Rheological and in vitro release behaviour of clotrimazole-containing aqueous SLN dispersions and commercial creams

Clotrimazole is a wide spectrum local imidazolic antifungal agent used in several dermatological creams, having e.g. 1% (m/m) such as Canesten® and Fungizid-ratiopharm® cream. In the present work, a new system based on solid lipid nanoparticles (SLN^TM) containing the identical concentration of drug has been developed. A comparative study between the rheological properties of the referred creams and the developed aqueous SLN dispersions was carried out. The influence of incorporation of SLN in a standard hydrophilic cream on its flow curves was also assessed. In addition, the release of clotrimazole from the two commercial creams, as well as from aqueous SLN dispersions was studied. Concerning the rheological investigations, all tested commercial creams revealed very low shear rates and no yield points. Lipid nanoparticles having a mean diameter of approx. 200 nm have been incorporated into a hydrophilic cream, in a concentration of 20%, 30% or 40% (m/m). The hydrophilic cream containing 20% of SLN showed a dilatant-like character; however, increasing the percentage of incorporated lipid nanoparticles to 30% and 40% the formulation changed to a more pseudoplastic character, showing yield values of 28 Pa and 39 Pa, respectively. For in vitro release studies, Franz diffusion cells with a cellulose acetate membrane were used to measure the release of clotrimazole from two different commercial formulations in comparison to the aqueous SLN dispersion. After 6 h the amount of drug released was higher than 48% when delivered from both investigated commercial formulations and not higher than 25% when delivered from the aqueous SLN dispersion. The percentage of drug released determined after 24 h was more than 50% for Canesten® cream and Fungizid-ratiopharm® cream and not higher than 30% for the developed SLN formulation showing its prolonged release character.