Topical drug delivery by Sepineo P600 emulgel: Relationship between rheology, physical stability, and formulation performance.

ABSTRACT

The objective of this present work was to develop and optimize oil-in-water (O/W) emulsion-based gels, namely emulgels that allow maximum topical drug delivery while having desired microstructure and acceptable physical stability. Emulgels containing 2.0 wt% lidocaine were prepared using various concentrations (0.75-5.0 wt%) of Sepineo P600. Their droplet size distribution, physical stability, rheological behaviors, in vitro drug release, and skin permeation profiles were evaluated. Results show that the concentration of Sepineo P600 significantly influenced the microstructure, rheology, and physical stability of the emulgel formulations. The physico-chemical properties also reveals that at least 1.0 wt% Sepineo P600 was needed to produce stable emulgel formulations. All formulations exhibited non-Newtonian shear-thinning properties which are desirable for topical applications. Both the release and permeation rates decreased with increasing viscosity and rigidity of the formulation. The lower the complex modulus of the emulgels, the higher the steady-state flux of the drug through the skin. Adding Sepineo P600 to emulgel systems resulted in increased rheological properties, which in turn slowed the diffusion of the drug for in vitro release. Although as expected skin permeation was rate limiting since in vitro release was 3 to 4 log-fold faster than skin flux. However, an interesting finding was that the derived skin/vehicle partition coefficient suggested the ionic interaction between lidocaine and Sepineo polymer reducing the free drug, i.e., thermodynamic activity and hence the flux with increasing Sepineo P600 concentration. Overall, this study has provided us with valuable insights into understanding the relationship between the microstructure (rheology), physical stability and skin drug delivery properties which will help to design and optimize topical emulgel formulations.