Ambiguity of experimental spin information from states with mixed orbital symmetries.

The spin texture of the unoccupied bands of the surface alloy Bi/Ag(111) is investigated with spin- and angle-resolved inverse photoemission and first-principles calculations. Surprisingly, the measured spin character does not always reflect the calculated spin texture of the bands. With the help of photoemission calculations within the one-step model, however, the discrepancy is traced back to the influence of the orbital symmetry of the respective states in combination with the experimental geometry. In particular, the calculations show that the spin texture of a surface band with mixed orbital symmetries may neither be recovered with s- nor p- nor unpolarized light. In general, spin information from direct or inverse photoemission experiments on electronic states with mixed orbital symmetries at spin-orbit-influenced surfaces has to be taken with a pinch of salt, while it remains reliable for states with pure symmetry.

Sunblocking efficiency of various TiO(2)-loaded solid lipid nanoparticle formulations(1).

In this study, titanium dioxide (TiO(2)) was incorporated into solid lipid nanoparticle (SLN) formulations using both classical and novel preparation methods. The SLNs were investigated by evaluating their stabilities and physicochemical characteristics. UV-protection abilities of formulations were investigated using in vitro Transpore and Sun To See(TM) test methods. Results have been discussed by comparing the classical SLN formulation with the novel SLN, hybrid SLN (H-SLN) and the emulsion formulations. The results showed the superiority of the H-SLN formulations compared with the classical SLN; all SLN formulations were better when compared with the emulsion formulations considering the UV protection. Incorporation of TiO(2) as a sunscreen agent into SLN formulations gives opportunity to produce stable and safe formulations with reduced amount but high UV-protection ability.

Skin moisturizing effect and skin penetration of ascorbyl palmitate entrapped in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) incorporated into hydrogel.

This study was performed as a complimentary to our previous study regarding the chemical stability of ascorbyl palmitate (AP) in solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, in nanoemulsion (NE) incorporated into a hydrogel produced by high pressure homogenization. AP is known as an effective antioxidant that protects tissue integrity similar to vitamin C. Recently, its moisturizing activity in conventional topical formulations was found to be high. The aim of the present study was to investigate the moisturizing potential of AP in SLN and NLC incorporated into hydrogel as colloidal carrier systems. It has been known that SLN and NLC have occlusive effects, but AP incorporation moisturized skin significantly better than placebo in short-term (p < 0.001) and long-term trials (p < 0.01) for both SLN and NLC. In the second part of the study, SLN and NLC were found to sustain the penetration of AP through excised human skin about 1/2 and 2/3 times compared to NE (p < 0.001 and p < 0.01), respectively, due to the solid state of Witepsol E85 in the lipid phase.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate.

The aim of this study was to improve the chemical stability of ascorbyl palmitate (AP) in a colloidal lipid carrier for its topical use. For this purpose, AP-loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, a nanoemulsion (NE) were prepared employing the high pressure homogenization technique and stored at room temperature (RT), 4 degrees C and 40 degrees C. During 3 months, physical stability of these formulations compared to placebo formulations which were prepared by the same production method, was studied including recrystallization behaviour of the lipid with differential scanning calorimetry (DSC), particle size distribution and storage stability with photon correlation spectroscopy (PCS) and laser diffractometry (LD). After evaluating data indicating excellent physical stability, AP-loaded SLN, NLC and NE were incorporated into a hydrogel by the same production method as the next step. Degradation of AP by HPLC and physical stability in the same manner were investigated at the same storage temperatures during 3 months. As a result, AP was found most stable in both the NLC and SLN stored at 4 degrees C (p > 0.05) indicating the importance of storage temperature. Nondegraded AP content in NLC, SLN and NE was found to be 71.1% +/- 1.4, 67.6% +/- 2.9 and 55.2% +/- 0.3 after 3 months, respectively. Highest degradation was observed with NE at all the storage temperatures indicating even importance of the carrier structure.

Solid lipid nanoparticles (SLN) for topical drug delivery: incorporation of the lipophilic drugs N,N-diethyl-m-toluamide and vitamin K.

Solid lipid nanoparticles (SLN) for topical delivery were prepared by high pressure homogenization using solid lipids. The lipophilic agents DEET (N,N-diethyl-m-toluamide) and vitamin K were used as model drugs. These topical agents were incorporated into SLN which were characterized. Differential scanning calorimetry studies were performed in order to detect probable interactions in the SLN dispersions. Physical stability of SLN in aqueous dispersions and the effect of drug incorporation into SLN were investigated by photon correlation spectroscopy and zeta potential measurements. Characterization and short-term stability studies showedthat DEET and vitamin K are good candidates for topical SLN formulations.

Comparative study between the viscoelastic behaviors of different lipid nanoparticle formulations.

Application of drug substances to the skin for systemic absorption or action in a particular layer of the skin is a rather old approach. However, over the last years it has received much more attention, as a consequence of the development of new membrane-moderated and matrix reservoir devices. As new reservoir systems, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been successfully tested for dermal application of different physicochemical substances. The knowledge obtained from rheological investigations of these systems may be highly useful for the characterization of the newly developed topical formulation. In the present study, an oscillation frequency sweep test was used for the evaluation of storage modulus (G'), loss modulus (G''), and complex viscosity (eta*) of twelve different SLN and NLC formulations, over a frequency range from 0 to 10 Hz. The lipidic aqueous dispersions were prepared using three different solid lipids (Softisan138, Compritol888, and stearyl alcohol) as matrix material. Miglyol812, tocopherol, sunflower oil, and long-chain triacylglycerols were the chosen liquid lipids for NLC preparation. The objective of the present work was to investigate the effect of these different liquid lipids on the rheological properties of aqueous dispersions of NLC as model systems. It was found that the liquid oil component of the formulation has a strong influence on the viscoelastic parameters, which are dependent on the particle size, zeta potential, and crystallinity of the lipid particles, as well as on the solid lipid used.

Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations.

Aqueous dispersions of lipid nanoparticles are being investigated as drug delivery systems for different therapeutic purposes. One of their interesting features is the possibility of topical use, for which these systems have to be incorporated into commonly used dermal carriers, such as creams or hydrogels, in order to have a proper semisolid consistency. For the present investigation four different gel-forming agents (xanthan gum, hydroxyethylcellulose 4000, Carbopol943 and chitosan) were selected for hydrogel preparation. Aqueous dispersions of lipid nanoparticles--solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC)--made from tripalmitin were prepared by hot high pressure homogenization and then incorporated into the freshly prepared hydrogels. NLC differ from SLN due to the presence of a liquid lipid (Miglyol812) in the lipid matrix. Lipid nanoparticles were physically characterized before and after their incorporation into hydrogels. By means of rheological investigations it could be demonstrated that physical properties of the dispersed lipid phase have a great impact on the rheological properties of the prepared semisolid formulations. By employing an oscillation frequency sweep test, significant differences in elastic response of SLN and NLC aqueous dispersions could be observed.

Influence of surfactants on the physical stability of solid lipid nanoparticle (SLN) formulations.

The choice of surfactant or surfactant mixtures at suitable concentrations contributes to the stability of solid lipid nanoparticles (SLN). In this study, it was found that 1.5% TegoCare 450 was the most effective stabilizer for the Witepsol E85 SLN dispersion compared to Tween 80, Tyloxapol and Pluronic F68 according to the data obtained from differential scanning calorimetry (DSC), zeta potential (ZP) measurements and particle size analysis.

Development of a controlled release formulation based on SLN and NLC for topical clotrimazole delivery.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are colloidal carrier systems providing controlled release profiles for many substances. Clotrimazole-loaded SLN and NLC were prepared by the hot high pressure homogenization technique in order to evaluate the physical stability of these particles, as well as the entrapment efficiency of this lipophilic drug and its in vitro release profile. The particle size was analyzed by PCS and LD showing that the particles remained in their colloidal state during 3 months of storage at 4, 20 and 40 degrees C. For all tested formulations the entrapment efficiency was higher than 50%. The obtained results also demonstrate the use of these lipid nanoparticles as modified release formulations for lipophilic drugs over a period of 10 h.

Solid lipid nanoparticles for parenteral drug delivery.

This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC) nanoparticles are introduced and structural differences are pointed out. Different production methods including the suitability for large scale production are described. Stability issues and drug incorporation mechanisms into the particles are discussed. In the second part, the biological activity of parenterally applied SLN and biopharmaceutical aspects such as pharmacokinetic profiles as well as toxicity aspects are reviewed.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations.

Solid lipid nanoparticles (SLN) were developed at the beginning of the 1990 s as an alternative carrier system to emulsions, liposomes and polymeric nanoparticles. The paper reviews advantages-also potential limitations-of SLN for the use in topical cosmetic and pharmaceutical formulations. Features discussed include stabilisation of incorporated compounds, controlled release, occlusivity, film formation on skin including in vivo effects on the skin. As a novel type of lipid nanoparticles with solid matrix, the nanostructured lipid carriers (NLC) are presented, the structural specialties described and improvements discussed, for example, increase in loading capacity, physical and chemical long-term stability, triggered release and potentially supersaturated topical formulations. For both SLN and NLC, the technologies to produce the final topical formulation are described, especially the production of highly concentrated lipid nanoparticle dispersions >30-80% lipid content. Production issues also include clinical batch production, large scale production and regulatory aspects (e. g. status of excipients or proof of physical stability).

Nanostructured lipid matrices for improved microencapsulation of drugs.

At the beginning of the nineties solid lipid nanoparticles (SLN) have been introduced as a novel nanoparticulate delivery system produced from solid lipids. Potential problems associated with SLN such as limited drug loading capacity, adjustment of drug release profile and potential drug expulsion during storage are avoided or minimised by the new generation, the nanostructured lipid carriers (NLC). NLC are produced by mixing solid lipids with spatially incompatible lipids leading to special structures of the lipid matrix, i.e. three types of NLC: (I) the imperfect structured type, (II) the structureless type and (III) the multiple type. A special preparation process-applicable to NLC but also SLN-allows the production of highly concentrated particle dispersions (>30-95%). Potential applications as drug delivery system are described.

The development of an improved carrier system for sunscreen formulations based on crystalline lipid nanoparticles.

The aim of this study was the in vitro evaluation of the efficacy of two different carrier systems for the molecular sunscreen benzophenone-3. One carrier system was a conventional o/w emulsion, the other consisted of highly crystalline lipid nanoparticles (CLN). It was observed that CLN act as physical sunscreens themselves and show improved photoprotection compared with a placebo emulsion with the same lipid content. Incorporation of a molecular sunscreen further improves the protection level in a synergistic way. This in vitro study based on the Transpore test by Diffey showed that the amount of molecular sunscreen can be decreased by up to 50% while maintaining the UV protection efficacy. Therefore, the use of CLN as an active carrier for sunscreens is a promising innovation.

The influence of the crystallinity of lipid nanoparticles on their occlusive properties.

The aim of this study was the investigation of the correlation between the degree of crystallinity of solid lipid nanoparticle (SLN) dispersions and their occlusive effects. SLN dispersions with different crystallinity indices of the lipid matrix were produced, physicochemically characterized and their occlusion factor was determined after 6, 24 and 48 h. This study is based on the in vitro occlusion test by de Vringer. It could be shown that the occlusion factor depends strongly on the degree of crystallinity of the lipid matrix, i.e. this effect is proportional. Further, it could be shown that noncrystalline lipid nanoparticles, i.e. supercooled melts have no occlusive properties. Therefore, the desired degree of occlusivity can be achieved by choosing suitable lipids for the matrices of topical SLN formulations.

Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo skin penetration.

The aim of this study was the comparison of two different formulations (solid lipid nanoparticles (SLN) and conventional o/w emulsion) as carrier systems for the molecular sunscreen oxybenzone. The influence of the carrier on the rate of release was studied in vitro with a membrane-free model. The release rate could be decreased by up to 50% with the SLN formulation. Further in vitro measurements with static Franz diffusion cells were performed. In vivo, penetration of oxybenzone into stratum corneum on the forearm was investigated by the tape stripping method. It was shown that the rate of release is strongly dependent upon the formulation and could be decreased by 30-60% in SLN formulations. In all test models, oxybenzone was released and penetrated into human skin more quickly and to a greater extent from the emulsions. The rate of release also depends upon the total concentration of oxybenzone in the formulation. In vitro-in vivo correlations could be made qualitatively.

Solid lipid nanoparticles (SLN)--a novel carrier for UV blockers.

The formulation of safe sunscreen products is of high importance due to their increasing use because of the diminishing ozone layer. Solid lipid nanoparticles (SLN) are introduced as the new generation of carriers for cosmetics, especially for UV blockers for the use on human skin and/or hair and production thereof is described. The crystalline cetylpalmitate SLN particles have the ability of reflecting and scattering UV radiation on their own thus leading to photoprotection without the need for molecular sunscreens. An in vitro assay showed that a placebo cetyl palmitate SLN formulation is twice to three times as potent in absorbing UV radiation as a conventional emulsion. Incorporation of sunscreens into SLN lead to a synergistic photoprotection, i.e. higher than the additive effect of UV scattering caused by the SLN and UV absorption by the sunscreen. The photoprotective effect after incorporation of the molecular sunscreen 2-hydroxy-4-methoxybenzophenone (Eusolex 4360) into the SLN dispersion was observed to be increased threefold compared to a reference emulsion. Further, film formation on the skin was investigated by scanning electron microscopy, showing particle fusion due to water evaporation and formation of a dense film.

Investigations on the occlusive properties of solid lipid nanoparticles (SLN).

Skin hydration can be influenced to a great extent by occlusive compounds. Conventional highly occlusive compounds tend to have an unacceptable appearance. Therefore, the development of innovative occlusive topicals is an essential issue regarding the formulation of cosmetic and pharmaceutical preparations. Solid lipid nanoparticles (SLN) represent a novel carrier system for controlled release of topical cosmetic and pharmaceutical compounds. In addition to their controlled release characteristics, it has been found that SLN have an occlusive effect. The extent of the occlusive effect depends on various factors such as particle size, applied sample volume, lipid concentration, and crystallinity of the lipid matrix. These factors have been investigated in detail by an in vitro test, and the obtained data give insight into their importance.

A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles.

Solid lipid nanoparticles (SLN) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLN possess characteristics of physical UV-blockers on their own, thus offering the possibility of developing a more effective sunscreen system with reduced side-effects. Incorporation of the chemical sunscreen tocopherol acetate into SLN prevents chemical degradation and increases the UV-blocking capacity. Aqueous SLN dispersions were produced and incorporated into gels, followed by particle size examination, stability testing upon storage and thermoanalytical examination. Investigation of the UV-blocking capacity using different in vitro techniques revealed that the SLN dispersions produced in this study are at least twice as effective as their reference emulsions (conventional emulsions with identical lipid content). Placebo SLN even show greater UV-blocking efficacy than emulsions containing tocopherol acetate as the molecular sunscreen. Incorporation of tocopherol acetate into SLN leads to an overadditive UV-blocking effect. Furthermore, film formation of SLN on the skin and occlusivity were examined. The obtained data show that incorporation of tocopherol acetate into SLN leads to an improved sunscreen and skin care formulation.

An investigation into the use of stepwise isothermal high sensitivity DSC as a means of detecting drug-excipient incompatibility.

The use of stepwise isothermal high sensitivity differential scanning calorimetry (HSDSC) as a novel means of detecting excipient incompatibility is described using aspirin mixes with magnesium stearate and stearic acid as model systems. Aspirin, magnesium stearate and stearic acid alone and as mixes were studied in scanning mode using conventional DSC and were then subjected to a stepwise heating programme using HSDSC, whereby the samples were heated to temperatures between 45 and 70 degrees C and held for 1 h, during which the heat flow to or from the sample was measured. The data indicated that while no thermal events were detected for the individual components or mixes with stearic acid other than melting of stearic acid, 50% w/w mixes of magnesium stearate showed a marked endothermic response at temperatures above 55 degrees C. The data were fitted to an adaptation of an existing kinetic model for the degradation process and a reasonable correlation found. Mixes of the drug with the two excipients were then studied at 60 degrees C over 6 h at concentrations between 1 and 50% w/w. Incompatibilities with magnesium stearate concentrations as low as 1% w/w could be detected using this approach. Compacts of magnesium stearate and aspirin were also studied, with considerably more pronounced thermal events taking place compared to the powder mixes. It is concluded from these studies that while the study has highlighted certain limitations of the approach, stepwise isothermal DSC represents a potentially highly useful means of detecting excipient incompatibilities.

Influence of high pressure homogenisation equipment on nanodispersions characteristics.

In this study a comparison of the influence of the homogenising equipment supplied by different manufacturers on the quality of the lipid nanodispersions is given. An Avestin EmulsiFlex-B3 (B3) and APV Micron Lab 40 (LAB 40) were used for high pressure homogenisation. Particle size and particle size distribution were chosen as quality parameters. The influence of different process parameters was evaluated. The two homogenisers were compared in their quality of nanoparticles-production by hot and cold homogenisation technique and in processing nanoemulsions. Working with the B3 appeared as useful for preformulation studies and processing of expensive or rare drugs and excipients. This first scaling up within laboratory scale is evaluated and the problems and remarkable aspects working with the B3 are pointed out.