vehicle itself as it may affect the microstructure and properties of the applied formulation via molecular interactions. For this purpose, we performed skin permeation studies using liposomes prepared with F-DPPC, a monofluorinated analog of dipalmitoylphosphatidylcholine (DPPC), with and without sodium fluorescein (SoFl) serving as model drug. Interestingly, the liposome preparation with F-DPPC yielded semi-solid opalescent systems. Hence, a thorough characterization was accomplished beforehand by electron microscopy imaging, rheological and thermoanalytical experiments. Freeze-fracture electron microscopy images confirmed the existence of globular shaped vesicles in the F-DPPC preparations and oscillatory rheological measurements proved the viscoelastic properties of F-DPPC and F-DPPC+SoFl liposomes in contrast to the viscous characteristics of DPPC liposomes. Thermoanalytical measurements revealed an increased phase transition temperature Tm of about 50 °C for F-DPPC and F-DPPC+SoFl liposomes compared to pure DPPC liposomes with a Tm of about 43° C. The similar Tm of F-DPPC+SoFl and F-DPPC liposomes as well as the similar skin permeation of the vehicle compound F-DPPC compared to its drug-free counterpart suggest an incorporation of sodium fluorescein into the aqueous core of F-DPPC liposomes.