Structural investigations on nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers by cryo-field emission scanning electron microscopy and Raman spectroscopy

Recently, colloidal dispersions based on solid lipids (solid lipid nanoparticles, SLN) and mixtures of solid and liquid lipids (nanostructured lipid carriers, NLC) were described as innovative carrier systems. A spherical particle shape is the basis of features such as a high loading capacity and controlled drug release characteristics due to smaller lipid-water interfaces and longer diffusion pathways when compared to thin platelets. The structures of SLN and the influence of oil load (NLC) on particle properties were investigated by photon correlation spectroscopy (PCS), laser diffractometry (LD), cryo-field emission scanning electron microscopy (cryo-FESEM), Raman spectroscopy and infrared spectroscopy (IR), and compared to a conventional nanoemulsion. PCS and LD data show similar size and size distribution for SLN and NLC (approximately 210 nm, polydispersity index approximately 0.15) and suggested a long term physical stability for the dispersions which had been stored for up to 12 months at different temperatures. Using cryo-FESEM droplets (for the nanoemulsion) and almost spherical particles for SLN and NLC were observed. Raman spectroscopy resulted in spectra for NLC that are weighted to the SLN spectra, suggesting an undisturbed crystal structure. Infrared spectra of the NLC are predominantly SLN in nature. Importantly the SLN bands are unshifted in the NLC spectrum indicating that the crystalline structure is unaffected by the presence of the oil.     

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.     

Preparation and characteristics of monostearin nanostructured lipid carriers

Nanostuctured lipid carriers (NLC) consisted of solid lipid and liquid lipid are a new type of lipid nanoparticles, which offer the advantage of improved drug loading capacity and release properties. In this study, solvent diffusion method was employed to produce NLC. Monostearin (MS) and caprylic/capric triglycerides (CT) were chosen as the solid lipid and liquid lipid. Clobetasol propionate used as a model drug was incorporated into the NLC. The influences of preparation temperature and CT content on physicochemical properties of the NLC were characterized. As a result, monostearin solid lipid nanoparticles (without CT content, SLN) obtained at higher temperature (70 degrees C) exhibited slightly higher drug loading capacity than that of 0 degrees C (P < 0.05). In contrast, the production temperature made little effect on NLC drug loading capacity (P > 0.05). The improved drug loading capacity was observed for NLC and it enhanced with increasing the CT content in NLC. The results were explained by differential scanning calorimetry (DSC) measurement for NLC. The incorporation of CT to NLC led to crystal order disturbance and thus left more space to accommodate drug molecules. NLC displayed a good ability to reduce the drug expulsion in storage compared to SLN. The in vitro release behaviors of NLC were dependent on the production temperature and CT content. NLC obtained at 70 degrees C exhibited biphasic drug release pattern with burst release at the initial 8h and prolonged release afterwards, whereas NLC obtained at 0 degrees C showed basically sustained drug release throughout the release time. The drug release rates were increased with increasing the CT content. These results indicated that the NLC produced by solvent diffusion method could potentially be exploited as a carrier with improved drug loading capacity and controlled drug release.     

Lipid nanoparticles as carrier for octyl-methoxycinnamate: in vitro percutaneous absorption and photostability studies

The aim of the present study was the evaluation of lipid nanoparticles (solid lipid nanoparticles, SLN, and nanostructured lipid carriers, NLC) as potential carriers for octyl-methoxycinnamate (OMC). The release pattern of OMC from SLN and NLC was evaluated in vitro, determining its percutaneous absorption through excised human skin. Additional in vitro studies were performed in order to evaluate, after UVA radiation treatment, the spectral stability of OMC-loaded lipid nanoparticles. From the obtained results, ultrasonication method yielded both SLN and NLC in the nanometer range with a high active loading and a particle shape close to spherical. Differential scanning calorimetry data pointed out the key role of the inner oil phase of NLC in stabilizing the particle architecture and in increasing the solubility of OMC as compared with SLN. In vitro results showed that OMC, when incorporated in viscosized NLC dispersions (OMC-NLC), exhibited a lower flux with respect to viscosized SLN dispersions (OMC-SLN) and two reference formulations: a microemulsion (OMC-ME) and a hydroalcoholic gel (OMC-GEL). Photostability studies revealed that viscosized NLC dispersions were the most efficient at preserving OMC from ultraviolet-mediated photodegradation.     

Development of an itraconazole-loaded nanostructured lipid carrier (NLC) formulation for pulmonary application

Itraconazole-loaded NLC for pulmonary application were developed. In Precirol ATO 5 and oleic acid Itraconazole had the highest solubility. The solid lipid and the oil were mixable in a ratio 9:1 possessing a melting point above body temperature. 0.4% Itraconazole was dissolved in this lipid blend. Eumulgin SLM 20 was the stabilizer with the highest affinity to the lipid blend used as particle matrix. 2.5% Eumulgin SLM 20 was sufficient to obtain NLC with a narrow particle size distribution and sufficient stability. The tonicity of the formulation was adjusted with glycerol. Sterility was obtained by autoclaving. Neither the addition of glycerol nor autoclaving had an influence on the particle size and the zeta potential of Itraconazole-loaded NLC. SEM images showed spherical particles confirming the particle size measured by light scattering techniques. An entrapment efficiency of 98.78% was achieved. Burst release of Itraconazole from the developed carrier system was found. Itraconazole-loaded NLC possessed good storage stability. Nebulizing Itraconazole-loaded NLC with a jet stream and an ultrasonic nebulizer had no influence on the particle size and the entrapment efficiency of Itraconazole in the particle matrix, being a precondition for pulmonary application.     

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.     

Semisolid SLN dispersions for topical application: influence of formulation and production parameters on viscoelastic properties.

Aqueous solid lipid nanoparticle (SLN) dispersions with a high lipid content up to 35% and viscous to semisolid consistency were produced by a high pressure homogenization process. Despite their high lipid content and viscosity these dispersions preserved their colloidal size range. The SLN dispersions were compared to nanoemulsions and microparticle dispersions with regard to particle size, viscoelastic properties and formation of a semisolid gel structure. Viscoelastic measurements including oscillation stress sweep tests and oscillation frequency sweep tests demonstrated that the existence of a solid particle matrix with a particle size in the nanometer range is a prerequisite to form a semisolid dispersion having the appropriate consistency for topical application. Striking differences were observed between solid lipid micro- and nanodispersions of the same composition. Particle size reduction resulted in an 80-fold increase of the elastic modulus. Particle size distribution, the physical state of the dispersed lipid phase and the emulsifier concentration have been identified as further key factors for the viscoelastic properties and gel structure of the lipid nanodispersions. By conducting oscillation measurements it was possible to relate the stability of lipid dispersions to specific rheological parameters therefore providing a sensitive tool in stability assessment. Changing the production process from a 40 ml batch to a 2 l batch turned out to have an influence on the colloidal structures of semisolid SLN dispersions. Consistency increased but particle size and ratio of elastic to viscous properties stayed in the same range.     

Potential Use of Nanostructured Lipid Carriers for Topical Delivery of Flurbiprofen

The potential use of nanostructured lipid carriers (NLC) composed of a fatty acid [stearic acid (SA)] or a triglyceride (glyceryl behenate) as solid lipids, and a mixture of medium chain triglycerides and castor oil as liquid lipids, for skin administration of flurbiprofen (FB), has been explored. Two different optimized NLC formulations (FB-SANLC based on SA vs. FB-C888NLC based on glyceryl behenate), with respect to the morphometrical properties (particle size and polydispersity index) and the entrapment efficiency, were used in this study. The ex vivo permeation profiles of FB-C888NLC, FB-SANLC and conventional FB solution were evaluated using human skin. An improved FB permeation was observed when the drug was delivered by skin application of FB-C888NLC, attributed to the particle size and matrix crystallinity. The differential scanning calorimetry and X-ray diffraction studies suggested major polymorphic transitions in the lipid matrix of FB-C888NLC. A good correlation between polymorphic transitions and increased drug permeation was observed. However, both NLC dispersions showed a penetration-enhancing ratio (ER) higher than conventional FB solution. The in vitro and in vivo irritancy and local tolerability were assessed by running, respectively, the SKINTEX? and Draize test. Both FB-C888NLC and FB-SANLC were classified as nonirritant.     

Preparation and characterization of n-dodecyl-ferulate-loaded solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) containing a novel potential sunscreen n-dodecyl-ferulate (ester of ferulic acid) were developed. The preparation and stability parameters of n-dodecyl-ferulate-loaded SLN have been investigated concerning particle size, surface electrical charge (zeta potential) and matrix crystallinity. The chemical stability of n-dodecyl-ferulate at high temperatures was also assessed by thermal gravimetry analysis. For the selection of the appropriated lipid matrix, chemically different lipids were melted with 4% (m/m) of active and lipid nanoparticles were prepared by the so-called high pressure homogenization technique. n-Dodecyl-ferulate-loaded SLN prepared with cetyl palmitate showed the lowest mean particle size and polydispersity index, as well as the highest physical stability during storage time of 21 days at 4, 20 and 40 degrees C. These colloidal dispersions containing the sunscreen also exhibited the common melting behaviour of aqueous SLN dispersions.     

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.     

SLN and NLC for topical delivery of ketoconazole

The clinical use of ketoconazole has been related to some adverse effects in healthy adults, specially local reactions, such as severe irritation, pruritus and stinging. The purpose of the present work is the assessment of ketoconazole stability in aqueous SLN and NLC dispersions, as well as the physicochemical stability of these lipid nanoparticles, which might be useful for targeting this drug into topical route, minimizing the adverse side effects and providing a controlled release. Lipid particles were prepared using Compritol 888 ATO as solid lipid. The natural antioxidant alpha-tocopherol was selected as liquid lipid compound for the preparation of NLC. Ketoconazole loading capacity was identical for both SLN and NLC systems (5% of particle mass). SLN were physically stable as suspensions during 3 months of storage, but the SLN matrix was not able to protect the chemically labile ketoconazole against degradation under light exposure. In contrast, the NLC were able to stabilize the drug, but the aqueous NLC dispersion showed size increase during storage. Potential topical formulations are light-protected packaged SLN or NLC physically stabilized in a gel formulation.     

Characterization of physico-chemical properties and pharmaceutical performance of sucrose co-freeze-dried solid nanoparticulate powders of the anti-HIV agent loviride prepared by media milling

Enhancement of the chemical stability of ascorbyl palmitate (AP) after incorporation into nanostructured lipid carriers (NLC) has been reported. However, the formulation parameters of AP-loaded NLC have not been completely investigated. Moreover, the long-term chemical stability of AP in any colloidal systems has not been yet achieved. Therefore, in this study the formulation parameters affecting the stability of AP after incorporation into NLC were evaluated including types of lipids, types of surfactants, storage conditions, i.e. temperature and nitrogen gas flushing, the effects of drug loading as well as types of antioxidants. After storage for 90 days, the mean particle size analyzed by photon correlation spectroscopy (PCS) was lower than 350 nm. The zeta potential measured by the Zetasizer IV was higher than −30 mV in all developed AP-loaded NLC formulations which varied according to the types of lipid and surfactant. Concerning the chemical stability of AP, it was found that AP-loaded NLC prepared and stored in non-degassing conditions, a higher percentage of AP loading in NLC, lower storage temperature (4 °C), addition of antioxidants as well as selection of suitable surfactants and solid lipids improved the chemical stability of AP. Moreover, an improvement of long-term chemical stability of AP was achieved by addition of antioxidants with nitrogen gas flushing as compared to those without antioxidant. The percentage of drug remaining at both 4 °C and room temperature (25 °C) was higher than 85% during 90 days of storage.     

Polymorphic behaviour of Compritol888 ATO as bulk lipid and as SLN and NLC

CompritolR888 ATO (glycerol behenate) is widely used as a pharmaceutical excipient in the field of solid dosage forms due to its lubricating properties. It is an amphiphilic material with a high melting point (approximately 70 degrees C) and, therefore, it can also be used to prepare aqueous colloidal dispersions. The aim of this paper is to study the suitability of CompritolR888 ATO for the production of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the entrapment of a lipophilic model drug. This study assesses the crystalline structure of the bulk lipid, as well as the changes that occur in its crystal lattice with the addition of 'impurities', such as oil (alpha-tocopherol) and drug (ketoconazole), using DSC and X-ray diffraction analysis before and after thermal stress. Aqueous SLN and NLC dispersions were produced using an appropriate surfactant/co-surfactant system and their physicochemical stability was assessed by PCS, LD, DSC and by WAXS. It was found that the crystalline lattice of CompritolR888 ATO is composed of very small amounts of the unstable alpha polymorphic form characteristic of triacylglycerols, which disappears after thermal stress of bulk lipid. Mixing oils and drug molecules which are soluble in this lipid decreased its lattice organization and, thus, was revealed to be suitable for production of lipid nanoparticles containing ketoconazole. However, particle growth could not be avoided during shelf life.     

Characterization of indomethacin-loaded lipid nanoparticles by differential scanning calorimetry

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are interesting nanoparticulate delivery systems produced from solid lipids. Both carrier types are submicron size particles but they can be distinguished by their inner structure. In the present paper, indomethacin (IND)-loaded SLN and NLC were prepared and the organization and distribution of the different ingredients originating each type of nanoparticle system were studied by differential scanning calorimetry (DSC) technique. Furthermore, mean particle size and percentage of drug encapsulation were also determined. From the results obtained, NLC lipid organization guaranteed an increased indomethacin encapsulation in comparison with SLN. DSC static and dynamic measurements performed on SLN and NLC showed that oil nanocompartments incorporated into NLC solid matrix drastically influenced drug distribution inside the nanoparticle system. Controlled release from NLC system could be explained considering both drug partition between oil nanocompartments and solid lipid and a successive partition between solid lipid and water.     

Topical formulation of retinyl retinoate employing nanostructured lipid carriers

Topical formulation of retinyl retinoate (RR) was developed with nanostructured lipid carriers (NLCs), composed of Compritol or Precirol as a solid lipid, canola oil as an oil, and Tween 80 as a surfactant. Hot high pressure homogenization method was efficiently employed to yield a homogenous nanodispersion in the size range of 230?C300?nm with PDI values of <0.2, regardless of lipid selection. Precirol-based NLC (P-NLC) showed higher drug entrapment than that of Compritol-based NLC (C-NLC): RR encapsulation efficiency (%) of P- and C-NLC was 97.8 and 93.8 in average, respectively; drug loading (mg RR/g lipid) was 89.6 and 83.3 in average, respectively. Processing condition at relatively low temperature of 60?°C was a key factor for maintaining RR stability. Drug release of P-NLC was greater than that of C-NLC, even though both NLCs revealed controlled release pattern. Therefore, P-NLC system was considered as a suitable vehicle for topical drug delivery, especially for heat-labile ingredient like RR.     

SLN and NLC for topical delivery of ketoconazole

The clinical use of ketoconazole has been related to some adverse effects in healthy adults, specially local reactions, such as severe irritation, pruritus and stinging. The purpose of the present work is the assessment of ketoconazole stability in aqueous SLN and NLC dispersions, as well as the physicochemical stability of these lipid nanoparticles, which might be useful for targeting this drug into topical route, minimizing the adverse side effects and providing a controlled release. Lipid particles were prepared using Compritol®888 ATO as solid lipid. The natural antioxidant α-tocopherol was selected as liquid lipid compound for the preparation of NLC. Ketoconazole loading capacity was identical for both SLN and NLC systems (5% of particle mass). SLN were physically stable as suspensions during 3 months of storage, but the SLN matrix was not able to protect the chemically labile ketoconazole against degradation under light exposure. In contrast, the NLC were able to stabilize the drug, but the aqueous NLC dispersion showed size increase during storage. Potential topical formulations are light-protected packaged SLN or NLC physically stabilized in a gel formulation.     

Stability of total nutrient admixtures using various intravenous fat emulsions

The stability of four lipid emulsions with amino acids and dextrose in total nutrient admixtures (TNAs) was studied. The admixtures were divided into three groups. In group 1, 24 admixtures representing 20 different combinations of Liposyn II (safflower oil-soybean oil fat emulsion) with various manufacturers' amino acids (FreAmine III, Travasol, Novamine, Nephramine, and RenAmin) were tested. In group 2, 19 TNAs representing 14 combinations containing soybean-oil emulsions (Intralipid, Travamulsion, and Soyacal) and Aminosyn II amino acids were studied. In group 3, 14 TNAs representing 9 combinations containing the above soybean oil emulsions and Aminosyn II with Electrolytes were tested. Both 10% and 20% concentrations of fat emulsion, various amino acid concentrations ranging from 5.4% to 11.4%, and dextrose injections of 10, 20, 40, 50, and 70% were used. The admixtures were compounded in an ethylene vinyl acetate container. The mixing sequence involved transfer of fat emulsion to the empty container, followed by amino acids and dextrose. One of two electrolyte and trace metal profiles was added to each core admixture after compounding. Multivitamins were added just before the 24-hour room-temperature (25 +/- 4 degrees C) storage. Admixtures were tested initially and after one day at room temperature or nine days at 5 degrees C plus one day at room-temperature storage. Measurements of pH, emulsion particle size, osmolality, and zeta potential (electrostatic surface charge of lipid particles) were made after visual inspection of each admixture. In general, the TNAs retained a uniform, milk-like appearance under both storage conditions. The values of pH, zeta potential, particle size, and osmolality remained essentially unchanged throughout the study. Under the conditions of this study, the TNA formulations tested are stable for up to 10 days.     

Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia

In the present work attempts have been made to prepare the nanostructured lipid carrier (NLC) gel, by using minoxidil, which is preferably used in case of Alopecia, i.e. baldness pattern as a effective drug. The nine different formulations of Minoxidil-NLC (NLC1–NLC9) were prepared using solid and liquid lipids with Cholesterol and Soya lecithin in different concentrations by the melt dispersion ultrasonication method. Properties of NLC1–NLC9 such as the particle size and its distribution, the scanning electron microscopy (SEM), the drug entrapment efficiency (EE), and the drug release behavior were investigated. The nanoparticulate dispersion was suitably gelled and characterized with respect to drug content, pH, spreadability, rheology, and in vitro release. Safety of the NLC-based gel was assessed using primary skin irritation studies. The formulated NLC3 was spherical in shape, with average particle size of 280 nm, zeta potential of ?42.40 mV and entrapment efficiency of 86.09%. Differential Scanning Calorimeter (DSC) measurements revealed that imperfect crystallization occurred in the inner core of the NLC particles. The drug release behavior from the NLC displayed a biphasic drug release pattern with burst release at the initial stage followed by sustained release. These results indicated that the NLC3 is a suitable carrier of minoxidil with improved drug loading capacity and controlled drug release properties. It has been observed that NLC gel produces the gel with good consistency, homogeneity, spreadability and rheological behavior. The developed NLC-based gel showed faster onset and elicited prolonged activity up to 16 h. The present study concluded that the NLC-based gel containing minoxidil dissolved in a mixture of solid lipid and liquid lipid in the nanoparticulate form helped us to attain the objective of faster onset yet prolonged action as evident from in vitro release.     

Cetyl palmitate-based NLC for topical delivery of Coenzyme Q(10) - development, physicochemical characterization and in vitro release studies.

In the present study, nanostructured lipid carriers (NLC) composed of cetyl palmitate with various amounts of caprylic/capric triacylglycerols (as liquid lipid) were prepared and Coenzyme Q(10) (Q(10)) has been incorporated in such carriers due to its high lipophilic character. A nanoemulsion composed solely of liquid lipid was prepared for comparison studies. By photon correlation spectroscopy a mean particle size in the range of 180-240nm with a narrow polydispersity index (PI) lower than 0.2 was obtained for all developed formulations. The entrapment efficiency was 100% in all cases. The increase of oil loading did not affect the mean particle size of NLC formulations. NLC and nanoemulsion, stabilized by the same emulsifier, showed zeta potential values in the range -40/-50mV providing a good physical stability of the formulations. Scanning electron microscopy studies revealed NLC of disc-like shape. With respect to lipid polymorphism, a decrease in the ordered structure of NLC was observed with the increase of both oil and Q(10) loadings, allowing therefore high accommodation for Q(10) within the NLC. Using static Franz diffusion cells, the in vitro release studies demonstrated that Q(10)-loaded NLC possessed a biphasic release pattern, in comparison to Q(10)-loaded nanoemulsions comprising similar composition of which a nearly constant release was observed. The NLC release patterns were defined by an initial fast release in comparison to the release of NE followed by a prolonged release, which was dependent on the oil content.     

Liquid and semisolid SLN dispersions for topical application: rheological characterization.

Aqueous dispersions of solid lipid nanoparticles (SLN) are promising drug carrier systems for topical application. A drawback, however, is the need of incorporating the SLN dispersion in commonly used dermal carriers (creams, gels) to obtain the required semisolid consistency for dermal application. This study describes the production of SLN dispersions having the desired semisolid consistency by a one-step process. Physical characterization of these systems in terms of particle size and rheological properties revealed some interesting features. Despite the high lipid content it was possible to produce colloidal dispersions by high pressure homogenization. Continuous flow measurements revealed systems with yield point, plastic flow and thixotropy. Oscillation measurements proved the viscoelastic microstructure of the SLN dispersions. Higher concentrated SLN dispersions were found to have a prevailing elastic component in contrast to lower concentrated systems. Viscoelastic properties of a 40% SLN dispersion were found to be comparable to standard dermal preparations. Storage stability at room temperature in terms of particle size could be demonstrated over a 6-month period. The development of the gel structure of semisolid SLN dispersions is delayed comparable to commercial O/W creams with non-ionic emulsifiers. Parameters like concentration of the dispersed phase, particle size and particle shape were identified as significant factors influencing the microstructure of these complex semisolid systems.