Spherical Crystallization Based on Liquid-Liquid Phase Separation in a Reverse Antisolvent Crystallization Process.

Vanillin crystals undergo needle-like morphology that results in poor flowability, crystal breakage, and low packing density. The spherical crystallization technology can produce particles with improved flowability and stability. A reverse antisolvent crystallization based on liquid-liquid phase separation is proposed in this work to produce vanillin spherical agglomerates. Hansen Solubility Parameters are applied to explain the liquid-liquid phase separation (LLPS) phenomenon. The Pixact Crystallization Monitoring system is applied to in-situ monitor the whole process. A six-step spherical crystallization mechanism is revealed based on the recorded photos, including the generation of oil droplets, nucleation inside oil droplets, the coalescence and split of oil droplets, crystal growth and agglomeration, breakage of oil droplets, and attrition of agglomerates. Different working conditions are tested to explore the best operation parameters and a frequency-conversion stirring strategy is proposed to improve the production of spherical crystals.

Improvement and characterization of oral absorption behavior of clofazimine by SNEDDS: Quantitative evaluation of extensive lymphatic transport.

Clofazimine, an anti-leprosy drug, has been anticipated for a candidate to treat tuberculosis, cryptosporidiosis, and coronavirus infection, but its low oral bioavailability is considered a reason for its limited activity. In the current study, we have tried to improve the oral bioavailability of clofazimine by several SNEDDS formulations and characterized the absorption behavior from various aspects. Among four SNEDDS formulations prepared, SNEDDS A, prepared with castor oil as an oil component, provided the highest bioavailability (around 61%) and SNEDDS D, prepared with Capryol 90, gave the second highest bioavailability. SNEDDS A formed the finest nanoparticles, which were maintained under gastric and intestinal luminal conditions. The comparison in oral bioavailability between the SNEDDS formulation and its corresponding preformed nanoemulsion suggested that SNEDDS A would efficiently form nanoemulsion in the gastrointestinal tract after oral administration. AUC of mesenteric lymph node concentration was the highest for SNEDDS A, which would be one of the reasons for SNEDDS A to reveal the highest oral bioavailability. A cycloheximide-treated oral absorption study and single-pass perfusion study by utilizing a vascular-luminal perfused small intestine-liver preparation clearly indicated that over 90% of clofazimine absorbed to systemic circulation should be derived from lymphatic transport for both SNEDDS A and D. Furthermore, the fraction of dose absorbed was around 65% for SNEDDS D, but SNEDDS A achieved around 94%, indicating the excellent performance of SNEDDS A.

Effect of XlogP and hansen solubility parameters on the prediction of small molecule modified docetaxel, doxorubicin and irinotecan conjugates forming stable nanoparticles.

Small molecule-chemotherapeutic drug conjugate nanoparticles (SMCDC NPs) has a great advantage in improving drug loading. However, the factors which influence these conjugates forming stable nanoparticles (NPs) are currently unclear. In our previous studies, we synthesized a series of fatty acid-paclitaxel conjugates and suggested that the changes in the hydrophobic parameters (XlogP), solubility parameters and crystallinity of these fatty acid-paclitaxel conjugates were the key factors for affecting these small molecule-chemotherapeutic drug conjugates (SMCDCs) forming stable NPs in water. Here, we selected clinically widely used chemotherapeutic drug (docetaxel (DTX), doxorubicin (DOX) and irinotecan (Ir)) as model drug, and chose three straight-chain fatty acids (acetic acid (Ac), hexanoic acid (HA) and stearic acid (SA)) and one branched small molecule (N-(tert-butoxycarbonyl) glycine (B-G)) to synthesize 12 SMCDCs. Our results indicated that our prediction criterions obtained from paclitaxel conjugates were also appropriated for these synthesized SMCDCs. We suggested that the present studies expanded the scope of application of the above-mentioned influencing factors, provided research ideas for the rational design of SMCDC forming NPs and a basis for screening NPs with good anticancer activity.

Controllable Liquid Exfoliation of Fibrous Phosphorus and Its Live-Cell Imaging.

One-dimensional materials have been intensively studied because of their diverse properties, which are revealed when exfoliated from their bulk precursor. Liquid exfoliation is not only possibly the most suitable method for large-scale applications but also affords an opportunity to develop new deposition techniques. Fibrous phosphorus is a relatively new, one-dimensional material with high carrier mobility and a fast response velocity for future application in nanodevices. Because controllable liquid exfoliation processing of fibrous phosphorus (FP) remains challenging, we considered two factors: the exfoliated result and the removable solvents. We proposed a method for determining suitable solvents for efficient exfoliation and controllable size of fibrous phosphorus using Hansen solubility parameters. By controlling the water/acetone mixture ratios, the exfoliation effect could be controlled. Our work showed that 40% of the FP nanofibers were less than 10 nm in thickness and 70% of them were less than 20 nm. Furthermore, fibrous phosphorus produced a red fluorescence in bioimaging.

High-Throughput Synthesis and Screening of Rapidly Degrading Polyanhydride Nanoparticles.

Combinatorial techniques can accelerate the discovery and development of polymeric nanodelivery devices by pairing high-throughput synthesis with rapid materials characterization. Biodegradable polyanhydrides demonstrate tunable release, high cellular internalization, and dose sparing properties when used as nanodelivery devices. This nanoparticle platform shows promising potential for small molecule drug delivery, but the pace of understanding and rational design of these nanomedicines is limited by the low throughput of conventional characterization. This study reports the use of a high-throughput method to synthesize libraries of a newly synthesized, rapidly eroding polyanhydride copolymer based on 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and sebacic acid (SA) monomers. The high-throughput method enabled efficient screening of copolymer microstructure, revealing weak block-type and alternating architectures. The high-throughput method was adapted to synthesize nanoparticle libraries encapsulating hydrophobic model drugs. Drug release from these nanoparticles was rapid, with a majority of the payload released within 3 days. Drug release was dramatically slowed at acidic pH, which could be useful for oral drug delivery. Rhodamine B (RhoB) release kinetics generally followed patterns of polymer erosion kinetics, while Coomassie brilliant blue (CBB) released the fastest from the slowest degrading polymer chemistry and vice versa. These differences in trends between copolymer chemistry and release kinetics were hypothesized to arise from differences in mixing thermodynamics. A high-throughput method was developed to synthesize polymer-drug film libraries and characterize mixing thermodynamics by melting point depression. Rhodamine B had a negative χ for all copolymers with <30 mol % CPTEG tested, indicating a tendency toward miscibility. By contrast, CBB χ increased, eventually becoming positive near 15:85 CPTEG:SA, with increasing CPTEG content. This indicates an increasing tendency toward phase separation in CPTEG-rich copolymers. These in vitro results screening polymer-drug interactions showed good agreement with in silico predictions from Hansen solubility parameter estimation and were able to explain the observed differences in model drug release trends.

Formulation development of lipid nanoparticles: Improved lipid screening and development of tacrolimus loaded nanostructured lipid carriers (NLC).

Lipid nanoparticles are well-known nanocarriers for improved drug delivery. Their formulation development typically involves three formulations steps. In the first part a suitable lipid mixture which enables a high loading capacity and high encapsulation efficacy of the active needs to be identified (lipid screening). In the second step suitable stabilizers that enable the production of small-sized lipid nanoparticles with narrow size distribution and sufficient physical stability need to be identified (stabilizer screening, optimization of production parameters) and in the third step the biopharmaceutical efficacy needs to be evaluated. Based on the results obtained the formulations will require further optimization. The classical formulation development of lipid nanoparticles and especially the classical lipid screening is tedious. Therefore, in this study, a novel approach for the lipid screening that was based on the determination of the Hansen solubility parameters was evaluated and the results obtained were compared to the results from the classical model. Tacrolimus was used as a model drug. Results showed that both lipid screenings led to similar results, indicating that the new approach can be used for future developments. The optimized formulation was composed of a lipid matrix system that contained waxes, triglycerides and monoacylglycerols with various carbon chain lengths (C8, C10, C16, C18) and enabled an encapsulation efficiency of ~99%. The stabilizer screening showed that surfactants with high HLB values, lower molecular weight, and shorter alkyl chain length tended to form smaller particles with narrower size distribution and better physical stability. The most suitable surfactant was found to be a caprylyl/capryl glucoside (Plantacare® 810), a PEG-free stabilizer, that is extremely mild for atopic skin. It led to particle sizes of about 200 nm and a zeta potential well above |30| mV. The optimized formulation contained 0.1% tacrolimus and possessed good physical stability. In conclusion, an optimized method for the selection of lipids that results in a limited number of experiments could be established and tacrolimus loaded lipid nanoparticles with similar drug load as a marketed formulation was successfully developed in this study.

Experimental validation of biocompatible nanostructured lipid carriers of sophorolipid: Optimization, characterization and in-vitro evaluation.

To date, the potential of sophorolipids (an important class of glycolipids) has been exploited solely as amphipathic molecules but their ability to formulate lipid nanoparticles has never been explored. In this report, for the first time, lipid nanostructures coated with polysorbates (Tweens) were formulated by a hot dispersion method. By varying the amount of lipid, type of surfactant, and alcohol, dilution ratio etc., the formulation was optimized with respect to its stability, which is a central aspect of their potential applications. Their comprehensive physicochemical characterization was done using static and dynamic light scattering (SLS, DLS), small angle neutron scattering (SANS), zeta-potential, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques. Further hemolysis study was conducted to understand the in-vitro cytotoxicity levels of the lipidic nanoparticles prior to its application as a potent drug delivery device for countermanding the problems associated with challenging tuberculosis and leprosy drug-Rifampicin. Attaining high entrapment efficiency and sustained release from the developed carrier, further interaction with bovine serum albumin was investigated, to understand the in-vivo behavior of the nanostructured lipid carriers (NLCs).

Single Crystal FLIM Characterization of Clofazimine Loaded in Silica-Based Mesoporous Materials and Zeolites.

Clofazimine (CLZ) is an effective antibiotic used against a wide spectrum of Gram-positive bacteria and leprosy. One of its main drawbacks is its poor solubility in water. Silica based materials are used as drug delivery carriers that can increase the solubility of different hydrophobic drugs. Here, we studied how the properties of the silica framework of the mesoporous materials SBA-15, MCM-41, Al-MCM-41, and zeolites NaX, NaY, and HY affect the loading, stability, and distribution of encapsulated CLZ. Time-correlated single-photon counting (TCSPC) and fluorescence lifetime imaging microscopy (FLIM) experiments show the presence of neutral and protonated CLZ (1.3-3.8 ns) and weakly interacting aggregates (0.4-0.9 ns), along with H- and J-type aggregates (<0.1 ns). For the mesoporous and HY zeolite composites, the relative contribution to the overall emission spectra from H-type aggregates is low (<10%), while for the J-type aggregates it becomes higher (~30%). For NaX and NaY the former increased whereas the latter decreased. Although the CLZ@mesoporous composites show higher loading compared to the CLZ@zeolites ones, the behavior of CLZ is not uniform and its dynamics are more heterogeneous across different single mesoporous particles. These results may have implication in the design of silica-based drug carriers for better loading and release mechanisms of hydrophobic drugs.

Study the influence of formulation process parameters on solubility and dissolution enhancement of efavirenz solid solutions prepared by hot-melt extrusion: a QbD methodology.

The current study investigates the dissolution rate performance of amorphous solid solutions of a poorly water-soluble drug, efavirenz (EFV), in amorphous Soluplus® (SOL) and Kollidon® VA 64 (KVA64) polymeric systems. For the purpose of the study, various formulations with varying drug loadings of 30, 50, and 70% w/w were developed via hot-melt extrusion processing and adopting a Box-Behnken design of experiment (DoE) approach. The polymers were selected based on the Hansen solubility parameter calculation and the prediction of the possible drug-polymer miscibility. In DoE experiments, a Box-Behnken factorial design was conducted to evaluate the effect of independent variables such as Soluplus® ratio (A1), HME screw speed (A2), and processing temperature (A3), and Kollidon®VA64 ratio (B1), screw speed (B2), and processing temperature (B3) on responses such as solubility (X1 and Y1) and dissolution rate (X2 and Y2) for both ASS [EFV:SOL] and BSS [EFV:KVA64] systems. DSC and XRD data confirmed that bulk crystalline EFV transformed to amorphous form during the HME processing. Advanced chemical analyses conducted via 2D COSY NMR, FTIR chemical imaging, AFM analysis, and FTIR showed that EFV was homogenously dispersed in the respective polymer matrices. The maximum solubility and dissolution rate was observed in formulations containing 30% EFV with both SOL and KVA64 alone. This could be attributed to the maximum drug-polymer miscibility in the optimized formulations. The actual and predicted values of both responses were found precise and close to each other.

Hansen solubility parameters (HSP) for prescreening formulation of solid lipid nanoparticles (SLN): in vitro testing of curcumin-loaded SLN in MCF-7 and BT-474 cell lines.

Curcumin, a phenolic compound from turmeric rhizome (Curcuma longa), has many interesting pharmacological effects, but shows very low aqueous solubility. Consequently, several drug delivery systems based on polymeric and lipid raw materials have been proposed to increase its bioavailability. Solid lipid nanoparticles (SLN), consisting of solid lipid matrix and a surfactant layer can load poorly water-soluble drugs, such as curcumin, deliver them at defined rates and enhance their intracellular uptake. In the present work, we demonstrate that, despite the drug's affinity to lipids frequently used in SLN production, the curcumin amount loaded in most SLN formulations may be too low to exhibit anticancer properties. The predictive curcumin solubility in solid lipids has been thoroughly analyzed by Hansen solubility parameters, in parallel with the lipid-screening solubility tests for a range of selected lipids. We identified the most suitable lipid materials for curcumin-loaded SLN, producing physicochemically stable particles with high encapsulation efficiency (>90%). Loading capacity of curcumin in SLN allowed preventing the cellular damage caused by cationic SLN on MCF-7 and BT-474 cells but was not sufficient to exhibit drug's anticancer properties. But curcumin-loaded SLN exhibited antioxidant properties, substantiating the conclusions that curcumin's effect in cancer cells is highly dose dependent.

How Predictable Are Human Stratum Corneum Lipid/Water Partition Coefficients? Assessment and Useful Correlations for Dermal Absorption.

Partition coefficients between human stratum corneum lipids and water (Ksclip/w) are collected or deduced from a variety of sources in a manner that approximately doubles the available data compared to the current state-of-the-art model (Hansen et al., Adv Drug Deliv Rev. 2013;65(2):251-264). An additional datum for water itself in porcine SC that considerably extends the molecular size and lipophilicity range of the data set is considered. The data are analyzed in terms of an extended linear free energy relationship involving octanol/water partition coefficients, Abraham solvation parameters, and a secondary, power law molecular weight dependence. The optimum fit to log Ksclip/w for the full data set reduces the standard error of prediction from 0.50 for a Hansen-like model to 0.39; corresponding multiplicative errors in Ksclip/w are reduced from a factor of 3.1 to one of 2.5. The difference in performance is driven by the water datum, which requires a more complex dependence on molecular size than that afforded by Abraham parameters. In the absence of the water value, the Hansen-like model, which does not include a dependence on molecular size, is essentially optimum. A comparison is presented to fluid-phase phospholipid-water systems, which have a demonstrably different structure-property relationship.

pH-sensitive nanoparticles for improved oral delivery of dapsone: risk assessment, design, optimization and characterization.

AIM: To optimize the production of pH-sensitive dapsone (DAP) nanoparticles based on Eugradit L100 (NPs-EL100-DAP) for oral delivery. MATERIALS & METHODS: NPs-EL100-DAP were optimized using a Plackett-Burman design and a Box-Behnken design. The physicochemical properties of the obtained nanoparticles were monitored by microscopy, dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, in vitro release assays, and examined for cytotoxicity and permeation across intestinal barrier. RESULTS: The in vitro release assay of NPs-EL100-DAP confirmed the nanoparticles' pH sensitivity and the ability to deliver DAP at intestinal environment. NPs-EL100-DAP demonstrated enhanced intestinal interactions in comparison to free DAP, across Caco-2 monolayers. CONCLUSION: These studies demonstrate the potential of NPs-EL100-DAP as a therapeutic platform for oral treatment of leprosy.

Particle formation induced by sonication during yogurt fermentation - Impact of exopolysaccharide-producing starter cultures on physical properties.

Two major quality defects of yogurt are syneresis and the presence of large particles, and several reasons have been extensively discussed. Vibrations during fermentation, particularly generated by pumps, must be considered as a further cause as latest research showed that both ultrasound and low frequencies induced visible particles. The aim of this study was to investigate the impact of sonication during fermentation with starter cultures differing in exopolysaccharide (EPS) synthesis on the physical properties of set (syneresis, firmness) and stirred yogurt (large particles, laser diffraction, rheology). Skim milk was fermented with starter cultures YC-471 (low EPS) or YF-L 901 (high EPS) (Chr. Hansen) and sonicated for 5min at pH5.2. Sonicated set gels exhibited syneresis and were softer than respective controls. The mechanical treatment was adjusted to quantify visible particles (d≥0.9mm) in stirred yogurts properly. Sonication significantly increased particle numbers, however, the effect was less pronounced when YF-L 901 was used, indicating EPS as a tool to reduce syneresis and particle formation due to vibrations. Rheological parameters and size of microgel particles were rather influenced by starter cultures than by sonication.

Exploring the effect of hydrophilic and hydrophobic structure of grafted polymeric micelles on drug loading.

The objective of this paper is to explore the effect of hydrophilic and hydrophobic structure of grafted polymeric micelles on drug loading, and elucidate whether drug-polymer compatibility, as predicted by Hansen solubility parameters (HSPs), can be used as a tool for drug-polymer pairs screening and guide the design of grafted polymeric micelles. HSPs of 27 drugs and three grafted copolymers were calculated according to group contribution method. The drug-polymer compatibilities were evaluated using the approaches of Flory-Huggins interaction parameters (χFH) and polarity difference (△Xp). Two models, model A and B, were put forward for drug-polymer compatibility prediction. In model A, hydrophilic/hydrophobic part as a whole was regarded as one segment. And, in model B, hydrophilic and hydrophobic segments were evaluated individually. First of all, using chitosan (CS)-grafted-glyceryl monooeate (GMO) based micelle as an example, the suitability of model A and model B for predicating drug-polymer compatibility was evaluated theoretically. Thereafter, corresponding experiments were carried out to check the validity of the theoretical prediction. It was demonstrated that Model B, which evaluates drug compatibility with both hydrophilic and hydrophobic segments of the copolymer, is more reliable for drug-polymer compatibility prediction. Moreover, the approach of model B allows for the selection of a defined grafted polymer with for a specific drug and vice versa. Thus, drug compatibility evaluation via HSPs with both hydrophilic and hydrophobic segments is a suitable tool for the rational design of grafted polymeric micelles. The molecular dynamics (MD) simulation study provided further support to the established model and experimental results.

Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells.

The aim of the present work was to develop and optimize surface-functionalized solid lipid nanoparticles (SLNs) for improvement of the therapeutic index of dapsone (DAP), with the application of a design of experiments. The formulation was designed to target intestinal microfold (M-cells) as a strategy to increase internalization of the drug by the infected macrophages. DAP-loaded SLNs and mannosylated SLNs (M-SLNs) were successfully developed by hot ultrasonication method employing a three-level, three-factor Box-Behnken design, after the preformulation study was carried out with different lipids. All the formulations were systematically characterized regarding their diameter, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity. They were also subjected to morphological studies using transmission electron microscopy, in vitro release study, infrared analysis (Fourier transform infrared spectroscopy), calorimetry studies (differential scanning calorimetry), and stability studies. The diameter of SLNs, SLN-DAP, M-SLNs, and M-SLN-DAP was approximately 300 nm and the obtained PDI was <0.2, confirming uniform populations. Entrapment efficiency and loading capacity were approximately 50% and 12%, respectively. Transmission electron microscopy showed spherical shape and nonaggregated nanoparticles. Fourier transform infrared spectroscopy was used to confirm the success of mannose coating process though Schiff's base formation. The variation of the ZP between uncoated (approximately -30 mV) and mannosylated formulations (approximately +60 mV) also confirmed the successful coating process. A decrease in the enthalpy and broadening of the lipid melting peaks of the differential scanning calorimetry thermograms are consistent with the nanostructure of the SLNs. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. Storage stability for the formulations for at least 8 weeks is expected, since they maintain the original characteristics of diameter, PDI, and ZP. These results pose a strong argument that the developed formulations can be explored as a promising carrier for treating leprosy with an innovative approach to target DAP directly to M-cells.

The Influence of Sugar Cane Bagasse Type and Its Particle Size on Xylose Production and Xylose-to-Xylitol Bioconversion with the Yeast Debaryomyces hansenii.

In the present study, the effect of the type of sugar cane bagasse (non-depithed or depithed) and its particle size on the production of xylose and its subsequent fermentation to xylitol by Debaryomyces hansenii CBS767 was investigated using a full factorial experimental design. It was found that the particle size range and whether bagasse was depithed or not had a significant effect on the concentration and yield of xylose in the resulting hemicellulose hydrolysate. Depithed bagasse resulted in higher xylose concentrations compared to non-depithed bagasse. The corresponding detoxified hemicellulose hydrolysates were used as fermentation media for the production of xylitol. The hemicellulose hydrolysate prepared from depithed bagasse also yielded meaningfully higher xylitol fermentation rates compared to non-depithed bagasse. However, in the case of non-depithed bagasse, the hemicellulose hydrolysate prepared from larger particle size range resulted in higher xylitol fermentation rates, whereas the effect in the case of non-depithed bagasse was not pronounced. Therefore, depithing of bagasse is an advantageous pretreatment when it is to be employed in bioconversion processes.

Comparison of the cohesion-adhesion balance approach to colloidal probe atomic force microscopy and the measurement of Hansen partial solubility parameters by inverse gas chromatography for the prediction of dry powder inhalation performance.

The abilities of the cohesive-adhesive balance approach to atomic force microscopy (AFM) and the measurement of Hansen partial solubility parameters by inverse gas chromatography (IGC) to predict the performance of carrier-based dry powder inhaler (DPI) formulations were compared. Five model drugs (beclometasone dipropionate, budesonide, salbutamol sulphate, terbutaline sulphate and triamcinolone acetonide) and three model carriers (erythritol, α-lactose monohydrate and d-mannitol) were chosen, giving fifteen drug-carrier combinations. Comparison of the AFM and IGC interparticulate adhesion data suggested that they did not produce equivalent results. Comparison of the AFM data with the in vitro fine particle delivery of appropriate DPI formulations normalised to account for particle size differences revealed a previously observed pattern for the AFM measurements, with a slightly cohesive AFM CAB ratio being associated with the highest fine particle fraction. However, no consistent relationship between formulation performance and the IGC data was observed. The results as a whole highlight the complexity of the many interacting variables that can affect the behaviour of DPIs and suggest that the prediction of their performance from a single measurement is unlikely to be successful in every case.

A rapid screening assay for identifying mycobacteria targeted nanoparticle antibiotics.

Antibiotic resistance is a serious problem. Nanotechnology offers enormous potential in medicine, yet there is limited knowledge regarding the toxicity of nanoparticles (NP) for mycobacterial species that cause serious human diseases (e.g. tuberculosis (TB) and leprosy). Mycobacterial diseases are a major global health problem; TB caused by Mycobacterium tuberculosis (Mtb) kills up to 2 million people annually and there are over 200 000 leprosy cases each year caused by Mycobacterium leprae (M. leprae). Few drugs are effective against these mycobacteria and increasing antibiotic resistance exacerbates the problem. As such, alternative therapies are urgently needed but most current assays used to assess the effectiveness of therapeutics against mycobacteria are slow and expensive. This study aimed to develop a rapid, low-cost assay which can be used for screening the antimicrobial properties of compounds against pathogenic mycobacteria and to assess the toxicity of three NP (silver [Ag], copper oxide [Cu(II)O], and zinc oxide [ZnO]) against a green fluorescent protein reporter strain of Mycobacterium avium subspecies paratuberculosis, a slow growing, pathogenic mycobacterial species causing paratuberculosis in ruminants. Fluorescence was used to monitor mycobacterial growth over time, with NP concentrations of 6.25-100 µg/mL tested for up to 7 days, and a method of data analysis was designed to permit comparison between results. Mycobacterial sensitivity to the NP was found to be NP composition specific and toxicity could be ranked in the following order: Ag > Cu(II)O > ZnO.

Freezing lines of colloidal Yukawa spheres. II. Local structure and characteristic lengths.

Using the Rogers-Young (RY) integral equation scheme for the static pair correlation functions combined with the liquid-phase Hansen-Verlet freezing rule, we study the generic behavior of the radial distribution function and static structure factor of monodisperse charge-stabilized suspensions with Yukawa-type repulsive particle interactions at freezing. In a related article, labeled Paper I [J. Gapinski, G. Nägele, and A. Patkowski, J. Chem. Phys. 136, 024507 (2012)], this hybrid method was used to determine two-parameter freezing lines for experimentally controllable parameters, characteristic of suspensions of charged silica spheres in dimethylformamide. A universal scaling of the RY radial distribution function maximum is shown to apply to the liquid-bcc and liquid-fcc segments of the universal freezing line. A thorough analysis is made of the behavior of characteristic distances and wavenumbers, next-neighbor particle coordination numbers, osmotic compressibility factor, and the Ravaché-Mountain-Streett minimum-maximum radial distribution function ratio.

Nanoemulsion containing dapsone for topical administration: a study of in vitro release and epidermal permeation.

BACKGROUND: Topical administration of dapsone can be an alternative route for treatment of leprosy and can also provide new therapeutic applications for an established drug. However, the physicochemical properties of dapsone make it difficult to incorporate into conventional formulations. The current study was directed toward developing a stable nanoemulsion that contains dapsone which can be adapted for topical use. METHODS: Nanoemulsions were prepared using isopropyl myristate or n-methyl-pyrrolidone as the oil phase, and characterized according to their mean droplet size, conductivity, refractive index, pH, drug content, and stability. The in vitro release of dapsone and its ability to permeate the epidermis were also evaluated. RESULTS: Physicochemical characterization demonstrated that nanosystems were formed, which had a uniform droplet distribution and a pH compatible with the skin surface. Use of n-methyl-pyrrolidone provided a greater nanoemulsion region and higher solubilization of dapsone, and increased the in vitro release rate when compared with a nanoemulsion prepared using isopropyl myristate. However, use of isopropyl myristate promoted an increase in in vitro epidermal permeation that followed the Higuchi model. This demonstrates the ability of a nanosystem to influence permeation of dapsone through the skin barrier. Furthermore, the nanoemulsions developed and evaluated here had ideal physicochemical stability over a 3-month period. CONCLUSION: Incorporation of dapsone into a nanoemulsion may be a promising system for enabling topical delivery of dapsone, while minimizing skin permeation, for the treatment of acne. The method developed here used isopropyl myristate as the oil phase, and promoted permeation of dapsone through the skin barrier for the treatment of leprosy upon use of n-methyl-pyrrolidone as the oil phase.