María José García-Celma

Surfactants for microemulsions

Research effort in past years has focused on the development of microemulsions with specific properties, namely, high solubilizing power and temperature insensitivity. Phase behavior studies have provided the foundations for this development. On the basis of mass balance analysis and the geometry of three-phase tie triangles, the composition of the surfactant films separating micro-water and oil domains in bicontinuous type microemulsions has been determined. This information allows a better comparison of the solubilizing power of surfactants. In addition, decisive progress has been made in the development of surfactant systems for the preparation of biocompatible microemulsions.

Solubilization of antifungal drugs in water/POE(20) sorbitan monooleate/ oil systems

Abstract Solubilization of antifungal drugs (clotrimazole, ciclopirox olamine and econazole nitrate) by means of nonionic surfactant systems has been investigated. The solubility of these antifungal drugs ranged from practically insoluble to slightly soluble in water as well as in oils such as isopropyl myristate (IM) and isopropyi palmitate (IP). Ternary water/POE(20) sorbitan monooleate/oil compositions were used to study drug Solubilization in a concentration of 1% w/w. Rheological properties have been studied to determine the suitability of selected compositions as topical formulations. The results obtained show that it is possible to solubilize 1% w/w of antifungal agent in suitable topical formulations with a water content higher than 50% w/w.

Formation of Pegylated Polyurethane and Lysine-Coated Polyurea Nanoparticles Obtained from O/W Nano-emulsions

The present work describes the formation of Pegylated polyurethane and Lysine-coated polyurea nanoparticles obtained from O/W nano-emulsions via an interfacial polycondensation process in the aqueous solution/polysorbate 80/diisocyanate/medium chain triglyceride systems. The initial nano-emulsions were prepared using the phase inversion composition (PIC) method. Dynamic light scattering studies revealed the changes in the particle size occurring during the process of nanoparticle formation. Well-defined polymeric nanoparticles with a small particle diameter (below 80 nm) and low polydispersity index were obtained using a highly hydrophilic component (polyethylene glycol or lysine) and an aliphatic diisocyante monomer. FT-IR and AFM studies showed that the polymeric matrix of nanoparticles was built by copolymers derived from reaction between the diisocyanate and the hydroxyl groups of both nonionic surfactant and the highly hydrophilic component. Pegylated-polyurethane and lysine-coated polyurea nanoparticles designed in this study are promising tools for future applications in biomedical sciences.

Transdermal delivery of forskolin from emulsions differing in droplet size

The skin permeation of forskolin, a diterpene isolated from Coleus forsholii, was studied using oil in water (O/W) emulsions as delivery formulations and also an oil solution for comparative purposes. Two forskolin-loaded emulsions of water/Brij 72:Symperonic A7/Miglyol 812:Isohexadecane, at 0.075 wt% forskolin concentration were prepared with the same composition and only differing in droplet size (0.38 μm and 10 μm). The emulsions showed high kinetic stability at 25 °C. In vitro study of forskolin penetration through human skin was carried out using the MicroettePlus(®) system. The concentration of the active in the receptor solution (i.e. ethanol/phosphate buffer 40/60, v/v) was analyzed by high performance liquid chromatography with UV detection. The obtained results showed that forskolin permeation from the emulsions and the oil solution, through human skin, was very high (up to 72.10%), and no effect of droplet size was observed.

Drug delivery properties of macroporous polystyrene solid foams

PURPOSE Polymeric porous foams have been evaluated as possible new pharmaceutical dosage forms. METHODS These materials were obtained by polymerization in the continuous phase of highly concentrated emulsions prepared by the phase inversion temperature method. Their porosity, specific surface and surface topography were characterized, and the incorporation and release of active principles was studied using ketoprofen as model lipophilic molecule. RESULTS Solid foams with very high pore volume, mainly inside macropores, were obtained by this method. The pore morphology of the materials was characterized, and very rough topography was observed, which contributed to their nearly superhydrophobic properties. These solid foams could be used as delivery systems for active principles with pharmaceutical interest, and in the present work ketoprofen was used as a model lipophilic molecule. CONCLUSIONS Drug incorporation and release was studied from solid foam disks, using different concentrations of the loading solutions, achieving a delayed release with short lag-time.

NLCs as a potential carrier system for transdermal delivery of forskolin

Nanostructured lipid carriers (NLC) composed of the substances generally recognized as safe (GRAS) were obtained by using a hot high-pressure homogenization technique (HPH). The influence of the number of homogenization cycles and concentration of a decyl glucoside surfactant on the NLC properties were studied. The systems stability was assessed by macroscopic observation, light backscattering and zeta potential measurements. NLC particle size was measured using dynamic light scattering (DLS). The kinetically stable formulations were loaded with forskolin and selected for in vitro drug permeation study using the Franz cell method. Concentration of forskolin in the receptor solution (i.e. ethanol/PBS mixture) was analyzed with high performance liquid chromatography (HPLC) with UV detection. The obtained results have shown that NLC formulations could be used as effective carriers for forskolin permeation through the skin.

Nano-emulsions as vehicles for topical delivery of forskolin

Two O/W forskolin-loaded nano-emulsions (0.075% wt.) based on medium chain triglycerides (MCT) and stabilized by a nonionic surfactant (Polysorbate 80 or Polysorbate 40) were studied as forskolin delivery systems. The nano-emulsions were prepared by the PIC method. The mean droplet size of the nano-emulsions with Polysorbate 80 and Polysorbate 40 with oil/surfactant (O/S) ratios of 20/80 and 80% water concentration, measured by Dynamic Light Scattering (DLS), was of 118 nm and 111 nm, respectively. Stability of the formulations, as assessed by light backscattering for 24 h, showed that both nano-emulsions were stable at 25°C. Studies of forskolin in vitro skin permeation from the nano-emulsions and from a triglyceride solution were carried out at 32°C, using Franz-type diffusion cells. A mixture of PBS/ethanol (60/40 v/v) was used as a receptor solution. The highest flux and permeability coefficient was obtained for the system stabilized with Polysorbate 80 (6.91±0.75 µg · cm-2·h-1 and 9.21 · 10-3±1.00 · 10-3 cm · h-1, respectively) but no significant differences were observed with the flux and permeability coefficient value of forskolin dissolved in oil. The obtained results showed that the nano-emulsions developed in this study could be used as effective carriers for topical administration of forskolin.