Design,Optimization, and Evaluation of Lurasidone Hydrochloride Nanocrystals

The present investigation was carried out to design, optimize, and evaluate lurasidone hydrochloride nanocrystals for improving its solubility and dissolution characteristics. Nanocrystals were prepared by media milling technique using zirconium oxide beads with 0.1 mm diameter. Various stabilizers, viz. poloxamer 188, PVP K30, SLS, HPMC E15, and PVP S 630 D, were evaluated to stabilize the nanocrystals. The Pareto chart obtained through Plackett-Burman screening design revealed that HPMC E 15 showed the highest standardized effect (p value <0.05) on percent dissolution efficiency at 2 min. In subsequent studies, a 3² factorial design was employed to quantify the effect of two independent variables, namely amount of stabilizer and milling time on predetermined response variables mean particle size, saturation solubility, and percent dissolution efficiency at 2 min. Statistical analysis of the factorial design revealed that all predetermined response variables were significantly dependent (p value <0.05) on the independent variables. The observed response of the optimized batch prepared as per the desirability function was in close agreement with predicted response, and mathematical model generated was validated. The optimized batch was lyophilized, and X-ray powder diffraction studies indicated that there was no substantial change in crystallinity of the drug. The optimized formulation showed mean particle size of 228 nm and released almost all the drug within first 5 min. Since the crystallinity of the drug is maintained, improvement in saturation solubility and dissolution efficiency could be attributed to decrease in mean particle size of the drug.     

Design and Evaluation of Novel Solid Self-Nanodispersion Delivery System for Andrographolide

Poorly water-soluble drugs offer challenges in developing a formulation product with adequate bioavailability. This study took advantage of the features of nanocrystals and direct compression technologies to develop a novel solid self-nanodispersion delivery system for andrographolide (Andro) in order to increase its dissolution rate for enhancing bioavailability. Andro nanosuspensions (Andro-NS) with a particle size of about 500 nm were prepared by homogenization technology and further converted into dried nanocrystal particles (Andro-NP) via spray-drying. The solid self-nanodispersion delivery system (Andro-SNDS)-loaded Andro-NP was prepared via direct compression technology. The DSC and PXRD results demonstrated that the Andro nanocrystals retained its original crystallinity. The dissolution of the Andro-SNDS formulation was 85.87% in pure water over 30 min, better than those of the coarse Andro and physical mixture of Andro and stabilizer. And the C _max (299.32?±?78.54 ng/mL) and AUC_0-∞ (4440.55?±?764.13 mg/L?·?h) of the Andro-SNDS formulation were significantly higher (p?<?0.05) than those of the crude Andro (77.52?±?31.73 ng/mL and 1437.79?±?354.25 mg/L?·?h). The AUC of the Andro-SNDS was 3.09 times as high as that of the crude Andro. This study illustrated a novel approach to combine the features of nanocrystals and composite particles used to improve oral bioavailability of poorly soluble drug.     

Preparation and Evaluation of Diosgenin Nanocrystals to Improve Oral Bioavailability

Diosgenin (DSG), a well-known steroid sapogenin derived from Dioscorea nipponica Makino and Dioscorea zingiberensis Wright, has a variety of bioactivities. However, it shows low oral bioavailability due to poor aqueous solubility and strong hydrophobicity. The present study aimed to develop DSG nanocrystals to increase the dissolution and then improve the oral bioavailability and biopharmaceutical properties of DSG. DSG nanocrystals were prepared by the media milling method using a combination of pluronic F127 and sodium dodecyl sulfate as surface stabilizers. The physicochemical properties of the optimal DSG nanocrystals were characterized using their particle size distribution, morphology, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy data, and solubility and dissolution test results. Pharmacokinetic studies of the DSG coarse suspension and its nanocrystals were performed in rats. The particle size and polydispersity index of DSG nanocrystals were 229.0?±?3.7 nm and 0.163?±?0.064, respectively. DSG retained its original crystalline state during the manufacturing process, and its chemical structure was not compromised by the nanonizing process. The dissolution rate of the freeze-dried DSG nanocrystals was significantly improved in comparison with the original DSG. The pharmacokinetic studies showed that the AUC_0–72h and C _max of DSG nanocrystals increased markedly (p?<?0.01) in comparison with the DSG coarse suspension by about 2.55- and 2.01-fold, respectively. The use of optimized nanocrystals is a good and efficient strategy for oral administration of DSG due to the increased dissolution rate and oral bioavailability of DSG nanocrystals.     

An Intensified Vibratory Milling Process for Enhancing the Breakage Kinetics during the Preparation of Drug Nanosuspensions

As a drug-sparing approach in early development, vibratory milling has been used for the preparation of nanosuspensions of poorly water-soluble drugs. The aim of this study was to intensify this process through a systematic increase in vibration intensity and bead loading with the optimal bead size for faster production. Griseofulvin, a poorly water-soluble drug, was wet-milled using yttrium-stabilized zirconia beads with sizes ranging from 50 to 1500 μm at low power density (0.87 W/g). Then, this process was intensified with the optimal bead size by sequentially increasing vibration intensity and bead loading. Additional experiments with several bead sizes were performed at high power density (16 W/g), and the results were compared to those from wet stirred media milling. Laser diffraction, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and dissolution tests were used for characterization. Results for the low power density indicated 800 μm as the optimal bead size which led to a median size of 545 nm with more than 10% of the drug particles greater than 1.8 μm albeit the fastest breakage. An increase in either vibration intensity or bead loading resulted in faster breakage. The most intensified process led to 90% of the particles being smaller than 300 nm. At the high power intensity, 400 μm beads were optimal, which enhanced griseofulvin dissolution significantly and signified the importance of bead size in view of the power density. Only the optimally intensified vibratory milling led to a comparable nanosuspension to that prepared by the stirred media milling.     

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

The air-jet and ball-mill are frequently used in fine micronization of active pharmaceutical ingredients to the order of 1–5 μm, which is important for increasing dissolution rates, and also for pulmonary delivery. In this study, we investigated the ability of air-jet and ball-mill to achieve adequate micronization on the lab scale using a model soft material, Pluronic® F-68. Material mechanical properties were characterized using the nanometer 600. Pluronic® F-68 was ball-milled in a micro-mill at different material weights and durations in liquid nitrogen vapor. In comparison, a lab scale air-jet mill was used at various milling parameters according to a full factorial design, where the response factors were particle yield and particle size distribution, which was analyzed using laser diffraction and scanning electron microscopy. The yield achieved with the micro-ball mill was 100% but was ~80% for the air-jet mill, which reduced the size of Pluronic® F-68 from 70 μm to sizes ranging between 23–39 μm median diameters. Ball milling produced particles less than 10 μm after 15 min. Although air-jet milling proved capable of particle size reduction of the relatively soft material Pluronic® F-68, limitations to the lower size range achievable were observed. The feed rate of the material into the air jet mill was a significant factor and slower feed rates lead to smaller sizes by allowing more time for particle collisions and subsequent particle breakage to occur. Micro-ball milling under cold condition was more successful at achieving a lower range particle size reduction of soft materials.     

Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: formulation development, <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> evaluation

Lutein is widely used as diet supplement for prevention of age-related macular degeneration. However, the application and efficacy of lutein in food and nutritional products has been hampered due to its poor solubility and low oral bioavailability. This study aimed to develop and evaluate the formulation of oral fast-dissolving film (OFDF) containing lutein nanocrystals for enhanced bioavailability and compliance. Lutein nanocrystals were prepared by anti-solvent precipitation method and then encapsulated into the films by solvent casting method. The formulation of OFDF was optimized by Box-Behnken Design (BBD) as follows: HPMC 2.05% (w/v), PEG 400 1.03% (w/v), Cremophor EL 0.43% (w/v). The obtained films exhibited uniform thickness of 35.64 ± 1.64 μm and drug content of 0.230 ± 0.003 mg/cm² and disintegrated rapidly in 29 ± 8 s. The nanocrystal-loaded films with reconstituted particle size of 377.9 nm showed better folding endurance and faster release rate in vitro than the conventional OFDFs with raw lutein. The microscope images, thermograms, and diffractograms indicated that lutein nanocrystals were highly dispersed into the films. After administrated to SD rats, t _max was decreased from 3 h for oral solution formulation to less than 0.8 h for OFDF formulations, and C _max increased from 150 ng/mL for solution to 350 ng/mL for conventional OFDF or 830 ng/mL for nanocrystal OFDF. The AUC _0-24h of conventional or nanocrystal OFDF was 1.37 or 2.08-fold higher than that of the oral solution, respectively. These results suggested that drug nanocrystal-loaded OFDF can be applied as a promising approach for enhanced bioavailability of poor soluble drugs like lutein.     

Co-Amorphous Combination of Nateglinide-Metformin Hydrochloride for Dissolution Enhancement

The aim of the present work was to prepare a co-amorphous mixture (COAM) of Nateglinide and Metformin hydrochloride to enhance the dissolution rate of poorly soluble Nateglinide. Nateglinide (120 mg) and Metformin hydrochloride (500 mg) COAM, as a dose ratio, were prepared by ball-milling technique. COAMs were characterized for saturation solubility, amorphism and physicochemical interactions (X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR)), SEM, in vitro dissolution, and stability studies. Solubility studies revealed a sevenfold rise in solubility of Nateglinide from 0.061 to 0.423 mg/ml in dose ratio of COAM. Solid-state characterization of COAM suggested amorphization of Nateglinide after 6 h of ball milling. XRPD and DSC studies confirmed amorphism in Nateglinide, whereas FTIR elucidated hydrogen interactions (proton exchange between Nateglinide and Metformin hydrochloride). Interestingly, due to low energy of fusion, Nateglinide was completely amorphized and stabilized by Metformin hydrochloride. Consequently, in vitro drug release showed significant increase in dissolution of Nateglinide in COAM, irrespective of dissolution medium. However, little change was observed in the solubility and dissolution profile of Metformin hydrochloride, revealing small change in its crystallinity. Stability data indicated no traces of devitrification in XRPD of stability sample of COAM, and % drug release remained unaffected at accelerated storage conditions. Amorphism of Nateglinide, proton exchange with Metformin hydrochloride, and stabilization of its amorphous form have been noted in ball-milled COAM of Nateglinide-Metformin hydrochloride, revealing enhanced dissolution of Nateglinide. Thus, COAM of Nateglinide-Metformin hydrochloride system is a promising approach for combination therapy in diabetic patients.     

Stable Co-crystals of Glipizide with Enhanced Dissolution Profiles: Preparation and Characterization

Present study deciphers preparation of co-crystals of lipophilic glipizide by using four different acids, oxalic, malonic, stearic, and benzoic acids, in order to achieve enhanced solubility and dissolution along with stability. All co-crystals were prepared by dissolving drug and individual acids in the ratio of 1:0.5 in acetonitrile at 60–70°C for 15 min, followed by cooling at room temperature for 24 h. FT-IR spectroscopy revealed no molecular interaction between acids and drug as the internal structure and their geometric configurations remain unchanged. Differential scanning calorimetry revealed closer melting points of raw glipizide and its co-crystals, which speculates absence of difference in crystallinity as well as intermolecular bonding of the co-crystals and drug. PXRD further revealed that all the co-crystals were having similar crystallinity as that of raw glipizide except glipizide-malonic acid co-crystals. This minor difference in the relative intensities of some of the diffraction peaks could be attributed to the crystal habit or crystal size modification. SEM revealed difference in the crystal morphology for all the co-crystals. Micromeritic, solubility, dissolution, and stability data revealed that among all the prepared co-crystals, glipizide-stearic acid co-crystals were found superior. Hence, it was concluded that glipizide-stearic acid co-crystals could offer an improved drug design strategy to overcome dissolution and bioavailability related challenges associated with lipophilic glipizide.     

Preparation of Curcumin Loaded Egg Albumin Nanoparticles Using Acetone and Optimization of Desolvation Process

In this study, acetone was used as a desolvating agent to prepare the curcumin-loaded egg albumin nanoparticles. Response surface methodology was employed to analyze the influence of process parameters namely concentration (5–15 %w/v) and pH (5–7) of egg albumin solution on solubility, curcumin loading and entrapment efficiency, nanoparticles yield and particle size. Optimum processing conditions obtained from response surface analysis were found to be the egg albumin solution concentration of 8.85 %w/v and pH of 5. At this optimum condition, the solubility of 33.57 %, curcumin loading of 4.125 %, curcumin entrapment efficiency of 55.23 %, yield of 72.85 % and particles size of 232.6 nm were obtained and these values were related to the values which are predicted using polynomial model equations. Thus, the model equations generated for each response was validated and it can be used to predict the response values at any concentration and pH.     

Controllable biosynthesis of high-purity lead-sulfide (PbS) nanocrystals by regulating the concentration of polyethylene glycol in microbial system

We demonstrated a simple biological method to explore the controllable synthesize of high-purity PbS nanocrystals by regulating the concentration of polyethylene glycol in microbial system. The biogenic H₂S produced via the reduction of sulfate precipitated Pb²⁺ ions as sulfide extracellularly, and the optimal removal rate of Pb²⁺ ions is up to 96.7 % in 2 weeks. The characterization results showed that PbS nanocuboids with a particle size 50 × 50 × 100 nm obtained from Case A with 4 mM polyethylene glycol as a dispersant, and can completely degrade methylene blue from solution within 20 h; PbS nanosheets with a thickness size ca. 10 nm attained from Case B with 12 mM polyethylene glycol, and it can degrade 61.6 % dye within 24 h; PbS nanoparticles with a uniform diameter of ca. 60 nm formed from Case C with 20 mM polyethylene glycol, only degrade 14.1 % dye within 24 h. It is interesting that the factor affecting their catalytic activities is not the specific surface area, but the number of [200] crystal plane. This work not only displayed a simple synthetic method to control the morphology of PbS nanocrystals in microbial system, but also provided an economic and environmentally friendly approach for resourceful treatment and efficient bioremediation of wastewater-containing heavy metal.     

Alpha-chitin nanocrystals prepared from shrimp shells and their specific surface area measurement

Alpha-chitin was isolated from shrimp shells. The chitin was subjected to extensive treatments of acid hydrolysis and mechanical disruption to yield nanocrystals. The goal of this article is to characterize alpha-chitin nanocrystals produced from shrimp shells in regard to crystallite properties and the specific surface area of the chitin nanoparticles. X-ray diffraction data indicate an increase in chitin crystallinity after hydrolysis, as less-ordered chitin domains are digested. Line broadening data were used to measure crystallite size and particle size in the hydrolyzed chitin nanocrystals. Dye adsorption with Congo red was used to measure the specific surface area of the particles, indicating values near 350 m2/g. This value was supported with calculations derived from X-ray crystallite size measurements. Particle surface area measurements were compared with similarly prepared cellulose nanocrystals.     

Effects of grinding processes on enzymatic degradation of wheat straw

The effectiveness of wheat straw fine to ultra-fine grindings at pilot scale was studied. The produced powders were characterised by their particle-size distribution (laser diffraction), crystallinity (WAXS) and enzymatic degradability (Trichoderma reesei enzymatic cocktail). A large range of wheat-straw powders was produced: from coarse (median particle size ∼800 μm) to fine particles (∼50 μm) using sieve-based grindings, then ultra-fine particles ∼20 μm by jet milling and ∼10 μm by ball milling. The wheat straw degradability was enhanced by the decrease of particle size until a limit: ∼100 μm, up to 36% total carbohydrate and 40% glucose hydrolysis yields. Ball milling samples overcame this limit up to 46% total carbohydrate and 72% glucose yields as a consequence of cellulose crystallinity reduction (from 22% to 13%). Ball milling appeared to be an effective pretreatment with similar glucose yield and superior carbohydrate yield compared to steam explosion pretreatment.     

Physicochemical,Thermal, Pasting and Microstructure Properties of Hydroxypropylated Jackfruit Seed Starch Prepared by Etherification with Propylene Oxide

The jackfruit seed starch was subjected to the hydroxypropylation process by using various volumes of propylene oxide in the range of 5–50 ml (HP₅-HP₅₀). It was found that the molecular substitution (MS) increased with the volume of propylene oxide used. The shape of the native starch appeared irregular, round to bell or semi-oval with an average size of 7.66 μm. The modified granules were still intact in granular form without fragmentation. However, the presence of traces of degradation was observed on some starch granules, particularly the treatment of HP₄₀-HP₅₀. No marked differences in the XRD pattern were observed between the native starch and the hydroxypropyl derivatives. However, a decrease in the degree of crystallinity was found as the volume of propylene oxide in the reaction mixture increased. The swelling power and solubility of the hydroxypropylated starches were higher than in the native starch. Progressive increases in swelling power and solubility were observed as the MS increased among the hydroxypropylated starches. The pasting properties revealed that decreases in the pasting temperature, final viscosity and setback was found with increasing MS while the breakdown increased. Hydroxypropylated starches had lower gelatinization parameters (To, Tp, Tc and ?H) compared with the native starch. During refrigerated storage of the starch gel, the native starch showed syneresis from the first cycle while no syneresis was found during seven cycles for the treatment of HP₁₀-HP₅₀.     

Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with <Emphasis Type="Italic">CYP3A5</Emphasis>*3/*3

The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient’s weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.     

Milling plant and soil material in plastic tubes over-estimates carbon and under-estimates nitrogen concentrations

Background and aims

Milling of plant and soil material in plastic tubes, such as microcentrifuge tubes, over-estimates carbon (C) and under-estimates nitrogen (N) concentrations due to the introduction of polypropylene into milled samples, as identified using Fourier-transform infra-red spectroscopy.

Methods and results

This study compares C and N concentrations of roots and soil milled in microcentrifuge tubes versus stainless steel containers, demonstrating that a longer milling time, greater milling intensity, smaller sample size and inclusion of abrasive sample material all increase polypropylene contamination from plastic tubes leading to overestimation of C concentrations by up to 8 % (0.08 g?g^?1).

Conclusions

Erroneous estimations of C and N, and other analytes, must be assumed after milling in plastic tubes and milling methods should be adapted to minimise such error.     

Self-Associated Submicron IgG1 Particles for Pulmonary Delivery: Effects of Non-ionic Surfactants on Size, Shape, Stability, and Aerosol Performance

The ability to produce submicron particles of monoclonal antibodies of different sizes and shapes would enhance their application to pulmonary delivery. Although non-ionic surfactants are widely used as stabilizers in protein formulations, we hypothesized that non-ionic surfactants will affect the shape and size of submicron IgG particles manufactured through precipitation. Submicron particles of IgG1 were produced by a precipitation process which explores the fact that proteins have minimum solubility but maximum precipitation at the isoelectric point. Non-ionic surfactants were used for size and shape control, and as stabilizing agents. Aerosol performance of the antibody nanoparticles was assessed using Andersen Cascade Impactor. Spinhaler® and Handihaler® were used as model DPI devices. SEM micrographs revealed that the shape of the submicron particles was altered by varying the type of surfactant added to the precipitating medium. Particle size as measured by dynamic light scattering was also varied based on the type and concentration of the surfactant. The surfactants were able to stabilize the IgG during the precipitation process. Polyhedral, sponge-like, and spherical nanoparticles demonstrated improved aerosolization properties compared to irregularly shaped (>20 μm) unprocessed particles. Stable antibody submicron particles of different shapes and sizes were prepared. Careful control of the shape of such particles is critical to ensuring optimized lung delivery by dry powder inhalation.     

Changes in pig diet particle size profile and nutrient content during on-farm storage and distribution to the feeders

The present study assessed the effect of silo emptying and feed transport by conveyor systems on particle size and nutrient content of the feed delivered to the pigs. Experiment 1 sampled feed from four feeders along the conveyor system of two barns. Samples were taken immediately after filling the feed silo (Begin) and when the silo was almost empty (End). In Experiment 2, three barns with drag-type conveyors, three with auger-type conveyors and two with spiral-type conveyors were sampled. Along the different conveyors, samples at 10, 20, 50 and 85 m distance from the feed silo were taken from the feeders. In each barn, sampling was repeated for two subsequent batches of feed delivered. In all samples, particle size profile was determined and nutrient content was analysed. In Experiment 2, mineral content was also determined. In Experiment 1, the size of the different particle fractions decreased from Begin to End. An interaction (p < 0.05) between sampling time and conveyor type was detected for the 10% smallest particles. In Experiment 2, an effect of sampling time on the 10% largest particles was detected (p < 0.05). The effect of sampling time on several nutrients was observed in Experiments 1 and 2, but the affected nutrients differed between both experiments. Results implied that it was mainly emptying of the silo that affected mash particle size profile and nutrient content. The potential impact of these changes on pig performance requires further investigation.     

Novel Dexamethasone-Loaded Nanomicelles for the Intermediate and Posterior Segment Uveitis

Development and characterization of dexamethasone (DEX)-encapsulated polymeric nanomicelles have been reported. A low molecular weight di-block copolymer was synthesized and characterized for its structure, molecular weights, critical micelle concentration (CMC), and cytotoxicity in ocular cells. In order to delineate the effects of drug–polymer interactions on drug solubilization in micelle core, a response surface methodology was generated with the help of SAS 9.02 (exploratory model). The method for preparing micelle was modified based on the results obtained from exploratory model. The formulation was optimized by response surface methodology (optimization model) to achieve DEX solubility of above 1 mg/mL. The optimized formulation was characterized for DEX solubility, nanomicelle size, polydispersity index, surface morphology, in vitro transport across conjunctival cell line, and ex vivo transport across excised rabbit sclera. Nanomicelles exhibited average sizes in range of 25–30 nm with unimodel size distribution and low polydispersity of 0.125. Nanomicelles increased DEX permeability by 2 times across conjunctival cell line and by 2.5 times across the excised rabbit sclera as compared to DEX suspension. A design of experiment (DOE) strategy was successfully applied to understand the effects of drug–polymer interaction on drug solubility. DOE was also employed to achieve optimal formulation with high DEX solubility. Nanomicellar formulation significantly enhanced DEX permeability across the excised rabbit sclera. Therefore, nanomicellar formulation may provide therapeutic levels in the back of the eye following topical administration.     

Feasibility of Manufacturing Cellulose Nanocrystals from the Solid Residues of Second-Generation Ethanol Production from Sugarcane Bagasse

The reuse of the solid residues generated in the production of second-generation (2G) ethanol to obtain high-value products is a potential strategy for improving the economic and environmental viability of the overall process. This study evaluated the feasibility of using the residual solids remaining after the enzymatic hydrolysis of sugarcane bagasse for the production of cellulose nanocrystals (CNC), a valuable bionanomaterial. To this end, sugarcane bagasse subjected to steam explosion (SEB) or liquid hot water (LHWB) pretreatment was hydrolysed using different loadings of a commercial cellulase cocktail. Samples of SEB and LHWB were hydrolysed enzymatically, resulting in glucose releases close to 40 g/L, which would be suitable for producing 2G ethanol by microbial fermentation. The solid residues after the enzymatic hydrolysis step presented cellulose contents of up to 54 %, indicating that a significant amount of recalcitrant crystalline cellulose remained available for subsequent use. These solid residues were purified and submitted to acid hydrolysis, resulting in the successful formation of CNC with crystallinity close to 80 %, lengths of 193–246 nm and diameters of 14–18 nm. The CNC produced presented morphology, dimensions, physical-chemical characteristics, thermal stability and crystallinity within the ranges reported for this type of material. Moreover, the enzyme loading or the type of hydrothermal pretreatment process employed here showed no significant effects on the CNC obtained, indicating that these variables could be flexibly adjusted according to specific interests.     

Theoretical investigations on the structure, density, thermodynamic and performance properties of amino-, methyl-, nitroso- and nitrotriazolones

We have studied herein the effect of position and the number of -NO, -NO₂, -NH₂ and -CH₃ groups on the structure, stability, impact sensitivity, density, thermodynamic and detonation properties of triazolones by performing density functional theory calculations at the B3LYP/aug-cc-pVDZ level. The optimized structures, vibrational frequencies and thermodynamic values for triazolones have been obtained in their ground state. Kamlet-Jacob equations were used to calculate the detonation velocity and detonation pressure of model compounds. The detonation properties of NNTO (D 8.75 to 9.10 km/s, P 34.0 to 37.57 GPa), DNTO (D 8.80 to 9.05 km/s, P 35.55 to 38.27 GPa), ADNTO (D 9.01 to 9.42 km/s and P 37.81 to 41.10 GPa) and ANNTO (D 8.58 to 9.0 km/s, P 30.81 to 36.25 GPa) are compared with those of 1,3,5-trinitro-1,3,5-triazine (RDX) (D 8.75 km/s, P 34.70 Gpa) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) (D 8.96 km/s, P 35.96 GPa). The designed compounds satisfy the criteria of high energy materials.