title: The use of SLN and NLC as topical particulate carriers for imidazole antifungal agents.
abstract: Two different imidazole antifungal agents have been used as model drugs to be incorporated into solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), once they are very well established as anti-mycotics for the treatment of topical fungal infections. Because of the high mucoadhesive properties and the strong in situ gelling properties of polyacrylic acid polymers, hydrogels prepared with those macromolecules might be a promising vehicle for imidazole-loaded lipid nanoparticles, such as the above-mentioned SLN and NLC. Thus, in this study Carbopol 934 has been selected for the preparation of semi-solid formulations based on SLN and NLC. Formulations have been stored at three different temperatures before and after particle incorporation into polyacrylate hydrogels. The particle size and the chemical stability of incorporated model drugs have been monitored by HPLC analysis for two years. On the day of production 91.7% and 98.7% of clotrimazole, but only 62.1% and 70.3% of ketoconazole have been recovered from SLN and NLC, respectively. More than 95% of clotrimazole but less than 30% of ketoconazole were detected in the developed formulations after a shelf life of two years. Those values showed to be higher than those obtained with reference emulsions of similar composition and droplet sizes. By rheological measurements a pseudoplastic behaviour with thixotropic properties has been characterized for all semi-solid systems.
authors.affiliation: Department of Pharmaceutics, Biopharmaceutics and Biotechnology, Free University of Berlin, Germany.
authors.forename: E B
authors.initials: EB
authors.lastname: Souto
authors.forename: R H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003022:Clotrimazole / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004356:Drug Storage; D004563:Electrochemistry; D020100:Hydrogels; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry*; D007654:Ketoconazole / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D049329:Nanostructures; D010316:Particle Size; D012212:Rheology; D013696:Temperature; D014783:Viscosity
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D020100:Hydrogels; D007093:Imidazoles; D008055:Lipids; D003022:Clotrimazole; D007654:Ketoconazole