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Adeno-associated virus (AAV) vectors are widely used to deliver therapeutic transgenes due to their superior safety, relatively low immunogenicity, and ability to target diverse tissues. AAV gene therapy products are typically formulated as frozen liquid and stored below − 60 °C, and therefore are subjected to multiple freeze/thaw cycles during manufacturing and administration. Recent studies have shown that genome DNA leakage could be induced by freeze/thaw stress. DNA leakage from AAV capsids has been reported to potentially impact product stability, induce immune responses, and compromise product efficacy. Thus, further characterization to improve the understanding of genome DNA leakage is necessary for mitigating the risks associated with genome DNA leakage during AAV product development. In this work, we developed an optimized size-exclusion chromatography (SEC) method for quantifying the leakage of genome DNA across multiple different AAV serotypes and demonstrated satisfactory assay performance in sensitivity, precision, and linearity. Furthermore, we showed that this method could also be applied to quantifying additional quality attributes of AAV, including the percentage of full capsids and quantification of AAV dimers. By using this optimized SEC method, we demonstrated that significantly increased free DNA was observed with increasing freeze/thaw cycles or at a temperature approaching the onset temperature for genome DNA ejection, which was effectively mitigated by the addition of 1.5% w/v sucrose in the AAV formulation. Thus, this optimized SEC method can serve as an invaluable tool for AAV formulation, product, and process development in ensuring the quality and stability of AAV gene therapy products. [ABSTRACT FROM AUTHOR]

Chlorpyrifos is among the most widely sold organophosphates in the agriculture sector worldwide. Static bioassays were performed in the laboratory to compare the acute toxicity between the technical grade (94% a.i.) and commercial formulation (20% EC) of chlorpyrifos to four freshwater organisms: the crustacean zooplankton Cyclops viridis, the oligochaete worm Branchiura sowerbyi, the gastropod Pila globosa, and tadpole larvae of Duttaphrynus melanostictus. The recovery of actual chlorpyrifos concentrations in water after 2 h of exposure to the nominal concentrations ranged from 82.98% to 88.56%. The commercial formulation (F) of chlorpyrifos was found to be 1.94 to 2.76 times more toxic than the technical grade (T). Based on 96 h LC50 values of T and F chlorpyrifos, C. viridis was found to be most sensitive (0.56 and 0.25 μg/L) and P. globosa as most tolerant (1482 and 536 μg/L) to chlorpyrifos. Changes in LC50 values of both T and F chlorpyrifos were noted in respect of exposure hours for the three aquatic invertebrates and the tadpole larvae of the toad. In conclusion, the acute toxicity of chlorpyrifos to some non-target freshwater organisms differs between technical grade and commercial formulations. [ABSTRACT FROM AUTHOR]

Niacinamide, an active form of vitamin B3, is recognised for its significant dermal benefits including skin brightening, anti-ageing properties and the protection of the skin barrier. Its widespread incorporation into cosmetic products, ranging from cleansers to serums, is attributed to its safety profile and proven efficacy. Recently, topical niacinamide has also been explored for other pharmaceutical applications, including skin cancers. Therefore, a fundamental understanding of the skin permeation behaviour of niacinamide becomes crucial for formulation design. Given the paucity of a comprehensive review on this aspect, we provide insights into the mechanisms of action of topically applied niacinamide and share the current strategies used to enhance its skin permeation. This review also consolidates clinical evidence of topical niacinamide for its cosmeceutical uses and as treatment for some skin disorders, including dermatitis, acne vulgaris and actinic keratosis. We also emphasise the current exploration and perspectives on the delivery designs of topical niacinamide, highlighting the potential development of formulations focused on enhancing skin permeation, particularly for clinical benefits. [ABSTRACT FROM AUTHOR]

Efficient delivery of low water soluble paclitaxel (PTX) through the use of human serum albumin (HSA) as suitable carriers to targeted site with reduced toxicities and improved pharmaceutical attributes remains challengeable and still required deep investigation. Herein, PTX-HSA NPs were synthesized by emulsion solvent evaporation method using high-pressure homogenization technique. The impact of drug and HSA concentration, homogenization pressure, and number of cycles onto to the particle size, zeta potential, drug loading, and in vitro drug release profile of developed nanoparticles was optimized. Herein, optimized NPs (F5 formulation) possessing the particle size of 165 ± 8.53 nm, PDI of 0.126, and zeta potential of − 22.4 ± 3.5 mV were obtained as spherical shaped. Additionally, in vitro release profile of F5 formulation demonstrated the biphasic pattern initiated with burst release (12% after 2 h) followed by sustained release (45% after 48 h) at pH 7.4. Furthermore, in vitro cytotoxicity study of optimized formulation revealed potential cytotoxicity at dose-dependent manner in which IC50 of PTX-HSA NPs displayed 12.23 ± 2.4 µg/ml and 11.31 ± 2.2 µg/ml against MCF-7 and MDA-MB-231 human breast cancer cell lines, respectively, irrespective to free drug. Stability study of F5 lyophilized powder further showed well-maintained integrity, potentivity, and stability. Conclusively, process parameter optimization and in vitro characterization of developed PTX-HSA NPs further provide suitable platform for industrial or scale-up production. [ABSTRACT FROM AUTHOR]

Formulation of biocontrol agents including bioinoculants and biopesticides is a critical factor which determines crop growth and yield that are cultivated by organic agriculture practices. Trichoderma viride is the most commonly used biocontrol agent against diverse plant pathogens associated with various crops. In the present study, the effect of formulation like gel matrix prepared from natural products and water in oil emulsion of Trichoderma viride on the post treatment persistence adapting dilution method and soil dilution method was studied. The maximum frequency of occurrence was recorded in all the formulation over the control, and high frequency of occurrence was recorded in water in oil formulation and followed by biogel formulation. The effect of metallic nanoparticles on the formulation efficacy was also studied which reveals all the formulation could retain the viability. The effect of formulation on the biocontrol efficacy of Fusarium oxysporum and Alternaria alternata adapting soil dilution method reveals all the formulation retarded the tested pathogenic fungal colonies, and the biogel formulation of Trichoderma viride with nanoparticles treatment showed the best compatibility on decomposition of organic wastes. The study is highly recommended because of the high rate of persistence of compatibility resistant to nanoparticle treatment and best biocontrol efficacy. [ABSTRACT FROM AUTHOR]

Blossom blight is the most destructive strawberry disease worldwide. Minerals play a significant role in the control of plant diseases. The antimicrobial effects of salt solutions have been widely documented for the management of various plant diseases. This study aims to evaluate the impact of mineral compounds on strawberry blossom blight caused by Botrytis cinerea. Ten mineral compounds were used to evaluate the inhibition of mycelial growth, mycelium deformation, and conidia production of B. cinerea in vitro. Five mineral compounds, aluminum chloride, aluminum sulfate, sodium metabisulfite, borax, and potassium sulfate, were chosen based on in vitro results for further study. Linseed oil, castor oil, and three inert materials were used to formulate these minerals. The number of infected and healthy flowers was used to evaluate the efficacy of the mineral compound formulations in the control of strawberry blossom blight under greenhouse conditions. The observed efficacy was between 33%—51%. The most effective formulations of mineral compounds were aluminum chloride and aluminum sulfate formulated with castor oil by two and one parts per thousand, respectively. The results show that these two mineral compounds can be used as alternative to fungicides for the control of B. cinerea especially in organic production of strawberry. [ABSTRACT FROM AUTHOR]

Animal proteins from meat and its stuffs have recently been one of main concerns in the drive for sustainable food production. This viewpoint suggests that there are exciting prospects to reformulate meat products that are produced more sustainably and may also have health benefits by substituting high-protein nonmeat ingredients for some of the meat. Considering these pre-existing conditions, this review critically reviews recent data on extenders from several sources, including pulses, plant-based components, plant byproducts, and unconventional sources. We used the related keywords from Scopus-database without limiting the publishing date. With an emphasis on how these findings may impact the sustainability of meat products, it sees them as a great chance to enhance the functional quality and technological profile of meat. Therefore, to promote sustainability, meat alternatives such as plant-based meat equivalents are being made available. To boost consumer acceptability of these goods, further initiatives should also be developed to enhance the functioning of these innovative food items and increase public knowledge of plant-based meat analogues. [ABSTRACT FROM AUTHOR]

Summary: Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system. [ABSTRACT FROM AUTHOR]

Whilst there is concern about the role of social media use in adolescent and emerging adult development, there is a gathering consensus that how individuals spend their time on social media may be more important than how much time they spend on it, with potential benefits and risks of engagement. In addition, there is growing interest in a broader range of outcomes, including wellbeing, mental health and educational attainment. Building on this research, the present study offers a new, theory-driven investigation of complex cross-sectional associations between users' motivations for social media use and wellbeing, as well as users' motivations and academic outcomes. Specifically, self-perceived stress and Grade Point Average scores were regressed on self-reported social media motivations, using data collected from nearly 6000 Chinese undergraduate students. In line with our predictions and a transdiagnostic cognitive behavioral conceptualization of social media use, social enhancement/approach motivations ("to make new friends") and escapist motivations ("to kill time") were associated with lower and higher levels of self-reported stress, respectively. In addition, academic motivations for social media use (i.e., "for academic purposes") were associated with higher educational attainment. These effects persisted after controlling for a number of potential confounders, including key demographic and socioeconomic variables. Whilst the cross-sectional design precludes inferences about underlying directions of causality, these findings suggest that inter-individual differences in motivations for engagement may be crucial in understanding the role that social media plays in adolescent and emerging adult life and generate predictions for future longitudinal and cross-sectional studies. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of yellow light-emitting diode (LED) irradiation at 590 nm, alone or in combination with anti-inflammatory active substances against ultraviolet (UV)-induced inflammation in keratinocytes. HaCaT keratinocytes were pretreated with LED yellow light (590 nm) alone or in combination with an antiinflammatory active substance such as glycerophosphoinositol choline (GC), extract of grains of paradise (Aframomum melegueta Schum, AM), or a bisabolol and ginger root extract mixture (Bb-GE) before UVB irradiation. Following each treatment, we measured the levels of inflammatory mediators secreted by keratinocytes. HaCaT keratinocytes treated with UVB (300 mJ cm−²) and then cultured for 24 h exhibited significantly upregulated expression of proinflammatory factors, including interleukin (IL)-1α, prostaglandin E2 (PGE2), and IL-8. After pretreatment with 590 nm LED, UVB-induced inflammatory responses were significantly inhibited. Co-pretreatment with 590 nm LED irradiation and GC further inhibited the expression of IL-1α and IL-8. IL-8 expression was inhibited by co-pretreatment with 590 nm LED irradiation and AM, whereas PGE2 expression was inhibited by co-pretreatment with 590 nm LED irradiation and Bb-GE. Co-treatment with 590 nm LED irradiation and various active substances modulated UVB-induced inflammation in keratinocytes, suggesting the potential application of this approach to prevent damage caused by voluntary sun exposure in daily life. [ABSTRACT FROM AUTHOR]

One major limitation of effective vaccine delivery is its dependency on a robust cold chain infrastructure. While Vesicular stomatitis virus (VSV) has been demonstrated to be an effective viral vaccine vector for diseases including Ebola, its −70 °C storage requirement is a significant limitation for accessing disadvantaged locations and populations. Previous work has shown thermal stabilization of viral vaccines with a combination of pullulan and trehalose (PT) dried films. To improve the thermal stability of VSV, we optimized PT formulation concentrations and components, as well as drying methodology with enhanced vacuum drying. When formulated in PT films, VSV can be stored for 32 weeks at 4 °C with less than 2 log PFU loss, at 25 °C with 2.5 log PFU loss, and at 37 °C with 3.1 log PFU loss. These results demonstrate a significant advancement in VSV thermal stabilization, decreasing the cold chain requirements for VSV vectored vaccines. [ABSTRACT FROM AUTHOR]

Fire blight caused by bacterium Erwinia amylovora is one of the most damaging diseases of apple and pear trees and many other plant species of the Rosaceae family. So far, it has been detected in almost all areas of pome fruit cultivation and in some regions it causes economic damage every year. Plant protection against fire blight is aimed at both preventing their infection and controlling the disease. However, the protection of plants against bacteriosis is generally difficult due to the small range of plant protection products and the growing doubts about their safety for the environment. Limitations related to their use have resulted in an increased interest in alternative methods, including the method of biological protection using various microorganisms. The first research on biological control agents was conducted in the USA about 100 years ago. Currently, it is also carried out in other countries, especially where fire blight causes economic losses. Commercial products whose active ingredients are mainly bacteria have already been developed. This work is a review of the studies and achievements in this field from its beginnings focusing on the Gram-negative bacteria and bacteriophages as a biocontrol agents. [ABSTRACT FROM AUTHOR]

Background: In recent years, public awareness of healthy diets has significantly increased, leading to a rise in the consumption of nutritional supplements. Among these, omega-3 fatty acids have become particularly popular. n − 3 polyunsaturated fatty acids (PUFAs) are widely distributed in marine and terrestrial environments. The primary sources of marine n − 3 fatty acid supplements are oily fish, such as anchovies, sardines and mackerel. Recently, they have drawn considerable attention for their potential therapeutic benefits in treating a range of illnesses, including cancer, neurological disorders, cardiovascular diseases, immunological and reproductive diseases, respectively. Main text: This study explores the many activities of n − 3 PUFAs, highlighting their importance in cellular processes that include signaling pathways, cell membrane integrity and structural maintenance. These fatty acids significantly regulate important physiological functions including the neurological system, blood pressure control, hematopoiesis, glucose metabolism and inflammatory responses. The latter highlights the wide therapeutic range of n − 3 PUFAs is especially notable considering the implications for controlling inflammatory disorders. Furthermore, the chemistry and dietary sources of omega-3 fatty acids are clarified in this review, which also sheds light on the complex molecular pathways that support the therapeutic efficacy of these fats and their bioavailability. The most recent information on the FDA's approval of omega-3 oils for use in formulation development highlights the compounds' adaptability and potential influence on the development of novel medications. Conclusion: A thorough analysis of omega-3 polyunsaturated fatty acids reveals both their remarkable therapeutic potential against a variety of diseases and their essential place in a normal diet. This study adds to the increasing amount of data that supports the use of n − 3 PUFAs in preventative and therapeutic approaches that are meant to improve human health and well-being by clarifying their mechanisms of action and emphasizing their applicability in formulation and development. [ABSTRACT FROM AUTHOR]

There have been significant advances in the formulation and stabilization of proteins in the liquid state over the past years since our previous review. Our mechanistic understanding of protein-excipient interactions has increased, allowing one to develop formulations in a more rational fashion. The field has moved towards more complex and challenging formulations, such as high concentration formulations to allow for subcutaneous administration and co-formulation. While much of the published work has focused on mAbs, the principles appear to apply to any therapeutic protein, although mAbs clearly have some distinctive features. In this review, we first discuss chemical degradation reactions. This is followed by a section on physical instability issues. Then, more specific topics are addressed: instability induced by interactions with interfaces, predictive methods for physical stability and interplay between chemical and physical instability. The final parts are devoted to discussions how all the above impacts (co-)formulation strategies, in particular for high protein concentration solutions.' [ABSTRACT FROM AUTHOR]

In a lyophilized protein/disaccharide system, the ability of the disaccharide to form a homogeneous mixture with the protein and to slow the protein mobility dictates the stabilization potential of the formulation. Human serum albumin was lyophilized with sucrose or trehalose in histidine, phosphate, or citrate buffer. 1H T1 relaxation times were measured by solid-state NMR spectroscopy and were used to assess the homogeneity and mobility of the samples after zero, six, and twelve months at different temperatures. The mobility of the samples decreased after 6 and 12 months storage at elevated temperatures, consistent with structural relaxation of the amorphous disaccharide matrix. Formulations with sucrose had lower mobility and greater stability than formulations with trehalose. [ABSTRACT FROM AUTHOR]

Seborrheic dermatitis (SD) impacts a diverse demographic, with treatment effectiveness and suitability varying across hair types and cultural practices. Available shampoo treatments contain surfactants that compromise hair moisture and integrity as well as requiring frequent use, which may not align with the routines of various hair types and cultural hair care practices. Most available topical foams and gels contain high concentrations of drying alcohols that damage hair color and moisture. Newly US Food and Drug Administration (FDA)-approved roflumilast 0.3% foam presents a significant advancement in the treatment of SD owing to its pH-balanced, residue-free formulation that is suited for all hair types, including patients with curly or coiled hair. It presents a culturally inclusive treatment option that offers effective management of SD while maintaining hair health and respecting diverse hair care needs and practices. [ABSTRACT FROM AUTHOR]

Adalimumab (ADL, Humira®, reference product), an anti-TNF-α biologic, has transformed the treatment of chronic, immune-mediated inflammatory diseases. However, the high cost of ADL therapy has driven the development of more affordable ADL biosimilars, agents with no clinically meaningful differences from the reference product. This review summarizes the product attributes of reference ADL and the nine ADL biosimilars approved and available in the USA in relation to patient experience of injection-site pain (ISP). Product formulation, delivery volume and device features (e.g., type and needle gauge size) influence patient experience of ISP with potential clinical consequences. Citrate-free formulations generally cause less ISP; injection volumes of > 1.5 ml may be associated with increased ISP. Reference ADL and all ADL biosimilars offer a citrate-free formulation, and reference ADL and four ADL biosimilars offer a high-concentration solution that allows a smaller injection volume. All available ADL products are injected subcutaneously using either a pre-filled pen (PFP) or pre-filled syringe (PFS). Patients prefer the PFP, but the PFS permits better control over the speed and duration of injection. Smaller (29-gauge) needle outer diameter is associated with less ISP; reference ADL and seven ADL biosimilars offer a device with a 29-gauge needle. In the USA, an approved biosimilar can be designated "interchangeable," allowing pharmacy-level substitution, where state law permits. In the USA, two ADL biosimilars have received interchangeability designation; others are seeking interchangeability designation from the Food and Drug Administration (n = 2), are being evaluated in clinical studies to support interchangeability (n = 2), or do not have/are not seeking interchangeability designation (n = 3). Product-related attributes influence patient experience of ISP caused by subcutaneous ADL injection. Reference ADL and ADL biosimilar products differ in their attributes, so discussion with patients about treatment options is essential to optimize adherence and outcomes. [ABSTRACT FROM AUTHOR]

Bactrocera dorsalis (Diptera: Tephritidae), the primary pest of guava (Psidium guajava), damages numerous horticulture fruits in tropical and subtropical regions. The use of insecticides for the management of this pest adversely affect agro-ecosystem and has environmental consequences. The repellent activity of Salix alba (Willow) bark extract and a Guava oil-based formulation was investigated to protect guava fruit from infestation by the fruit fly, B. dorsalis. In the laboratory experiments, the efficacy of these natural repellents was assessed. Bactrocera dorsalis significantly deterred guava fruit treated with S. alba formulation as compared to the extract alone, which exhibited significant anti-feeding activity, and caused a decline in fecundity rate by 60% and larval mortality rate by 90%. When females were allowed to oviposit on guava fruits in laboratory and field after mating, these flies preferred fruits for oviposition that were not sprayed with S. alba-guava oil formulation. GC-MS analysis showed esters and terpenes as the main components for exhibiting repellent property in S. alba-based formulation. Hence, guava oil formulation of S. alba showed a complete protection of guava fruits against B. dorsalis in the laboratory conditions to control infestation by B. dorsalis. Further research and field trials are warranted to optimize the application methods and assess the long-term effects on crop yield and overall fruit quality. [ABSTRACT FROM AUTHOR]

The incorporation of biological control agents (BCAs) such as Trichoderma spp. in agricultural systems favors the transition towards sustainable practices of plant nutrition and diseases control. Novel bioproducts for crop management are called to guarantee sustainable antagonism activity of BCAs and increase the acceptance of the farmers. The encapsulation in polymeric matrices play a prominent role for providing an effective carrier/protector and long-lasting bioproduct. This research aimed to study the influence of biopolymer in hydrogel capsules on survival and shelf-life of T. koningiopsis. Thus, two hydrogel capsules prototypes based on alginate (P1) and amidated pectin (P2), containing conidia of T. koningiopsis Th003 were formulated. Capsules were prepared by the ionic gelation method and calcium gluconate as crosslinker. Conidia releasing under different pH values of the medium, survival of conidia in drying capsules, storage stability, and biocontrol activity against rice sheath blight (Rhizoctonia solani) were studied. P2 prototype provided up to 98% survival to Th003 in fluid bed drying, faster conidia releasing at pH 5.8, storage stability greater than 6 months at 18 °C, and up to 67% of disease reduction. However, both biopolymers facilitate the antagonistic activity against R. solani, and therefore can be incorporated in novel hydrogel capsules-based biopreparations. This work incites to develop novel biopesticides-based formulations with potential to improve the delivery process in the target site and the protection of the active ingredient from the environmental factors. [ABSTRACT FROM AUTHOR]

Amblyomma ticks pose a significant public health threat due to their potential to transmit pathogens associated with rickettsial diseases. (E)-2-octenal, a compound found in donkeys (Equus asinus), exhibits strong repellent properties against Amblyomma sculptum nymphs under laboratory conditions. This study assessed the effectiveness of the (E)-2-octenal in wearable slow-release devices for personal human protection against Amblyomma ticks under natural conditions. Slow-release devices treated with (E)-2-octenal and untreated controls were prepared and tested on two volunteers walking through a tick-infested area in Goiania, Brazil. The experiment was conducted twice daily for three series of 10 days, with each volunteer wearing two devices attached to each leg, one on the ankle and one just above the thigh. Volunteers with control and treated devices exchanged them between rounds. Also, the daily release rate of (E)-2-octenal from the slow-release devices was determined in the laboratory, increasing significantly from 0.77 ± 0.14 µg/day on the first day to 9.93 ± 1.92 µg/day on the 4th day and remaining constant until the 16th day. A total of 5409 ticks were collected from both volunteers. Treated devices resulted in recovering fewer ticks (n = 1,666; 31%) compared to untreated devices (control: n = 3,743; 69%). (E)-2-octenal effectively repelled Amblyomma spp. larvae, A. sculptum adults, and exhibited pronounced repellency against A. dubitatum nymphs and adults. These findings suggest the potential of (E)-2-octenal delivered by wearable slow-release devices as a green-based repellent. Further improvements, however, are necessary to provide better protection for humans against A. sculptum and A. dubitatum in field conditions. [ABSTRACT FROM AUTHOR]

Purpose: Silicone oil droplets in biopharmaceutical products can originate from sources such as siliconized surfaces of primary packaging materials, potentially triggering the formation of protein–silicone oil particles. To better understand this phenomenon, there is a need for particle detection devices that cannot only distinguish between protein particles and silicone oil droplets but also determine particle sizes ranging from nanometers to micrometers. Method: In this study, we conducted a systematic assessment of imaging flow cytometry (IFC) using the FlowSight® instrument. Our first step was to investigate specific instrument settings using protein particle samples spiked with silicone oil for particle classification. Based on these findings, we established suitable, harmonized working templates. Next, we evaluated the instrument’s accuracy and precision for particle sizes within the range of 0.5 to 100 µm and their respective concentrations. Finally, we investigated any constraints in particle concentration within this size range. Results: This study demonstrates that IFC can effectively distinguish protein particles from silicone oil droplets when the latter is labeled with a specific fluorescent dye. Our findings suggest that fluorescently labeled particles ≥ 0.5 µm can be reliably detected. Through our research, we determined the particle concentration limits for each particle size in the range of 0.5 to 10 µm, with a precision deviation of less than 15%. However, our study also revealed that IFC exhibited insufficient accuracy for the tested particle concentrations within this size range. Additionally, we showed that the measurements were significantly influenced by the instrument settings. Conclusion: Although we addressed numerous new aspects to enhance the experimental procedure of IFC measurements, we conclude that IFC is not an ideal technique for quantifying sub-visible particles. Instead, it should be employed to provide supportive characterization data in conjunction with commonly used sub-visible particle detection methods. If distinguishing between protein particles and silicone oil droplets is essential, IFC is an option, as long as the fluorescent dye is carefully selected. [ABSTRACT FROM AUTHOR]

High-speed rail has been operating in more than 25 countries (mainly in Asia, Europe and North America), and has become an important part of global economic development. However, the cleaning and maintenance of high-speed rail is a comprehensive task, which may easily cause environmental pollution. This study aims to analyze and improve the sustainability of the formulation and production process of a concentrated complex enzyme detergent used as the maintenance agent for high-speed trains via the life cycle assessment (LCA) method. The eFootprint software system with built-in China, European and Swiss Ecoinvent databases was used to establish the LCA model with the system boundary being from cradle to gate. The LCA model showed that the production of 1 kg of concentrated detergent generates the global warming potential of 2.53 kg CO2 eq, and other environmental emissions including acidification potential of 0.01 kg SO2 eq, eutrophication potential of 3.76E-03 kg PO43−eq, inhalable inorganic matter of 3.17E-03 kg PM2.5 eq, ozone depletion potential of 5.3E-06 kg CFC-11 eq, photochemical ozone formation potential of 3.44E-03 kg NMVOC eq, primary energy demand of 3.17 MJ, abiotic depletion potential of 4.97E-6 kg antimony eq, and water use of 0.84 kg. LCA results are not strongly dependent to the assumptions of the research, and the uncertainties of LCA results are between 8 and 16%, which is mainly due to the regional differences in technology sources, the year of technical data collection, and the representativeness of technology collection companies. Carbon footprint analysis showed that the production processes of enzyme stabilizer (glycerol) and surfactants contributed the most, while changes in power consumption during production and transportation distance of raw materials had limited effect on total carbon emissions. Therefore, the formulation of the concentrated complex enzymatic detergent was improved based on the LCA results. The new formulations with less enzyme stabilizer showed similar detergency to the original formulation. The new formulations could reduce carbon emissions by 5,500–9,200 tons per year and save between $4.4 and $7.4 million in annual production of 10,000 tons. [ABSTRACT FROM AUTHOR]

Policy design approaches currently pay insufficient attention to feedback that occurs during the design process. Addressing this endogenous policy design feedback gap is pressing as policymakers can adopt 'low-fidelity' design approaches featuring compressed and iterative feedback-rich design cycles. We argue that within-design feedback can be oriented to the components of policy designs (instruments and objectives) and serve to reinforce or undermine them during the design process. We develop four types of low-fidelity design contingent upon the quality of feedback available to designers and their ability to integrate it into policy design processes: confident iteration and stress testing, advocacy and hacking, tinkering and shots in the dark, or coping. We illustrate the utility of the approach and variation in the types, use, and impacts of within-design feedback and low-fidelity policy design through an examination of the UK's Universal Credit policy. [ABSTRACT FROM AUTHOR]

Introduction: Potentially harmful excipients (PHEs) for children have been reported and the need for information collection has been advocated. However, studies on the actual occurrence of adverse events are limited. This study investigated the quantitative exposure of PHEs via injection and their association with adverse events in children under 2 years of age. Materials and Methods: As a single-center observational study, children aged 0–23 months received injectable drugs from April 1, 2018, to March 31, 2023 were included. Information on PHE exposure and adverse events after administration were extracted from medical records. Sodium benzoate, benzyl alcohol, ethanol, glycerol, lactose, polyethylene glycol paraben, polysorbate, propylene glycol, sorbitol, sucrose, sulfite, and thimerosal were selected as PHEs. Results and Discussion: 6265 cases, 333,694 prescriptions, and 368 drugs (264 ingredients) were analyzed. The median age was 0.63 years (interquartile range [IQR] 0.1–1.1). 72,133 prescriptions, 132 drugs and 99 ingredients contained PHE; 2,961 cases exposed to PHE and 1825 cases exceeding permitted daily exposure. The drug with the highest number of exposure cases was hydroxyzine, and the highest number of prescriptions was heparin (both drugs contain benzyl alcohol). In association between adverse events and PHE exposure, higher doses in cases of adverse event occurrence were found in benzyl alcohol, glycerol, polyethylene glycol, and polysorbate exposed cases. Among thimerosal-exposed cases, "developmental delay" was more frequent in exposed cases, but the causal relationship was unknown. Further investigation is needed to clarify the relationship between adverse events and PHE exposure. Additionally, more precise information on PDE for pediatrics including neonates is necessary. [ABSTRACT FROM AUTHOR]

The term cosmetics refers to any substances or products intended for external application on the skin with the aim of protection and better appearance of the skin surface. The skin delivery system promotes the controlled and targeted delivery of active ingredients. The development of this system has been driven by challenges encountered with conventional cosmeceuticals, including low skin retention of active components, limited percutaneous penetration, poor water dispersion of insoluble active ingredients, and instability of effective components. The aim is to create cosmeceuticals that can effectively overcome these issues. This review focuses on various nanocarriers used in cosmeceuticals currently and their applications in skin care, hair care, oral care, and more. The importance of nanotechnology in the sphere of research and development is growing. It provides solutions to various problems faced by conventional technologies, methods, and product formulations thus taking hold of the cosmetic industry as well. Nowadays, consumers are investing in cosmetics only for better appearance thus problems like wrinkles, ageing, hair loss, and dandruff requires to be answered proficiently. Nanocarriers not only enhance the efficacy of cosmeceutical products, providing better and longer-lasting effects, but they also contribute to the improved aesthetic appearance of the products. This dual benefit not only enhances the final quality and efficacy of the product but also increases consumer satisfaction. Additionally, nanocarriers offer protection against UV rays, further adding to the overall benefits of the cosmeceutical product. Figure 1 represents various advantages of nanocarriers used in cosmeceuticals. Nanotechnology is also gaining importance due to their high penetration of actives in the deeper layers of skin. It can be said that nanotechnology is taking over all the drawbacks of the traditional products. Thus, nanocarriers discussed in this review are used in nanotechnology to deliver the active ingredient of the cosmeceutical product to the desired site. [ABSTRACT FROM AUTHOR]

Fault movement during earthquakes is a geotechnical phenomenon threatening buried pipelines and with the potential to cause severe damage to critical infrastructures. Therefore, effective prediction of pipe displacement is crucial for preventive management strategies. This study aims to develop a fast, hybrid model for predicting vertical displacement of pipe networks when they experience faulting. In this study, the complex behavior of soil and a buried pipeline system subjected to a normal fault is analyzed by using an artificial neural network (ANN) to generate predictions the behavior of the soil when different parameters of it are changed. For this purpose, a finite element model is developed for a pipeline subjected to normal fault displacements. The data bank used for training the ANN includes all the critical soil parameters (cohesion, internal friction angle, Young's modulus, and faulting). Furthermore, a mathematical formula is presented, based on biases and weights of the ANN model. Experimental results show that the maximum error of the presented formula is 2.03%, which makes the proposed technique efficiently predict the vertical displacement of buried pipelines and hence, helps to optimize the upcoming pipeline projects. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the impact of formulation (gel vs cream) and microneedle characteristics (length, number) on permeation of metronidazole through excised microneedle-treated skin. The long-term goal is to apply these results towards a pharmacokinetic study in human subjects with diverse skin types, using in vitro flux data to determine dosing conditions and ultimately establish in vitro-in vivo correlations. Methods: Metronidazole release from 0.75% gel and cream was quantified with flow-through diffusion cells, using a cellulose membrane. Excised porcine skin was treated with stainless steel microneedles (500 or 800 μm length), to create 50 or 100 micropores. Metronidazole gel or cream was applied to microneedle-treated skin and replaced every 48 h for up to 7 days. Metronidazole permeation was quantified using HPLC. Intact skin (no microneedle treatment) served as controls. Results: Metronidazole release was faster from the gel vs cream. At 7 days there was no difference between gel vs cream in total metronidazole permeated through intact skin. For both formulations, metronidazole permeation was significantly higher (vs intact skin) following microneedle application, regardless of microneedle length or micropore number. Increasing microneedle length and micropore number enhanced MTZ permeation multiple fold for both gel and cream. The greatest enhancement in total permeation for both formulations was achieved with the 800 μm MN, 100 micropore condition. Conclusions: Formulation and microneedle conditions both impacted metronidazole permeation. These data will be used to estimate in vivo serum concentrations after applying metronidazole to microneedle-treated skin in humans. [ABSTRACT FROM AUTHOR]

Background: Chickpea plant (Cicer arietinum L.) is an important legume crop that is vulnerable to various fungal pathogens causing significant yield losses. Among them, Fusarium equiseti is a pathogen that has started to raise concern. In contrast, Trichoderma species have been explored for their ability to control such pathogens. In this study, the efficacy of a novel seed treatment formulation was explored for controlling F. equiseti in chickpea plants. The formulation was designated to enhance growth in chickpea plants as well as the ability to protect plants from infection. In addition, this formulation was tested for its effectiveness in maintaining the conidia of the antagonist in the soil after sowing. Results: Applying the Trichoderma asperellum-based formulation promoted growth, as well as root and aerial biomass. In seedlings derived from treated seeds, the shoot length increased by 36.8%, and the average number of leaves also increased than the control. Following evaluation of disease severity and the foliar alteration index (FAI), a protective effect was noted, as the symptoms of Fusarium were significantly reduced in treated plants than the infected control. Re-isolation from plants infected with F. equiseti was successful in the roots (72.7%), root crown (84.5%), stem (64.4%), and even in petioles (36.1%). Conclusions: Due to both direct antagonist activity and indirect growth promotion ability, the findings suggested that tested formulation can be a sustainable and eco-friendly alternative to chemical fungicides for managing F. equiseti in chickpea seeds. [ABSTRACT FROM AUTHOR]

Background & Purpose: Different methods have been exploited to generate amorphous solid dispersions (ASDs) of poorly water-soluble drugs. However, the impact of processing methods on drug stability and dissolution hasn't been studied extensively. The purpose of the current study is to investigate the impact of the two common ASD processing methods, hot-melt extrusion (HME) and spray drying, on the chemical/physical stability and supersaturation of Posaconazole (Posa) based ASDs. Methods & Results: ASDs with 25% drug loading in hydroxypropylmethylcellulose acetate succinate were prepared using HME, and two types of spray dryers, a Procept Sprayer (ASD-Procept) and a Nano Sprayer (ASD-Nano). The relative physical stability of these ASDs upon exposure to heat and crystalline API seeding followed the order: ASD-Nano > ASD-Procept ≈HME. ASD-Procept and ASD-Nano showed similar chemical stability, slightly less stable than HME under 40°C/75%RH. All three ASDs demonstrated similar supersaturation induction times, and de-supersaturation kinetics with or without crystalline seeds. Conclusions: Posa ASDs prepared via spray drying were chemically less stable compared with HME, which can be attributed to their smaller particle size and hollow structure allowing oxygen penetration. For ASD-Procept and HME, the detailed phase changes involving recrystallization of amorphous Posa and a solid-solid phase transition from Posa Form I to Form Ia during the seed-induced studies were proposed. Similar dissolution and supersaturation-precipitation kinetics of three Posa ASDs indicated that any residual nanocrystals in the bulk ASDs were not enough to induce crystallization to differentiate ASDs made by three processing methods. [ABSTRACT FROM AUTHOR]

Background: Skin cancer is becoming a public health concern due to increased exposure to environmental pollutants and UV rays, among other factors. In India, skin neoplasms constitute 2–3% of all human cancer cases, whereas in the USA, 2–3 million cases of non-melanoma skin cancer are reported annually. Various drugs are available in the market for treating skin cancer. Imiquimod (IMQ) is one such drug approved by the USFDA for managing basal cell malignancy, external genital warts, and actinic keratosis. The conventional dosage form of IMQ cream has several side effects that can lead to therapy interruption. Therefore, the present work aims to develop an IMQ nanoemulsion with improved solubility, in vitro drug release and stability. Nanoemulsion was formulated using oleic acid/rose oil, with polysorbate 20/propylene glycol selected as the oil phase and Smix, respectively. Optimization carried out using a 32 factorial design with the aid of a quadratic model. Characterization was conducted for parameters, namely viscosity, pH, drug content, globule size, zeta potential and entrapment efficiency. Thermodynamic stability studies were conducted to assess the stability of the formulation. Furthermore, the optimized system was subjected to TEM analysis, in vitro drug release and in vitro cytotoxicity assay (MTT assay). Results: Nanoemulsions were found to be in the size range of 152.80–470.13 nm and exhibited a spherical shape. Zeta potential values ranged from − 28.93 to − 58.48 mV. DSC measurements indicated the complete solubilization of IMQ in the nanoemulsion system. The optimized formulation F1 displayed the following characteristics: a globule size < 200 nm, a zeta potential > − 55 mV, a polydispersity index < 0.2, % drug content of 102.89 ± 1.06, % entrapment efficiency of 97.59 ± 0.24, a pH of 4.77 ± 0.06, and a viscosity of 4.06 ± 0.06 poise. In vitro IMQ release studies of nanoemulsion and commercial cream showed approximately 70% and 34% drug release, respectively, at the end of 8 h. Moreover, the in vitro cytotoxicity assay depicted that F1 exhibited greater cytotoxic potential compared to the commercial formulation against the A431 cell line. Conclusion: The present investigation showed a significant improvement in in vitro drug release of the BCS class IV drug IMQ and enhanced cytotoxic activity against cancerous cells. IMQ-loaded nanoemulsion represents a promising vehicle for delivering treatment to the skin for treating skin cancer. [ABSTRACT FROM AUTHOR]

Background: Symptom-based diagnostic formulations significantly influence psychological treatment; however, they are not without limitations. Employing a transdiagnostic approach may address these shortcomings. For transdiagnosis to gain wider acceptance, it is crucial to establish a meaningful connection between transdiagnostic measures and symptom expression. Two potential transdiagnostic measures, the Event Characteristics Questionnaire (ECQ) and the Basic Psychological Needs Satisfaction and Needs Frustration Scale (BPNSNFS), were identified based on theories of psychopathology. The present study investigated whether the unique within-person characteristics assessed by each scale could indicate symptom expression over time. Method: Online questionnaires were completed by 290 international participants (86% female) who had experienced a significant event within the past 12 months. The measures included the ECQ, BPNSNFS, and clinical assessments of depression, anxiety, and anger. Results: Results indicated that only the BPNSNFS demonstrated a meaningful connection with symptom expression. A cross-lagged structural analysis revealed that participants experiencing higher levels of needs frustration reported higher levels of depression and anger. Conversely, those reporting higher levels of needs satisfaction reported lower levels of depression and anxiety. Conclusions: The findings suggest that the BPNSNFS can serve as a valuable transdiagnostic tool to enhance the delivery of measure-based care. Further research should continue to explore the clinical role of basic psychological needs. [ABSTRACT FROM AUTHOR]

Amphotericin B (AmB) is a membrane-acting antibiotic used for the treatment of fungal and protozoal infections. AmB exists in various molecular forms, i.e., monomeric, super-aggregated, and oligomeric forms, where oligomeric forms are highly toxic because of their relative affinity toward cholesterol present over human cell membrane. Hence, the objective of our research work was to study the aggregation state of AmB in two different nanoformulations, i.e., solid lipid nanoparticles (SLNs) and zein-based nanoparticles (PNPs), with the aim of enhancing the fraction of less toxic form of AmB, and a comparative study was performed. The zein and glyceryl monostearate can intercalate the polyenic domain of AmB and thereby hinder the hydrophobic attractions between the AmB molecules, which allows their existence in monomeric forms. The particle size of AmB-SLNs and AmB-PNPs were 378.90 ± 9.50 nm and 184.90 ± 6.00 nm, while zeta potential was −34.97 ± 0.51 mV and +28.93 ± 2.29 mV, respectively. In vitro release studies showed more controlled release of AmB from PNPs (52.48 ± 1.07%) as compared to SLNs (86.33 ± 0.93%). The predominant aggregation state of AmB in both formulations was determined by UV–visible and circular dichroism spectrophotometry, where a higher degree of monomerization of AmB was reported in AmB-SLNs as compared to AmB-PNPs. Toxicity of the nanoformulations was evaluated through hemolysis test, where the results suggested that AmB-SLNs and AmB-PNPs were less hemolytic as compared to pure AmB. The nanoformulations demonstrated the predominant monomeric form of AmB, which may offer higher selectivity index toward microbial membrane. [ABSTRACT FROM AUTHOR]

Trichoderma, a well-known fungal genus and opportunistic plant symbiont, is a quintessential alternative to chemicals with great potential to minimize disease incidence. The mycoparasitic ability along with antibiosis and induction of host immunity are the main mechanisms of biocontrol by this fungus. Fungi belonging to genus Trichoderma have been identified as potential biocontrol agents due to majority of isolated antifungal bioactive compounds. This review summarizes the biological control activity exerted by Trichoderma spp. against plant pathogenic fungi, bacteria, viruses, nematodes and insect pests. In addition, the research on formulations advocates that encapsulation could be a promising tool for increasing efficacy and durability of these fungi under field conditions. Further, advances in different areas of science and technology would strengthen the future research on Trichoderma-based products for its efficient use in agriculture. [ABSTRACT FROM AUTHOR]

For this preliminary study, the lubricating properties of six formulations containing used cooking oils were tested. The physicochemical properties involved were determined by measuring viscosities at temperatures between 0 and 40 °C as well as by calculating adhesion energies. The formwork/concrete interface was then studied on the steel surface by means of both tribological measurements and analysis of facing quality at 1 day and 7 days after stripping. The results obtained were compared with a marketed vegetable-based oil. The physicochemical results revealed attractive parameters despite a viscosity that remained high. The liquid/vapor surface tensions and wettabilities measured satisfied the recommendations, i.e., greater than 30 mN/m and less than 30°. The selected formulation offered the best compromise between composition and the physicochemical recommendations. At the formwork/concrete interface and for a scraped application, satisfactory criteria were derived, with a 35% reduction in friction and an acceptable facing quality for this initial study. [ABSTRACT FROM AUTHOR]

Several plant growth–promoting bacteria (PGPB) are gram-negative, and their cell viability is affected during the bio-inoculant production. Hence, formulation-drying processes provide challenges that limit the adoption of these beneficial microorganisms in sustainable agricultural production. Among delivery system strategies for gram-negative PGPB, the encapsulating cells in biopolymeric materials are emerging as a promising alternative. This research aims to evaluate the effect of additives and crosslinking agents on the survival of the consortium of Herbaspirillum frisingense AP21, Azospirillum brasilense D7, and Rhizobium leguminosarum T88 in hydrogel capsules. Three crosslinkers and diverse potential drying protectors were tested. Calcium gluconate provides notable consortium survival advantages regarding colony-forming units (CFUs) (losses of up to 4 log CFU) compared to calcium lactate and calcium chloride (up to 6 log CFU). Additives such as skimmed milk, whey protein, and Gelita® EC improve the recovery of viable cells after the drying process, demonstrating an increase in cell survival of the three bacteria by up to 4 log CFU. The combination of these substances into a capsule prototype extends the storage stability of bacterial consortium up to 3 months at 18 ± 2 °C. This study expands the knowledge for formulating gram-negative PGPB consortium, regarding the crosslinker and drying protector relationship on encapsulation processes with drying survival and further storage stability performance. Key points: • Hydrogel immobilization formulation approach for PGPB consortium • Enhancing drying survival of gram-negative PGPB consortium • Increasing storage stability of PGPB consortium at 18 °C [ABSTRACT FROM AUTHOR]

As the essential component(s), long-chain perfluorinated or short-chain perfluorinated ionic surfactants are required for effective aqueous film-forming foam (AFFF); nevertheless, the associated qualities of persistent pollution and toxicity have raised significant concerns. It has become critical to develop alternatives to the present fluorine component for AFFF to offset the negative effects. In this study, a short-chain perfluorinated nitrogen-heterocyclic nonionic amine oxide surfactant was combined with hydrocarbon surfactants and additives to prepare an AFFF concentrate. A laboratory technique was developed to evaluate the influence of ingredients on the performance of a 6% AFFF diluent, resulting in an improved AFFF formulation. The performance parameters for pool fire extinguishment and fire resistance of the AFFF formulation were encouraging, including a spreading coefficient of 5.4, foam expansion of 8.11, 25% drainage time of 4.6 min, extinguishing times for forceful application of 58 s, and fire burnback time of 18.6 min. In addition, the AFFF concentrate showed significant freezing resistance when stored at − 20 °C for an extended period of time. The formulation outperformed the technical standard criteria and has the potential to be used as a novel AFFF agent. [ABSTRACT FROM AUTHOR]

We consider Upper Domination, the problem of finding the minimal dominating set of maximum cardinality. Very few exact algorithms have been described for solving Upper Domination. In particular, no binary programming formulations for Upper Domination have been described in literature, although such formulations have proved quite successful for other kinds of domination problems. We introduce two such binary programming formulations, and show that both can be improved with the addition of extra constraints which reduce the number of feasible solutions. We compare the performance of the formulations on various kinds of graphs, and demonstrate that (a) the additional constraints improve the performance of both formulations, and (b) the first formulation outperforms the second in most cases, although the second performs better for very sparse graphs. Also included is a short proof that the upper domination number of any generalized Petersen graph P(n, k) is equal to n. [ABSTRACT FROM AUTHOR]

The study aimed to formulate a nanoemulsion, combine it with aqueous extracts of herbal powders, and test its efficiency as caries-preventing mouthwash. Formulation of nanoemulsion using microfluidizer, characterization of nanoemulsion, minimum inhibitory concentration, adherence test, biofilm assay, and artificial mouth assay was carried out. The biofilms of Streptococcus mutans, Lactobacillus casei, Actinomyces viscosus, and a combination of the three cultures were developed and treated with formulations to study the inhibitory effect of the samples. In artificial mouth assay, human tooth samples were used as surfaces to grow the biofilm of S. mutans, and daily, the teeth were treated with the formulations to test their real-time efficiency. The nanoemulsion was characterized using dynamic light scattering and the size of the particles was within the 100–300 nm range. Above 50 °C, the nanoemulsion combined with plant extract lost its emulsified state within 2 h of incubation, while the nanoemulsion was stable. Nanoemulsion with plant extract inhibited the adherence of L. casei (73%) and biofilm of L. casei (66%). In artificial mouth assay, after 10 days of nanoemulsion, nanoemulsion with plant extract showed DIAGNOdent pen values 3.5 and 2 respectively whereas the negative control value was 14.4 indicating caries initiation. The nanoemulsion with plant extract showed anti-adherence and anti-biofilm activity and hence can be used as a potent anticariogenic mouthwash. [ABSTRACT FROM AUTHOR]

Idelalisib is a phosphatidylinositol 3-kinase delta inhibitor approved by the USFDA and EMA for the treatment of lympholytic lymphoma, B-cell non-Hodgkin lymphoma and lymphocytic lymphoma. The present report describes the validation of simple, rapid, sensitive, and cost-effective spectrofluorimetric methods based on the native fluorescence of the drug in an acidic medium. Fluorescence characteristics of the drug were found to significantly differ in absolute ethanol (λex = 330 and λem = 595 nm) and HCl (λex = 270 and λem = 350 nm) and both methods were validated as per ICH guidelines. The two methods were extremely sensitive, precise and accurate demonstrating excellent linearity in concentration ranges from 0.1–2.0 μg/mL (absolute ethanol) and 0.1–20 μg/mL (HCl). The LOD and LOQ values were found to be 0.015 and 0.045 μg/mL (ethanol) and 0.1615 and 0.4894 μg/mL (HCl). The proposed methods were used to quantify the drug in its marketed tablet formulation with good recoveries, suggesting their applicability to routine analysis of the drug in bulk as well as in formulation. [ABSTRACT FROM AUTHOR]

Natural antioxidants have attracted attention for their therapeutic use as photochemopreventive agents. Inga edulis leaves extract and its purified fraction have high polyphenolic content and high antioxidant capacity. In addition, they presented UV photostability and low citotoxicity in fibroblast cells. In this context, this study first aimed at development of topical formulation containing purified fraction of I. edulis extract and the evaluation of skin penetration of the compounds. Moreover, the photoprotective/photochemopreventive potential of the formulation containing I. edulis purified fraction were investigated in vitro and in vivo. The topical formulation containing 1% of the purified fraction of I. edulis increased the endogenous antioxidant potential of the skin, and vicenin-2 and myricetin compounds were able to penetrate the epidermis and dermis. Additionally, the purified fraction (25 and 50 mg/mL) showed a photoprotective effect against UVA and UVB radiation in L929 fibroblast cells. In vivo studies have shown that the formulation added with purified fraction provided an anti-inflammatory effect on the skin of animals after UVB exposure, since it was observed a reduction in MPO activity, IL-1β and TNF-α cytokines, and CXCL1/KC chemokine concentrations. In conclusion, the purified fraction of I. edulis, rich in phenolic compounds, when incorporated in topical formulation, appears as an alternative to prevent skin damages induced by UV radiation, due to its antioxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Purpose: The goal of the present investigation was to establish felodipine (FDP) solid dispersion-loaded transmucosal buccal films which may help to increase its solubility and avoid hepatic first-pass metabolism to boost its oral bioavailability leading to better treatment of hypertension. Methods: The solid dispersion was prepared using fusion method. The effect of varying ratios of poloxamer 407 on dissolution of FDP was studied. Prepared FDP solid dispersions were characterized concerning FTIR, DSC, PXRD, and SEM. Further, the standardized FDP solid dispersion was incorporated into RDOFs that were fabricated by mold casting technique. Results: SEM micrographs of RDOFs revealed the presence of FDP solid dispersion in the matrix of the polymer. Ex vivo permeation of the drug from FDP-loaded RDOF and FDP solid dispersion-loaded RDOF across porcine buccal mucosa was found to be 17.3 ± 0.11% and 84.81 ± 7.19%, respectively in 90 min. Conclusion: Obtained results conclude that the prepared FDP solid dispersion-loaded RDOFs may be a useful approach to augment the oral bioavailability of FDP by ameliorating its solubility and the rate of dissolution, and it can also reduce hepatic first-pass metabolism. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study is to modify the release profile of oxcarbazepine by formulating it as a bilayer tablet using direct compression method with dual compression. Methods: In the bilayer system, the immediate release layer was formulated using four types of disintegrants, sodium starch glycolate (SSG), croscarmellose sodium (CCS), cross-linked polyvinylpyrrollidone (crospovidone), and starch. It was found that immediate release layer containing sodium starch glycolate gave faster disintegration time. Therefore, sodium starch glycolate was utilized in the preparation of bilayer tablets in this study. The sustained release layer was prepared utilizing three hydrophobic polymers, two of them are acrylics (Eudragit RS®, Eudragit RL®) and the third one is ethyl cellulose. The prepared bilayer tablets were evaluated for hardness, friability, weight variation, content uniformity, and dissolution profile. Results: The results showed that combination of Eudragit RL® with Eudragit RS® in ratio of 2:1 gave the best modified release profile. Also, using di calcium phosphate as a binder and microcrystalline cellulose (Avicel PH 101) as a diluent resulted in a slower release profile comparing with other formulas. Based on the ʄ2 similarity factor value comparing with reference standard curve, F15, which contains Eudragit RL® and RS® in ratio of 2:1 with mannitol as a diluent and Avicel 102 as a binder, was selected as the best optimized formula. Drug release followed diffusion mechanism rather than erosion mechanism. Furthermore, FTIR spectra showed no possibility of chemical interaction between the drug and polymers, which were used in preparation of bilayer tablet. Stability studies of bilayer tablets under accelerated conditions indicated that the shelf life of the prepared tablets was 3 years and 5 months at 25 °C. However, stability of optimized formula in day light at room temperature revealed that the shelf life of oxcarbazepine is 1 year and 9 months. Conclusion: The results of this study clearly demonstrate that oxcarbazepine can be successfully prepared as a bilayer modified release tablet. [ABSTRACT FROM AUTHOR]

The oncolytic rodent protoparvovirus H-1PV has been successfully used in phase I/II clinical trials to treat recurrent glioblastoma multiforme and pancreatic cancer. The present work focuses on the stability and environmental safety of the H-1PV drug product from production up to its use in patients. We identified hold-steps in manufacturing for up to 3 months and showed 7-years stability for the optimal product formulation. Stress testing via UV, temperature, and pH also determined that the drug product is stable. De- and rehydration for lyophilization simulation are possible without infectious virus loss. Furthermore, we prove in-use stability for 4 days at room temperature and show no virus adsorption to injection devices, guaranteeing the correct administration dose. Iodixanol in the formulation, resulting in high viscosity, protects H-1PV against UV and some disinfectants. Nonetheless, H-1PV is depleted with rapid heat deactivation, autoclavation, and nanofiltration. Assessment of chemical disinfectants that are currently recommended by the Robert Koch-Institute demonstrated that ethanol-based hand disinfectants are not effective; however, aldehyde-based disinfectants for surfaces and instruments demonstrate sufficient H-1PV deactivation in aqueous formulations by 4 to 6 log10. With these results, we could establish a specific hygiene plan for all involved facilities from manufacturing to patient application. Overall, using 48% Iodixanol in Visipaque/Ringer as a drug formulation stabilizes H-1PV infectivity over years and protects against virus loss from short-term UV, low pH, and temperature exposure. Key points: • Optimal formulation of drug product protects the H-1PV protoparvovirus against UV, temperatures up to 50 °C, and low pH (> 1.25), stabilizing the virus during manufacturing, storage, transport, and application. • H-1PV is stable during in-use and does not adsorb to injection devices during patient administration. • Hygiene plan for H-1PV with physicochemical methods has been established. [ABSTRACT FROM AUTHOR]

The development of formulations adapted to the patient's age is a challenge in the pharmaceutical industry. Pediatric and geriatric patients may have difficulties in swallowing oral medications when an adequate formulation is not available. Carvedilol is a poorly water-soluble drug used to treat cardiovascular problems; it is commercialized in several countries only as solid oral formulations, which are often manipulated at the point of administration to treat pediatric or geriatric patients. The purpose of this work was to obtain a new dosage form of Carvedilol using safe excipients, suitable for administration to pediatric and geriatric patients. To improve the solubility of Carvedilol, the effect of several factors was analyzed and optimized. Subsequently, to improve the physical stability of the formulations, two preparation methods were analyzed by adding HPMC. In "method 1," HPMC was dissolved in buffer and incorporated into a mixture of Carvedilol-PEG 400, while in "method 2," Carvedilol was solubilized in buffer containing PEG 400, and then, HPMC was added. Finally, microbiological tests were performed to the stable formulations. The factors "pH value" and "concentration of PEG" affected the solubility of Carvedilol. A formulation containing Carvedilol (3 mg/mL), pH=3, PEG 400 (15% v/v), and HPMC (0.25% w/v) prepared by method 2 was stable for 180 days at 4 °C while those containing Carvedilol (5 mg/mL), pH=3, PEG 400 (27% v/v), and HPMC (0.5% w/v), prepared by method 2, were stable for 180 days at 4 and 25°C. These oral liquid formulations were physicochemical and microbiologically stable for 6 months. [ABSTRACT FROM AUTHOR]

An unknown impurity was detected in in-house prepared ephedrine hydrochloride (HCl) 5 mg/mL prefilled sterilized syringes when applying a stability-indicating British Pharmacopoeia 2018 impurity method for ephedrine injection. Ultraviolet, chromatographic, mass spectral, and physicochemical methods were combined to identify the unknown impurity. The unknown impurity was identified as methcathinone, which is generated from ephedrine drug substance through an oxidation reaction. A formulation study, in which different process adjustments were tested, was carried out to reduce the amount of unknown impurity. Nitrogen gassing in combination with 0.05 M citrate buffer addition proved to be the most potent process adjustment in reducing methcathinone formation in ephedrine HCl 5 mg/mL prefilled sterilized syringes after 4 months of storage in the dark at room temperature (20 °C ± 5 °C). More detailed research on the long-term stability of the reformulated ephedrine HCl drug product is currently underway, with promising results for up to 9 months gathered already. [ABSTRACT FROM AUTHOR]

Polyvinyl alcohol (PVA) is a biodegradable, water-soluble polymer with excellent film forming properties, commonly studied or used as tablet coating, food packaging or controlled release fertilizers. Attract-and-kill (AK) beads are sustainable, microbial alternatives to synthetic soil insecticides, whose onset of lethal effect largely depend on how fast the encapsulated entomopathogenic fungus forms virulent conidia. Therefore, the objective of this study was to develop a water-soluble coating accelerating the kill effect of AK beads by immediately releasing virulent Metarhizium brunneum CB15-III blastospores. We assessed three PVA types (PVA 4-88, 8-88, 10-98) which differed in their degree of hydrolysis or molecular weight for their ability to release viable blastospores from thin films after drying at 60–40 °C, and examined how polyethylene glycol and soy-lecithin impact the blastospore survival. Finally, we evaluated the effectiveness of coated AK beads in a bioassay against Tenebrio molitor larvae. The blastospore release rate quadrupled within the first 5 min with decreasing molecular weight and degree of hydrolysis, with PVA 4-88 releasing 79 ± 19% blastospores. Polyethylene glycol and soy-lecithin significantly increased the blastospore survival to 18–28% for all three PVA types. Coated beads exhibited a uniform, 22.4 ± 7.3 µm thin coating layer, with embedded blastospores, as confirmed by scanning electron microscopy. The blastospore coating increased the mortality rate of T. molitor larvae over uncoated AK beads, decreasing the median lethal time from 10 to 6 days. Consequently, the blastospore coating accelerated the kill effect of regular AK beads. These findings pave the way to enhanced pest control efficacy from coated systems such as beads or seeds. Key points: PVA enables immobilization of virulent blastospores on alginate beads. Blastospore coating accelerates kill effect of attract-and-kill beads. PEG4000 and soy lecithin improve blastospore survival in PVA films. [ABSTRACT FROM AUTHOR]

Detergent products are a formulated mixture of ingredients with a washing or cleaning power. The most active compounds involved in the cleaning process are the so-called surfactants; amphiphilic compounds with polar head and an-polar teal. They have the property to lower the surface tension (ST) of water, to adsorb to the interface and to reduce the interfacial tension (IFT) between two immiscible liquid. Then, they are very good at liberating dirt and to eliminate impurities. However, owing their chemical nature, they are characterized by their high toxicity and low biodegradability causing serious risks to natural ecosystems. Therefore, an urgent need was developed for the production of environment friendly detergent. Thus, developing eco-friendly, nonirritant, low-toxic, and high-efficient surface active ingredients for detergents is an ongoing challenge in the detergent field. To know, biosurfactants (BioS) or microbial surfactants are amphiphilic compounds having the ability to reduce the surface and interfacial tension. They are characterized by their higher biodegradability, low toxicity and eco-friendly. Thus, they can be the best substitutes of chemical surfactants in detergent formulation permitting the development of eco-friendly bio-based detergent formula. With this aim, we will discuss in the first part of the presented review detergent formula and surfactants as the base ingredients; their physic-chemical properties and higher toxicity. In the second part of the review paper, BioS as emerging ingredients for detergent formulation will be presented; their classification, physic-chemical and functional properties along with their potential application in detergent formulation. [ABSTRACT FROM AUTHOR]

Minimizing water delivery costs and increasing water supply dependability are the two key objectives in designing and operating of water distribution systems. An analytical solution for the best pipe diameters of a water distribution pipe network was created in this study. The raw water was collected from a water canal and transported to a treatment plant (WTP). The cleansed water was pushed into the water distribution network via the pumping station. The derivative approach was used in the optimization process, and the cost functions incorporating the various capital and operating expenses were used. The initial diameters were adjusted to reach the least-cost diameters. The study shows that the optimum design of a pipe network (PNW) achieves saving a total cost of about 12.3% after utilizing our unique method. The optimal pumping rate in the PNW can also be determined using an analytical approach that considers the optimum value that occurs when the minor and friction losses in the entire network are at their lowest. The analytical solution for the optimum pumping rate shows a rigid value of optimum pumping rate (Qopt) which is 5296.32 m3/day. On comparative estimates, this figure is very close to that of 5,300 m3/day interpreted from the graphical solution, with negligible deviation. The total cost and optimum pumping rate results for the analyzed PNW example demonstrate the correctness of the analytical solutions, reliability, and dependability of the assumptions. [ABSTRACT FROM AUTHOR]

The present review summarizes the use of differential scanning calorimetry (DSC) and scattering techniques in the context of protein formulation design and characterization. The scattering techniques include wide angle X-ray diffractometry (XRD), small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS). While DSC is valuable for understanding thermal behavior of the excipients, XRD provides critical information about physical state of solutes during freezing, annealing and in the final lyophile. However, as these techniques lack the sensitivity to detect biomolecule-related transitions, complementary characterization techniques such as small-angle scattering can provide valuable insights. [ABSTRACT FROM AUTHOR]

Purpose: Inherent structural and functional properties of biotechnology-derived therapeutic biologics make them susceptible to light- and temperature-induced degradation and consequently can influence their quality. Photosensitivity of therapeutic proteins continues to be examined, but the commonalities and trends of storage conditions and information about light and temperature sensitivity among currently licensed therapeutic proteins has not been previously surveyed. Methods: Using a comprehensive and relational database approach, we conducted a scientific survey of all licensed biotechnology-derived drug products with the goal of providing evidence-based information about recommended storage conditions of formulations sorted by light- and temperature-related attributes as described for each product at licensure. Results: We report the prevalence of indications for light and temperature sensitivity in formulations categorized by their presentation type, number of doses, container type, dosage form and active molecule type. We also report the storage temperature range across formulations and diluents for reconstitution and dilution. Formulations with excipients that potentially facilitate light-induced and thermal degradation were also noted. Conclusions: The result of our analysis indicates that light and temperature sensitivity are prevalent across therapeutic protein formulations. However, when a formulation is reconstituted or diluted, both light and temperature sensitivity are less clear. In addition, light and temperature sensitivity are more well defined in liquid formulations than lyophilized powder formulations, and more well defined in products manufactured in autoinjectors, prefilled-syringes, and pens than products in vials. Overall, our report provides a data-driven summary of storage conditions among therapeutic protein formulations to support the development of future biologic drug products. [ABSTRACT FROM AUTHOR]