Capsule Contents Research Articles

Influence of the quality of capsule shell on the non-invasive monitoring of medicines using Terizidone as an example

The aim of this study is to investigate the influence of hard capsule shells on the possibility of non-invasive monitoring and authentication of medicines presented in capsules dosage form. It is shown that the NIR measurements followed by the chemometric analysis, reflects all macro-components of the analyzed samples, which are the PVC blister, the capsule shell, and the capsule contents. The special variable selection procedure, based on the pure spectra of all components, makes it possible to develop a model that is insensitive to small variations of the capsule shell. The shrinkage of spectral region can greatly affect the results of the classification.Consequently, in case we are interested in the whole remedy, capsules with deviations in shell properties should be rejected as the substandard ones. If we are only interested in the quality of capsules’ content, the developed model is effective and applicable in the routine testing. The final model helps to understand and demonstrate the reason for the rejection of substandard samples authentication. It also gives a practical signal to the manufacturer to pay attention to the quality of the capsule shells.

Economical irregular silica as an effective dispersive solid-phase extraction sorbent for the quantification of calcitriol in soft capsules

Calcitriol is an active product of vitamin D produced by the liver and kidney hydroxylase metabolism with strong physiological activity. It is the preferred form of medicine for patients with insufficient bone mineralization due to chronic kidney disease. Calcitriol soft capsule is one of the common preparation forms, the main drug content of which is very low (1.55 μg g−1), and the pharmaceutical excipients interfere greatly, especially the oily matrix medium-chain triglycerides. Therefore, removing the interference of oily matrix is ​​the main challenge in the content determination. At present, the commonly used sample purification method for the determination of calcitriol in soft capsules is liquid-liquid extraction, but it usually consumes a lot of toxic organic solvents and it is costly. The adoption of SPE purification method, on the one hand, requires specific experimental equipment, and on the other hand, the organic solvent used in the experiment may cause the dissolution of SPE column tube materials, which will interfere with the subsequent detection. Herein, in order to achieve a cost-effective and reliable determination of calcitriol soft capsule content, we developed a dispersive solid-phase (DSPE) extraction method that directly uses irregular silica as sorbent, which is followed by high-performance liquid chromatography equipped with a UV detector(HPLC-UV)analysis. Selective retention of calcitriol is achieved by the polar interaction between calcitriol and silica, what’s more, sufficient contact between washing solvent and sorbent can be guaranteed. Therefore, after pretreatment with DSPE, the interference of oily matrix on detection can be mostly removed and then improve the accuracy of the method compared to the SPE method. Under the optimal conditions of DSPE, calcitriol showed a good linear relationship in the range of 0.15−2.99 μg g−1, the R2 was 0.997. Satisfactory recoveries ranging from 101.1%–102.0% for calcitriol were achieved in the oily matrix at the levels of 0.75, 1.50 and 2.24 μg g−1. And the intra-day and inter-day RSD were less than 2.5 % and 3.2 %. Meanwhile, the LOD and LOQ of calcitriol was 0.01 μg g−1 and 0.02 μg g−1, which is in full compliance with the regulatory level fixed by the EU, China or other countries. This method was further verified to determine the content of calcitriol in commercial calcitriol soft capsules and the recoveries of three batches of products was 86.2 %–94.4 %. Based on these characteristics, the proposed method makes it possible to determine the low content of weakly polar drugs in the oily matrix in a simple, low-cost and reliable way.

Essential oil-loaded nanocapsules and their application on PBAT biodegradable films

Active biodegradable packaging is an important area. The shelf life increased in packaged food, minimizing the disposal of solid waste. In this work, different chitosan nanocapsules (CN-EO) content (2, 5, and 8 wt%) loaded with cinnamon essential oil (EO) were prepared and used as active agents in poly(butylene adipate-co-terephthalate) films. The prepared samples were characterized by chemical, physical–chemical, mechanical, and biological properties. The CN-EO presented monodispersed sizes from 20 to 100 nm and spherical shape. The nanocapsules showed biological activity due to the synergistic antibacterial efficiency of chitosan and essential oil, and when applied to the films, it promoted inhibition against E. coli. The highest CN-EO (8 wt%) improved the films' mechanical properties, which can be associated with strong interactions between the materials and the increase in PBAT crystallinity. The changes in films' crystallinity and capsules content influenced the oil release and, consequently, antimicrobial properties. The films showed good potential for food packaging application, being an alternative to conventional packaging's environmental problems.

POS-181 RARE INVOLVEMENT OF THYROID GLAND WITH ASPERGILLOSIS IN RENAL TRANSPLANT RECEPIENT

Aspergillosis is an infection caused by saprophytic fungi normally found in soil and decaying vegetation. Although there are more than 1000 Aspergillus species, only Aspergillus niger, A. fumigatus and A. flavus are pathogenic. Though disseminated invasive aspergillosis is seen in 20 % cases, but reports of aspergillosis that has disseminated to the thyroid gland, presenting as vocal cord palsy and treated in renal transplant patients, as in this case, are extremely rare. We present a case of 47 years old male who underwent live related kidney transplantation. 3 months post-transplant, he had acute cellular rejection which was treated with pulse methyl prednisolone and anti-thymocyte globulin. He also had recent admission for Klebsiella pneumonia related consolidation which was treated with antibiotics. Though the sputum also showed few fungal hyphae but as he was responding to antibiotics, no antifungal was added. In this admission he was admitted for hoarseness of voice which was diagnosed due to left vocal cord palsy on laryngoscopic examination. MRI neck revealed hyperintense lesion most probably colloidal nodule on left mid and lower pole of thyroid on T2 imaging. FNAC yielded fungal hyphae with regular septation and acute branching, morphologically consistent with aspergillus. Galactomannan assay was positive. Thyroid profile was normal. Sputum for fungal stain also yielded hyphae of filamentous fungi. He was started on oral voriconazole and was serially monitored with USG neck and galactomannan assay. Fungal infections of the thyroid are extremely uncommon. A rich blood and lymphatic supply, well developed capsule and high iodine content of the gland are various mechanism of resistance to infection. Most of thyroid lesions of invasive Aspergillosis are described as focal abscesses, patchy haemorrhagic lesions due to vascular invasion or diffuse necrotizing thyroiditis. In patients with thyroid Aspergillosis, local inflammation and direct tissue destruction caused by fungi can cause thyroid hormones to leak into the bloodstream, sometimes leading to thyrotoxicosis. Though in our case patient had normal thyroid profile and he was asymptomatic apart from hoarseness of voice.The galactomannan assay which detects galactomannan antigen, which is component of Aspergillus cell wall, can detect aspergillosis before symptoms appear, but sensitivity and specificity in solid organ transplant patients are lower than in haematological patients. Though surgical options can be tried whenever the lesion is accessible like in this case but voriconazole is the most effective drug for disseminated and invasive Aspergillosis. It inhibits the activity of cytochrome P450-3A4; that’s why the tacrolimus dose should be reduced to prevent nephrotoxicity. Due to various innate resistance mechanism, fungal infections of the thyroid are extremely uncommon. Aspergillosis in our case presented as change in voice. It was diagnosed by FNAC of nodular lesion of thyroid gland. Though surgical excision can be tried but as in this case, it can be treated with voriconazole with serial galactomannan and ultrasonographic monitoring.

Acetaminophen and tramadol hydrochloride-loaded soft gelatin capsule: preparation, dissolution and pharmacokinetics in beagle dogs

The objective of this study was to develop a novel acetaminophen and tramadol hydrochloride-loaded soft capsule (ATSC) with enhanced bioavailability of tramadol. The ATSC was manufactured in a pilot-scale batch size with the capsule contents composed of tramadol, acetaminophen, PEG 400 and Capmul MCM at a weight ratio of 37.5:325:177.5:30. Moreover, its dissolution, stability and pharmacokinetics in beagle dogs were carried out compared to commercial tablet. The dissolved amounts of acetaminophen from the ATSC and commercial tablet were not significantly different. However, compared to the latter, the former had significantly higher dissolution rate of tramadol at the initial times. In beagle dogs, the ATSC provided no significant difference in plasma concentrations and AUC of acetaminophen than did the commercial tablet; however, it significantly improved those of tramadol compared to the other, indicating the enhanced oral bioavailability of tramadol. Compared to the commercial tablet, the ATSC had a larger AUC value for tramadol (55.27 ± 11.06 vs. 92.62 ± 21.52 h·ng/ml). In the accelerated long-term stability, the ATSC offered higher than 96% drug content of acetaminophen and tramadol, suggesting that it was stable for at least six months. Therefore, this ATSC would be a recommendable candidate with enhanced oral bioavailability and excellent stability.

Effect of epoxy resin healing agent viscosity on the self-healing performance of capsules reinforced polymer composite

The structural integrity of micro and nano cracked polymer composites can be re-established without human intervention by employing biologically inspired capsule based self-healing system into the base material. In the present study, in order to evaluate the influence of core materials viscosity on the self-healing performance, two types of epoxy resins (LY556, CY230) of respective viscosities 10-12 Pa.s, 1.3-2 Pa.s and amine hardener (HY951) of viscosity 0.01–0.02 Pa.s were chosen and encapsulated in a thermoplastic poly methylmethacrylate (PMMA) shell. The mean capsule size of the developed LY556 epoxy,CY230 epoxy microcapsules and HY951 hardener microcapsules were measured as 61.58 µm, 67.64 µm and 63.31 µm respectively. Influence of core to shell(c/s) ratio on the preparation of epoxy capsules was investigated and 1:1 c/s ratio, 2:1 c/s ratios were recommended as an ideal ratios to prepare LY556, CY230 epoxy capsules respectively. Fourier Transform Infrared (FTIR), Nuclear magnetic resonance (NMR) and thermogravimetric(TGA) analysis were conducted. Tensile strength, fracture toughness and self-healing performance of the (LY556 + HY951) capsules, (CY230 + HY951) capsules reinforced epoxy composites were investigated. It was noticed that the tensile strength decreases and the fracture toughness increases with the increase in capsules concentration from 0wt% to 10wt%. In both the cases, it was found that the healing efficiency increased with the increase in capsules content. For both (LY556 + HY951) capsules reinforced, (CY230 + HY951) capsules reinforced epoxy composites an optimum capsules concentration was found to be at 7.5wt% and the respective measured healing efficiencies were noted as 66% and 72%.

Construction and Study of the Application of Novel Norfloxacin Fluorescent Probes

In this experiment, a fluorescent probe of tricyanohydrofuran-norfloxacin was successfully constructed. Fluorescence spectrophotometer was used to detect the fluorescence intensity of the system under the condition of the excitation wavelength was 362nm and the emission wavelength was 448nm. The optimal experimental conditions were optimized (the concentration of the complex, the amount of norfloxacin, pH, temperature and reaction time). The optimal concentration of the complex in the system is in the range of 1.0×10−3-3.5×10−4 mol·L−1, the dosage was 0.6mL, and optimal dosage of norfloxacin was 3.0 ml, the optimum pH of the system was 5.5, under this condition the fluorescence intensity of the system was the strongest. At the same time, the intramolecular charge transfer reaction mechanism of fluorescent probe was studied. And testing the content of norfloxacin capsules, the results were satisfactory. A new testing method of norfloxacin content successfully created.

Moisture content and mechanical properties reduction of hard capsules upon prolong drying process

Drying is a traditional preservation method to control the properties and quality of pharmaceutical product such as hard capsule. In this study, carrageenan and nanocellulose (NC) solution were mixed with crosslinker and toughening agents in the formulation solution and dipped for hard capsule formation. The dipping bar was dried at different drying times from 40-60 minutes in an oven. The properties of carrageenan hard capsule were compared with commercial hard capsule materials which were gelatine and hydroxypropyl methylcellulose (HPMC). Prolong drying time decreased the moisture content and hydroxyl group absorbance of carrageenan hard capsule up to 20 % and 2%, respectively. The mechanical properties of the hard capsule sample reduced about 19.2 % due to reduction of intermolecular interaction between carrageenan, crosslinker and NC. Increment drying time leads to tissue shrinkage in carrageenan hard capsule thus collapse the biocomposite structure and mechanical properties. Gelatine and HPMC hard capsules had lower moisture content and higher mechanical strength and thermal properties as compared to carrageenan hard capsule. As the drying time increase, case hardening phenomena collapses the structure and change the structure chain in the biocomposite.

Estimation of heterosis and pattern of inheritance for elite economic yield traits in opium poppy (<em>Papaver somniferum</em> L.)

A line × tester analysis was conducted to assets the heterosis, heterobeltiosis and economic heterosis of sixty F1’s by crossing 12 lines/females and 5 testers/males of diverse parents for fourteen viable economical traits in Papaver somniferum L. The analysis of variance concluded that parents vs hybrids contrast were recorded only 50% significant for the characters and rest non-significant for the traits like days to flowering (50%), no. of leaves/plant, pedicel length, no. of capsule/plant, Seed yield, dry husk capsule and codeine alkaloid content (%) indicated, existence of plentiful variability among parents and crosses for all the characters studied. The investigational result revealed that hybrids L10×T2, L10×T5, L12×T3 and L12×T4 exhibited the best heterosis over better as well as economic parent both for more than one traits, namely- no. of capsule, capsule index, seed yield (g/plant), dry husk yield (g/plant), morphine, codeine, thebaine, papervine and nosacapine alkaloid content (%) in desirable direction. Therefore, these promising crosses can be recommended for exploitation of heterosis to obtain appropriate segregants for crop improvement program in opium poppy.

Dissolution time and shelf life quality of Ficus deltoidea powder and granule

Lyophilized from plants extract is a process to prolong the amounts of phytochemicals in a solid form. The bioactive compound in Ficus deltoidea (FD), which is isovitexin should be stable and bioavailable during the downstream processing such as drying process to achieve its optimum health benefits. Therefore, this study focuses on the impact of lyophilizing methods such as spray drying followed by a granulator method to determine the stability of the bioactive compound in FD during drying and storage. After the powdered produce, it will test on the model of human digestion (dissolution study) either the amounts of phytochemicals remain stable. Finally, shelf-life quality analysis and the dissolution rate (capsule size 0 and 1) were carried out. The results obtained show the methods employed in this study can be used for the analysis of quality content and dissolution tests of FD capsules. For FD in the shelf-life quality study, parameters for appearance and Total Yeast Microbial Count (TYMC) showed no significant difference after 3 months. For pH, the slight decrease in pH level will increase the number of Total Aerobic Microbial Count (TAMC) in powder form. Compared to granule form, the pH level more consistent and the number of TAMC also in a control condition. The dissolution of capsules containing powder and granulated of FD showed a high percentage of bioactive compound released into the dissolution medium, although the bioactive compound content of herbal products (capsule size 1) was found to be half that of capsules size 0. Through observation for both capsules size content of FD, the maximum dissolution was achieved after 100 min.

Nondestructive qualitative and quantitative analysis of Yaobitong capsule using near-infrared spectroscopy in tandem with chemometrics

The purpose of the study is to present a nondestructive qualitative and quantitative approach of hard-shell capsule using near-infrared (NIR) spectroscopy combined with chemometrics. The Yaobitong capsule (YBTC) was used for demonstration of the proposed approach and the NIR spectra were collected using a handheld fiber probe (FP) without the damage of capsule shell. By comparing the differences and similarities of the NIR spectra of capsule shells, contents and intact capsules, a preliminary conclusion can be drawn that the NIR spectra contained the information of the contents. Characteristic variables were selected by competitive adaptive weighted resampling (CARS) method, and least squares support vector machine (LSSVM) method based on particle swarm optimization (PSO) algorithm was applied to the construction of quantitative models. The relative standard error of prediction (RSEP) values of five saponins including notoginsenoside R1, ginsenoside Rg1, Re, Rb1, and Rd were 3.240%, 5.468%, 5.303%, 5.043%, and 3.745%, respectively. In addition, for qualitative model, three different types of adulterated capsules were designed. The model established by data driven version of soft independent modeling of class analogy (DD-SIMCA) demonstrated a satisfactory result that all adulterated capsules were identified accurately after an appropriate number of principal components (PCs) were chosen. The results indicated that although the NIR spectra collection was affected by capsule shell, sufficient content information can be obtained for quantitative and qualitative analysis after combining with chemometrics. It further proved that acquired NIR spectra do contain the effective component information of the capsule. This study provided a reference for the rapid nondestructive quality analysis of traditional Chinese medicine (TCM) capsule without damaging capsule shell.

HPMC Capsules for Moisture Sensitive and Hygroscopic Products

<i>Background</i>: Moisture content varies in capsules made from different materials. Gelatin capsules contain 13-16% moisture. HPMC (Hydroxypropyl methyl cellulose or Hypromellose) capsules may contain moisture 2- 8%. Usual HPMC capsules have inherently low moisture content which allows for the encapsulation of ingredients that are sensitive to moisture and are hygroscopic in nature. This has greatly broadened the scope of capsules in drug delivery. Moisture content of HPMC capsules can be reduced as low as 2%. HPMC capsules lower moisture content is better for moisture sensitive and hygroscopic products. <i>Objective</i>: Low moisture content of HPMC capsules help to improve stability of moisture sensitive active pharmaceutical and active nutraceutical active ingredients. This is illustrated with examples. Different properties of HPMC capsules helps targeted delivery. It offers some special advantages for nutraceutical products. It also helps to improve physical stability of capsules. Liquid filled hard capsules provide many options and are commonly used for nutraceutical products.

1303. Characterization of Isavuconazole Serum Concentrations with Various Administration Routes in a Hospitalized Cohort

BackgroundPatients with invasive fungal infections are often critically ill and immunosuppressed with multiple comorbidities that may impact drug absorption and exposure. This study sought to characterize isavuconazole serum concentrations (ISCs) in a cohort of real-world hospitalized patients when administered by intravenous solution (IV), enteral as intact capsules, or tube as opened capsule contents.MethodsThis retrospective cohort analysis included all hospitalized patients who received isavuconazole as prophylaxis or treatment between September 2017 and September 2018 and had therapeutic drug monitoring performed. For patients receiving isavuconazole by tube, the capsules were opened and contents were diluted with 10-30 mL of sterile water. Administration was per package insert for intact capsules and IV solution. ISCs were obtained as part of routine care and were quantified by high-performance liquid chromatography. An appropriate trough was defined as within 4 hours of the next scheduled dose. Currently, there is a lack of correlation between isavuconazole exposure and efficacy or toxicity; thus, ISCs were compared between administration routes.Results93 ISCs were obtained during 65 encounters from 55 unique patients. The majority of patients were post-transplant (69.1%) and death occurred during 12 (18.5%) encounters. ISCs based on different characteristics of the cohort are shown in Table 1. All ISC assessments were detectable, median 2.3 mg/dL (Q1: 1.5 mg/dL, Q3: 3.3 mg/dL). Administration via tube achieved similar ISCs compared with IV therapy (1.6 mg/dL vs. 1.9 mg/dL, respectively). However, administration of intact capsules resulted in higher median ISCs, 3 mg/dL (Q1: 1.9 mg/dL, Q3: 4.1 mg/dL). All 14 patients with administration via tube were post-transplant, which was not shown to have a significant impact on ISCs (median, transplant 2.2 mg/dL vs. non-transplant 2.7 mg/dL).Table 1. Characterization of Isavuconazole Concentrations ConclusionISCs were detectable in all patients regardless of transplant status or location at the time of assessment. Administration of isavuconazole via an enteral feeding tube achieved comparable serum concentrations compared with FDA-approved routes of administration and may represent an important alternative for select patients.Disclosures All Authors: No reported disclosures

ROLE OF ULTRASONOGRAPHY IN DIAGNOSIS OF SPINAL STENOSIS WITH LUMBAR OSTEOCHONDROSIS

Diagnostic visual examinations for patients with any type of spinal stenosis include either magnetic resonance imaging or computed tomography with myelogram, sometimes both tests are prescribed to patients. Ultrasound is usually most effective for tissues with a high content of collagen, i.e. tendons, ligaments, joint capsules and fascia. In osteochondrosis, spinal ultrasonography is used to determine whether a back pain is the result of cracks or a herniated disc. To evaluate the possibilities of ultrasound in diagnosis of lumbar spine stenosis, an analysis of its results in 48 patients aged 41−57 years. Forty five of them were diagnosed with intervertebral disc herniation, 3 with protrusion of various localization and hypertrophy of the yellow ligament. All the patients underwent radiography, magnetic resonance or computed tomography, as well as ultrasound. In 24 patients the laminectomy was performed in 31 discs. In 21 cases, the hernia was paramedian, in 17 it was − median and in 14 this was circular. Laminectomies were performed much more frequently due to median and circular hernias. The slightest deformation of spinal canal is observed in the posterolateral localization of hernia or protrusion. In thin individuals, ultrasound images of the spinal canal elements were excellent, in those with moderate weight they were slightly inferior to magnetic resonance imaging. In three cases of spinal canal stenosis in obese patients who underwent laminectomy, the results of ultrasonography were unsatisfactory and the decision for surgery was made only on the basis of magnetic resonance imaging. It is concluded that ultrasound is a very informative way of assessing the degree of lumbar spine stenosis resulted from degenerative changes in intervertebral discs. Key words: ultrasonography, spinal canal stenosis, lumbar osteochondrosis, lumbar intervertebral discs.

Quantitative Analysis of Emtricitabine in Dosage Forms Using Green RP-HPTLC and Routine NP-HPTLC Methods-A Contrast of Validation Parameters.

In this research, an antiviral drug emtricitabine (ECT) was quantified using the validated green reversed-phase high-performance thin-layer chromatography (RP-HPTLC) and routine normal-phase HPTLC (NP-HPTLC) methods in the marketed oral solutions and capsules. Green RP-HPTLC-densitometry quantification was performed using the acetone/water (70:30, v/v) solvent system as the mobile phase. Routine NP-HPTLC-densitometry quantification was performed using the chloroform/methanol (85:15, v/v) solvent system as the mobile phase. The detection was performed at λmax—285 nm for both of the methods. Both densitometry methods were validated for different parameters. Most of the validation parameters including linearity, precision, accuracy, detection, and quantification limits for the green densitometry method were found to be superior compared to the routine densitometry technique. The ECT contents of commercial oral solution and commercial capsules were found to be 100.85 and 98.27%, respectively, using the green densitometry technique. The ECT contents of oral solutions and capsules were 97.16 and 95.54%, respectively, using the routine densitometry technique. Accordingly, the green densitometry technique was found to be better than the routine densitometry technique for ECT assays. Thus, the green densitometry technique can be successfully applied for the quantitation of ECT in the marketed formulations.

Encapsulation of fragrances in micron-size silk fibroin carriers via coaxial electrohydrodynamic techniques

Herein, we present the successful application of coaxial electrostatic atomization technology for encapsulation of volatile fragrances in silk fibroin (SF) matrices with l-menthol (MenOH) as a model compound. The fragrance-loaded core-shell fibers and capsules of a mean diameter of 1–2 μm were fabricated on the same apparatus, and their structural characteristics could be tuned by changing the ratio of a component in core and shell and matching with process parameters. By decreasing the concentration of the core solution, the loading capacity (LC) of electrospun fibers was up to 12 wt% with an encapsulation efficiency (EE) of ~46%. The fragrance content of capsules was 4% since a limited amount of MenOH incorporated in the case of electrospray. Impregnation with alcohol was effective in hardening SF shell and thus significantly decreasing the diffusion of aroma molecules. The fragrance release profile and rate of the composites were controlled by the degree of crystallinity of SF matrix and the shell thickness. Also, the fragrance microcapsules could be directly deposited on the fabric surface during electrospray and showed good washing durability.

Polydopamine-Coated Paraffin Microcapsules as a Multifunctional Filler Enhancing Thermal and Mechanical Performance of a Flexible Epoxy Resin

This work focuses on flexible epoxy (EP) composites containing various amounts of neat and polydopamine (PDA)-coated paraffin microcapsules as a phase change material (PCM), which have potential applications as adhesives or flexible interfaces with thermal management capability for electronics or other high-value-added fields. After PDA modification, the surface of PDA-coated capsules (MC-PDA) becomes rough with a globular appearance, and the PDA layer enhances the adhesion with the surrounding epoxy matrix, as shown by scanning electron microscopy. PDA deposition parameters have been successfully tuned to obtain a PDA layer with a thickness of 53 ± 8 nm, and the total PDA mass in MC-PDA is only 2.2 wt %, considerably lower than previous results. This accounts for the fact that the phase change enthalpy of MC-PDA is only marginally lower than that of neat microcapsules (MC), being 221.1 J/g and 227.7 J/g, respectively. Differential scanning calorimetry shows that the phase change enthalpy of the prepared composites increases with the capsule content (up to 87.8 J/g) and that the enthalpy of the composites containing MC-PDA is comparable to that of the composites with MC. Dynamic mechanical analysis evidences a decreasing step in the storage modulus of all composites at the glass transition of the EP phase, but no additional signals are detected at the PCM melting. PCM addition positively contributes to the storage modulus both at room temperature and above Tg of the EP phase, and this effect is more evident for composites containing MC-PDA. As the capsule content increases, the mechanical properties of the host EP matrix also increase in terms of elastic modulus (up to +195%), tensile strength (up to +42%), Shore D hardness (up to +36%), and creep compliance (down to −54% at 60 min). These effects are more evident for composites containing MC-PDA due to the enhanced interfacial adhesion.

Self-healing of asphalt mastic using capsules containing waste oils

Several capsules were prepared using two different waste oils (vegetable oils and mineral oils), five different oil/water ratios, and four different amounts of sodium alginate as a polymer matrix. Capsules with waste oils were characterized by physical, thermal, and mechanical properties to define the more effective capsule for asphalt self-healing purposes. The capsules were added in ratios of 0.25%, 0.50%, 0.75%, and 1.0% by total weight of mastic. The crack-healing efficiency of the optimum capsules was evaluated at two different curing temperatures (25 °C and 40 °C) on asphalt mastic samples using three-point bending tests. The main results proved that capsules could survive the mixing and compacting processes and releasing the encapsulated waste oils inside them by the action of mechanical loads. 100 ml water, 500 ml waste oil, and 17.5 gr sodium alginate were found to be the optimum capsule content for both types of oils. An increased rate of water/oil resulted in decreased free compressive strength. It was further detected that the self-healing levels of asphalt mastic samples with capsules demonstrated 80% higher healing levels compared to samples without capsules and the level of self-healing depended on the ratio of capsules added into the mixtures and the curing temperature applied.

Structure elucidation of a PDE5 inhibitor detected as an illegal adulteration in a libido-boosting dietary supplement

ABSTRACT A compound with potent inhibitory activity for phosphodiesterase type 5 (PDE5) was identified as an illegal adulteration in a libido-boosting dietary supplement being sold at a store in Tokyo. This compound was identified as 5,6-diethyl-2-{5-[(4-methylpiperazin-1-yl)sulphonyl]-2-propoxyphenyl}pyrimidin-4(3H)-one using liquid chromatography-diode array detector (LC-DAD), liquid chromatography-tandem mass spectrometer (LC-MS), LC-HRMS, nuclear magnetic resonance (NMR), and X-ray crystallography. The IC50 value of the inhibitory activity for PDE5A1 (one of the PDE5 isoforms) was 2.0 nM (sildenafil IC50 value was 6.3 nM). This compound was previously synthesised as a PDE5 inhibitor by Shanghai Institute of Materia Medica. The dietary supplement contained 85 mg of this compound in a capsule, which was about 26% of the capsule content (320 mg).

Diversity of mucoid to non-mucoid switch among carbapenemase-producing Klebsiella pneumoniae

BackgroundKlebsiella pneumoniae is a leading cause of intractable hospital-acquired multidrug-resistant infections and carbapenemase-producing K. pneumoniae (CPKp) are particularly feared. Most of the clinical isolates produce capsule as a major virulence factor. Recombination events at the capsule locus are frequent and responsible for capsule diversity within Klebsiella spp. Capsule diversity may also occur within clonal bacterial populations generating differences in colony aspect. However, little is known about this phenomenon of phenotypic variation in CPKp and its consequences.ResultsHere, we explored the genetic causes of in vitro switching from capsulated, mucoid to non-mucoid, non-capsulated phenotype in eight clinical CPKp isolates. We compared capsulated, mucoid colony variants with one of their non-capsulated, non-mucoid isogenic variant. The two colony variants were distinguished by their appearance on solid medium. Whole genome comparison was used to infer mutations causing phenotypic differences. The frequency of phenotypic switch was strain-dependent and increased along with colony development on plate. We observed, for 72 non-capsulated variants that the loss of the mucoid phenotype correlates with capsule deficiency and diverse genetic events, including transposition of insertion sequences or point mutations, affecting genes belonging to the capsule operon. Reduced or loss of capsular production was associated with various in vitro phenotypic changes, affecting susceptibility to carbapenem but not to colistin, in vitro biofilm formation and autoaggregation.ConclusionsThe different impact of the phenotypic variation among the eight isolates in terms of capsule content, biofilm production and carbapenem susceptibility suggested heterogeneous selective advantage for capsular loss according to the strain and the mutation. Based on our results, we believe that attention should be paid in the phenotypic characterization of CPKp clinical isolates, particularly of traits related to virulence and carbapenem resistance.