In vitro percutaneous absorption of all-trans retinoic acid applied in free form or encapsulated in stratum corneum lipid liposomes.

The objective of this study was to design an all-trans retinoic acid (RA) topical release system that modifies drug diffusion parameters in the vehicle and the skin in order to reduce systemic absorption and the side-effects associated with topical application of the drug to skin. Three cases of application of hydrogels containing RA either in free form or encapsulated in stratum corneum lipid liposomes (SCLLs) have been considered. For this purpose, we have evaluated the RA in formulations with combinations of Carbopol Ultrez 10 (U10) and hyaluronic acid (HA) for percutaneous absorption. In vitro permeability experiments with [3H]-t-RA were carried out using a Franz-type diffusion cell in abdominal rat skin samples. Accumulation of the drug in the surface and skin layers was evaluated by both the tape stripping method and a dissection technique, and subsequently, all the radiolabelled samples were analyzed by liquid scintillation counting. The results show that RA encapsulation not only prolongs drug release but also promotes drug retention by the viable skin. At the same time, interaction between RA and HA has an obstructive effect on diffusion, which contributes to the formation of a reservoir of the latter.

Rheological characterization of hydroalcoholic gels--15% ethanol--of Carbopol Ultrez 10.

The rheological behaviour of Carbopol Ultrez 10 ethanolic (15%) gels was studied as a function of two main variables: pH (4.0-7.0) and the polymer concentration (0.1-0.5%). Flow curves of all hydroalcoholic gels were adjusted to the Ostwald model. Sigmoidal dose response functions were obtained to describe the pH dependence of consistency index of the systems. The concentration dependence of flow indexes was best adjusted to one-phase exponential decay functions. Finally, by substituting in the power law expression, an empirical model is given to estimate viscosities of gels for any value of pH and polymer concentration in the ranges evaluated. As a result, the influence of the variables on polymer network is meaningfully assessed by means of the obtained empirical parameters: bottom value (Ymax), pH value required for a 50% polymer network development (pH50), and asymptotic flow index value for the fully structured gels (n(min)).

Viscosity and temperature relationship in ethanol/water mixtures gelified with Carbopol Ultrez 10.

The rheological characterization of Carbopol Ultrez 10 ethanolic (15%) gels is complemented by studying flow behavior as a function of temperature (20-50 degrees C) at different pH (4.0-7.0) and polymer concentrations (0.1-0.5%). Flow curves were adjusted to the Ostwald model, showing a fall in viscosity, together with an enhancement in flow index with increasing temperature. Calculated flow activation energies at constant shear rate (Egamma) were found to be related to the final pH of hydroalcoholic gels. Nevertheless, at the polymer concentration range evaluated, no significant correlations were obtained between activation energy and concentration. In general, the Carbopol Ultrez 10 gels exhibit little viscosity change under the temperature variations of normal use and storage, which minimizes possible unacceptable changes in the product's characteristics.