SLN Dispersions Research Articles

Development of ibuprofen-loaded solid lipid nanoparticle-based hydrogels for enhanced in vitro dermal permeation and in vivo topical anti-inflammatory activity

In this study, hydrogels containing ibuprofen-loaded solid lipid nanoparticles (IBU-loaded SLNs) were developed to enhance the skin penetration of ibuprofen and for the local treatment of inflammation in experimental rats. IBU-loaded SLNs were prepared using cetostearyl alcohol as a solid lipid material in the oil phase, Tween 80 as an emulsifier in the aqueous phase, and NaOH as a solubilization enhancer. The optimized IBU-loaded SLN dispersions were also characterized according to the average particle size (from 98 ± 3 nm to 101 ± 1 nm), polydispersity index (from 0.119 ± 0.004 to 0.181 ± 0.019), zeta potential (from −2.66 ± 0.14 mV to −3.46 ± 0.75 mV), and encapsulation efficiency (from 56.88% to 58.89%). The gelling agent xanthan gum showed a crucial role in forming a homogeneous and stable network for incorporating and maintaining IBU-loaded SLNs on the skin, as examined via scanning electron microscopy and rheological properties analysis. Subsequently, IBU-loaded SLN-based hydrogels with an IBU:cetostearyl alcohol ratio of 1:1 exhibited the highest enhancement of in vitro permeation through the skin (a flux of 529.67 μg/cm2/h) and efficacy in treating inflammation in rats, compared with other prepared hydrogels and the commercial product Nurofen® 5% Gel.

Influence of spray drying on the stability of food-grade solid lipid nanoparticles

This study investigated spray drying of food-grade solid lipid particles (SLN) and nanostructured lipid carriers (NLC) containing ω-3 fish oil. Stable SLN and NLC dispersions with tristearin as carrier lipid were formed by using a combination of Quillaja saponins and high-melting lecithin as emulsifiers. Our specific goal was to study the influence of four different spray drying inlet and outlet temperatures (Tinlet/outlet = 140–170 °C/65–95 °C) and two different maltodextrin types (DE 6 and DE 21) with different molecular weights as protective wall materials on the physical and polymorphic stability of the solid lipid particles. The results revealed that the low molecular weight maltodextrin DE 21 was a superior wall material in stabilizing the solid lipid particles. Moreover, the lipid particles spray dried at Tinlet/outlet of 140/65 °C exhibited the highest physical and polymorphic stability, whereas using higher Tinlet/outlet led to bigger particles which were more prone to polymorphic transition. This was also verified in a 71-day storage test. The findings were explained that by preventing the melting of the tristearin carrier lipid during spray drying, the crystallized lipid particles remained intact inside the amorphous maltodextrin layer and exhibited high physical and polymorphic stability. These findings are important for generating stable food-grade spray dried powders.

Novel Drug Delivery System for Dermal Uptake of Etofenamate: Semisolid SLN Dispersion.

Semisolid SLNs are novel strategy for dermal drug administration instead of incorporating the SLN dispersions into conventional semisolids. Etofenamate loaded semisolid SLNs were successfully prepared and in vitro characterization of formulations were performed in our previous study. The present study is an attempt to evaluate the dermal behavior of the semisolid SLNs selected on the basis of previous research and investigate the properties in terms of the convenience for topical applications. The objective of this study is to evaluate the skin penetration characteristics of semisolid SLN formulations. The occlusive and mechanical properties of semisolid SLNs were also evaluated because of their impression on the dermal behavior of the formulations. The occlusive properties were investigated by in vitro occlusion test. Texture analysis was performed to define the hardness, compressibility, adhesiveness, cohesiveness and elasticity of the formulations. Rat skin was chosen to evaluate the ex vivo penetration of etofenamate loaded semisolid SLNs and commercial gel product. Coumarin-6 was used to visualize the dermal distribution of the semisolid SLN formulations. For monitorizing the penetration of coumarin-6 into the skin samples Confocal Laser Scanning Microscopy was employed. The occlusive and mechanical properties of C1 coded semisolid SLN formulation were found more favorable in comparison with P1. The cumulative etofenamate amount in skin samples was found to be 39.88 ± 1.50 μg/cm2 for C1 and 30.56 ± 2.10 μg/cm2 for P1 coded formulations. According to CLSM images, greater fluorescence intensities and deeper skin penetrations were obtained with both of the semisolid SLNs in comparison to plain Carbopol gel. It can be concluded that the semisolid SLNs are promising alternative dermal drug delivery systems to the conventional dosage forms.

Compatibility study In-vitro drug release Study of Solid Lipid Nanoparticle Based Transdermal Drug Delivery System for Rasagiline Mesylate

Transdermal drug delivery system (TDDS) is the dosage forms which deliver a therapeutically effective amount of drug across a patient's skin. The Solid lipid nanoparticles were successfully developed for rasagiline mesylate. SLN dispersions were prepared by melt emulsification and solidification at low temperature method. Compatibility between Drug and polymer study by FTIR. DSC and in-vitro release profile were carried out. In the Transdermal Drug Delivery System, Formulations F1-F9 was prepared by solvent casting method using 1.5%, 2.5% and 3.5% of HPMC K4M and 20%, 30% and 40% (w/w of dry polymer) of PEG 400. The formulation F5 was selected as the promising formulation on the basis of cumulative % drug release. The cumulative % drug diffused of F5 was found to be 89.55 ± 1.983. Further, the patch was found to be free of skin irritation. From the results stability study it can be concluded that the patches can be stored at 40°C and 75% RH without any significant stability problems. The formulation satisfied all the pharmaceutical parameters of transdermal films and appears to be promising.

Solid lipid nanoparticles for encapsulation of hydrophilic drugs by an organic solvent free double emulsion technique

Encapsulation of hydrophilic compounds for drug delivery systems with high loading efficiency is not easily feasible and remains a challenge, mainly due to the leaking of the drug to the outer aqueous phase during nanoparticle production. Usually, encapsulation of hydrophilic drugs is achieved by using double emulsion or inverse miniemulsion systems that often require the use of organic solvents, which may generate toxicological issues arising from solvent residues. Herein, we present the preparation of solid lipid nanoparticles loaded with a hydrophilic compound by a novel organic solvent free double emulsion/melt dispersion technique. The main objective of this study was to investigate the influence of important process and formulation variables, such as lipid composition, surfactant type, sonication parameters and lipid solidification conditions over physicochemical characteristics of SLN dispersion. Particle size and dispersity, as well as dispersion stability were used as responses. SLN dispersions with average size ranging from 277 to 550nm were obtained, showing stability for over 60 days at 4°C depending on the chosen emulsifying system. Entrapment efficiency of fluorescent dyes used as model markers was assessed by fluorescence microscopy and UV–vis spectrophotometry and results suggest that the obtained lipid based nanoparticles could be potentially applied as a delivery system of water soluble drugs.

The effect of formulative parameters on the size and physical stability of SLN based on “green” components

Cocoa butter (CB) is a largely used excipient in pharmaceutical field. Aim of this work was to set formulative parameters for the preparation of SLN based on “green” lipid matrix for drug delivery as natural, both human and environmental safe systems. Double emulsion technique (w1/o/w2) was selected for SLN preparation. The effect on the dimensional properties of different surfactants (Tween 80 and PEG 40 monostearate) and co-surfactants (PEG400 monostearate, Emulium® Kappa2 and Plurol®Stearique) at different concentrations was evaluated. Stability tests were performed. SLN dispersions were exsiccated and the effect of the dried process on SLN size was evaluated. The influence of temperature on SLN dimensions was investigated at 37 °C. MTT test was performed on raw materials and formulations. The w1/o/w2 is suitable, rapid and economic technique for the preparation of CB SLN. Tween 80-Plurol Stearique combination gives the best results: particles size less than 400 nm and PI of about 0.4 are obtained when PS 2% is used. Both raw materials and formulations are safe. The importance to evaluate the effect of different surfactant and/or co-surfactant on the dimensional properties of SLN is evident by selecting substances with preferable safety profiles, and favorable environmental properties to develop stable “green” SLN.

Engineering of phosphatidylcholine-based solid lipid nanocarriers for flavonoids delivery

The present study has been focused on determination and evaluation of three different preparation techniques, i.e., solvent-diffusion, hot homogenization-ultrasonification and microemulsification, applied in fabrication of biocompatible phosphatidylcholine solid lipid nanoparticles ((PC)-SLNs), containing Polawax National Formulary (NF) in the internal lipid phase. The fabricated lipid nanoparticles were loaded with the newly synthesized flavonoid cocrystals, i.e., baicalein–nicotinamide (1:1) (BaiNam), myricetin–piracetam (1:1) (MyrPac) and myricetin–caffeine (1:1) (MyrCaf) cocrystals in relation to the starting flavonoids, differing in solubility and physical state. The assessment of all studied drugs entrapment and availability in aqueous SLN dispersions has been carried out; the size along with size distribution of lipid nanoparticles loaded with the studied flavonoids cocrystals and flavonoids was determined by the DLS technique, while the structural changes—by FT-IR spectroscopy and X-ray powder diffraction (XRPD) of the lipid nanomatrices. XRPD and FT-IR analyses confirmed that parent flavonoids as well as their cocrystals are present in the nanoparticles fabricated with solvent-diffusion method as physical mixtures with the lipid and their crystalline structures at least partially conserved. Summarizing, we designed and fabricated the biocompatible SLN-type nanocarriers of enhanced physical stability and availability for the flavonoids delivery—a vast group of naturally occurring polyphenolic compounds, considered as active pharmaceutical ingredients.

Preparation, characterization and scale-up of sesamol loaded solid lipid nanoparticles

Sesamol loaded solid lipid nanoparticles (SSLNs) were prepared with the aim of minimizing its distribution to tissues and achieving its targeting to the brain. Three scale-up batches (100x1 L) of S-SLNs were prepared using a microemulsification technique and all parameters were statistically compared with the small batch (1x;10 mL). S-SLNs with a particle size of less than 106 nm with a spherical shape (transmission electron microscopy) were successfully prepared with a total drug content and entrapment efficiency of 94.26±2.71% and 72.57±5.20%, respectively. Differential scanning calorimetry and infrared spectroscopy confirmed the formation of lipidic nanoparticles while powder X-ray diffraction revealed their amorphous profile. S-SLNs were found to be stable for three months at 5±3°C in accordance with International Conference on Harmonisation guidelines. The SLN preparation process was successfully scaled-up to a 100x batch on a laboratory scale. The procedure was easy to perform and allowed reproducible SLN dispersions to be obtained.

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.

Atorvastatin Loaded Solidlipid Nanoparticles: Formulation, Optimization, and in - vitro Characterization

–This study describes the formulation of Atorvastatin (ATRS) loaded solid lipid nanoparticles by hot homogenization fallowed by ultrasonication technique, and optimization of formulation and process parameters to formulate preferred SLN dispersions. The effects of composition of lipid materials, surfactant mixture and sonication time on particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated The mean particles size, PDI, zeta potential and entrapment efficiency of optimized formulation (A5) was found to be 50.0± 6.12 nm, 0.08±0.011,10.40± 4.68mV, 88.7± 6.08 % respectively. To characterize the state of drug and lipid modification in ATRS loaded solidlipid nanoparticles, differential scanning calorimetry analysis was performed. Shape and surface morphology was determined by Transmission Electron Microscopy (TEM) which revealed fairly spherical shape of nanoparticles. The in-vitro drug release study demonstrated that ATRS-SLN formulation (A5) possessed controlled drug release over a period of 24 hrs than dispersion of pure drug. Stability studies performed on the selected formulations revealed that there was no physical instability of the developed formulation for a period of 3 months at room and refrigerated temperatures. Keywords––Solid lipid nanoparticles, Atorvastatin, Ultrasonication and Entrapment Efficiency

Characterization of Nigella Sativa L. Essential Oil-Loaded Solid Lipid Nanoparticles

Problem statement: Seeds of Nigella sativa L., commonly known as black seed, have been used in traditional medicine by many Asian, Middle Eastern and Far Eastern Countries to treat headache, coughs, abdominal pain, diarrhea, asthma, rheumatism and other diseases. The seeds of this plant are the most extensively studied, both phytoc hemically and pharmacologically. The aqueous and oil extracts of the seeds have been shown to posses s especially nowadays in pharmaceutical antioxidant, anti-inflammatory, anticancer, analges ic, antimicrobial activities and medicinal and cosmetic applications, sanitary, cosmetic, agricult ural and food industries. Approach: The aim of this study was to formulate a new delivery system for de rmal and cosmetic application by the incorporation of Nigella sativa essential oil into solid lipid nanoparticles SLN. S LN formulations were prepared following the high-pressure homogenization after st arring and ultra-trax homognization techniques using hydrogenated palm oil Softisan 154 and N. sativa essential oil as lipid matrix, sorbitol and water as surfactants. The SLN formulation particle size w as determined using Photon Correlation System (PCS). Results: The change of particle charge was studied by Zeta Potential (ZP) measurements, while the melting and re-crystallization behavior was stu died using Differential Scanning Calorimetry (DSC). Data showed a high physical stability for bo th formulations at various storage temperatures during 3 months of storage. In particu lar, average diameter of N. sativa essential oil- loaded SLN did not vary during storage and increase d slightly after freeze-drying the SLN dispersions. Conclusion: Therefore, obtained results showed that the studie d SLN formulations are suitable carriers in pharmaceutical and cosmetic fi elds.

Preparation and Evaluation of Miconazole Nitrate-Loaded Solid Lipid Nanoparticles for Topical Delivery

The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.

Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies

The aim of the study is to prepare aqueous dispersions of lipid nanoparticles – flurbiprofen solid lipid nanoparticles (FLUSLN) and flurbiprofen nanostructured lipid carriers (FLUNLC) by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1) and NLC gel (B1) for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 ± 2.77 μg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 ± 2.96 μg/ml). The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel

Influence of Polymorphic Transformations on Gelation of Tripalmitin Solid Lipid Nanoparticle Suspensions

AbstractSolid lipid nanoparticle (SLN) suspensions, which consist of submicron‐sized crystalline lipid particles dispersed within an aqueous medium, can be used to encapsulate, protect and deliver lipophilic functional components. Nevertheless, SLN suspensions are susceptible to particle aggregation and gelation during their preparation and storage, which potentially limits their industrial utilization. In this study, we examined the aggregation and gelation behavior of SLN suspensions composed of 10 wt% tripalmitin particles (r < 150 nm) stabilized by 1.5% Tween 20. The tripalmitin and aqueous surfactant solution were homogenized above the lipid melting temperature and cooled under controlled conditions to initiate SLN formation. The aggregation and gelation of SLN suspensions during storage was then examined by shear rheometry, differential scanning calorimetry (DSC), light scattering and microscopy. Rheology measurements indicated that gelation times decreased with increasing storage temperature, e.g., samples formed weak gels after 62, 23, and 10 min at 1, 5, and 10 °C, respectively. DSC revealed increasingly rapid α‐ to β‐polymorphic transformations in SLN dispersions stored at 1, 5, and 10 °C, respectively. We propose that the observed aggregation and gelation of SLN suspensions are associated with a change in the shape of the nanoparticles from spherical (α‐form) to non‐spherical (β‐form) when they undergo the polymorphic transition. When they change shape there is no longer sufficient surfactant present to completely cover the lipid phase, which promotes particle aggregation through hydrophobic attraction. Our results have important implications for the design and fabrication of stable SLN suspensions.

Development and evaluation of nitrendipine loaded solid lipid nanoparticles: Influence of wax and glyceride lipids on plasma pharmacokinetics

Nitrendipine is an antihypertensive drug with poor oral bioavailability ranging from 10 to 20% due to the first pass metabolism. For improving the oral bioavailability of nitrendipine, nitrendipine loaded solid lipid nanoparticles have been developed using triglyceride (tripalmitin), monoglyceride (glyceryl monostearate) and wax (cetyl palmitate). Poloxamer 188 was used as surfactant. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. SLN were characterized for particle size, zeta potential, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in phosphate buffer of pH 6.8 using Franz diffusion cell. Pharmacokinetics of nitrendipine loaded solid lipid nanoparticles after intraduodenal administration to conscious male Wistar rats was studied. Bioavailability of nitrendipine was increased three- to four-fold after intraduodenal administration compared to that of nitrendipine suspension. The obtained results are indicative of solid lipid nanoparticles as carriers for improving the bioavailability of lipophilic drugs such as nitrendipine by minimizing first pass metabolism.

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.

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 °C. These colloidal dispersions containing the sunscreen also exhibited the common melting behaviour of aqueous SLN dispersions.

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.

Vitamin A-loaded solid lipid nanoparticles for topical use: drug release properties

Burst release as well as sustained release has been reported for SLN suspensions. For dermal application, both features are of interest. Burst release can be useful to improve the penetration of a drug. Sustained release becomes important with active ingredients that are irritating at high concentrations or to supply the skin over a prolonged period of time with a drug. Glyceryl behenate SLN were loaded with vitamin A and the release profiles were studied. Franz diffusion cells were used to assess the release kinetic over a period of 24 h. Within the first 6 h retinol SLN displayed controlled release. After longer periods (12–24 h) the release rate increased and even exceeded the release rate of comparable nanoemulsions. Pure SLN dispersions are characterised by low viscosity. In contrast to membranous vesicles, SLN can also be stably incorporated in convenient topical dosage forms like hydrogels or creams. In the Franz diffusion cell these preparations showed a controlled release over 12–18 h. Similar to SLN dispersions an increase in release rate over a 24-h period was found. A good correlation between polymorphic transitions and increased drug release was observed in this study. Sustained release was often related to the metastable β′ polymorph. Drug expulsion is explained by a reduction of amorphous regions in the carrier lattice due to a β′→β i polymorphic transition. This transformation can be controlled with surfactant mixtures or, in the case of the hydrogel and oil/water cream, with humectants or gelling agents. Thus, the release rate for the topical route of application is adjustable.

Correlation between long-term stability of solid lipid nanoparticles (SLN™) and crystallinity of the lipid phase

Aqueous dispersions of solid lipid nanoparticles (SLN™) are usually physically stable for more than 3 years. However, in some systems gelation occurred leading to solid gels due to an unknown mechanism. To elucidate this mechanism, Compritol® SLN were stored at different temperatures, varying light exposure, in different packing materials and stressed by shear forces in short-term tests and a long-term study of 3 years. The SLN were analyzed by differential scanning calorimetry and sizing techniques. After production by hot homogenization of the melted lipid, the Compritol® SLN crystallize in a mixture of stable β′ with unstable polymorphs ( α, sub α). The destabilizing factors light, temperature and shear forces cause a distinct increase in the recrystallization index by transformation of the lipid to the β′ modification being accompanied by gel formation. Physically stable SLN remain as a mixture of modifications, increase in crystallinity index during storage is slow and crystallization occurs mainly in unstable modifications. From this, stabilization of physically critical SLN dispersions seems possible by inhibition of the transformation of the lipid to the stable modification.