Formulation Components Research Articles

Инновационные формы эссенциального микроэлемента железа для обогащения молочных продуктов

This article introduces a new method for fortification of dairy products. It is based on a synthesis of biologically active complexes of ascorbic acid, trace iron, and such essential amino acids as lysine, phenylalanine, isoleucine, tryptophan, methionine, valine, and threonine. The computer modeling of the complex structure made it possible to define the optimal interaction parameters of the formulation components. The complex of ascorbic acid, iron, and tryptophan demonstrated the most potent antioxidant activity.

Advanced analysis of disintegrating pharmaceutical compacts using deep learning-based segmentation of time-resolved micro-tomography images

The mechanism governing pharmaceutical tablet disintegration is far from fully understood. Despite the importance of controlling a formulation's disintegration process to maximize the active pharmaceutical ingredient's bioavailability and ensure predictable and consistent release profiles, the current understanding of the process is based on indirect or superficial measurements. Formulation science could, therefore, additionally deepen the understanding of the fundamental physical principles governing disintegration based on direct observations of the process. We aim to help bridge the gap by generating a series of time-resolved X-ray micro-computed tomography (μCT) images capturing volumetric images of a broad range of mini-tablet formulations undergoing disintegration. Automated image segmentation was a prerequisite to overcoming the challenges of analyzing multiple time series of heterogeneous tomographic images at high magnification. We devised and trained a convolutional neural network (CNN) based on the U-Net architecture for autonomous, rapid, and consistent image segmentation. We created our own μCT data reconstruction pipeline and parameterized it to deliver image quality optimal for our CNN-based segmentation. Our approach enabled us to visualize the internal microstructures of the tablets during disintegration and to extract parameters of disintegration kinetics from the time-resolved data. We determine by factor analysis the influence of the different formulation components on the disintegration process in terms of both qualitative and quantitative experimental responses. We relate our findings to known formulation component properties and established experimental results. Our direct imaging approach, enabled by deep learning-based image processing, delivers new insights into the disintegration mechanism of pharmaceutical tablets.

Optimization of Pramipexole-Loaded In Situ Thermosensitive Intranasal Gel for Parkinson's Disease.

The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson's disease. Preliminary studies were performed to select formulation components and identify key variables affecting the formulation. The optimization of the in situ gelling system of Pramipexole dihydrochloride was achieved by applying 32 full factorial design using Design-Expert® software (Stat-Ease 9.0.6 version) and taking concentrations of Poloxamer 407 (X1) and HPMC K4M (X2) as independent variables. The gelling temperature, gel strength, and percentage of drug diffused after 8 h were taken as dependent variables. The software provided an optimized formulation, with 16.50% of X1 and 0.2% of X2 with the highest desirability. An in vivo drug retention time study was performed for the optimized formulation in Wistar rats. The results of the optimization process demonstrated that the selected gel formulation exhibited desirable characteristics, including gelation near body temperature, good gel strength, suitable viscosity, and sustained drug release. The optimized formulation displayed significantly higher drug retention, lasting about 5 h, versus the plain poloxamer gel formulation. Hence, it was concluded that the optimized formulation will remain affixed at the site of application for a significant time after intranasal administration and consequently sustain the release of the drug. The optimized formulation was found to be stable during the stability studies. The developed dosage form may improve patient compliance, enhance nasal drug residence, and offer sustained drug release. However, further clinical studies are necessary to validate these findings.

Mechanistic investigation of quercetin in the management of diabetic foot ulcer by network pharmacology and molecular docking

BackgroundQuercetin (QUE), being a strong antioxidant, has been a part of Chinese traditional medicine for ages for the management of a large number of ailments including type 2 diabetes mellitus and its complications, primarily, Diabetic Foot Ulcer (DFU), but it is under lying mechanisms remain elusive. The introduction of network pharmacology and molecular docking has made it facile to investigate the mechanism of QUE-containing different plants and to validate the binding affinity of QUE with DFU protein respectively. AimThis study is aimed to investigate the mechanism of QUE in protecting against DFU through modern approaches viz. network pharmacology and molecular docking. Materials and methodsThe traditional Chinese medicine system pharmacology analysis platform (TCMSP) has been used to retrieve the active ingredients in various Chinese formulations. QUE was found to be a bioactive component of various Chinese formulations. The core therapeutic targets of QUE against DFU were identified using a protein–protein interaction (PPI) network. QUE-associated targets and genes related to DFU were obtained from different comprehensive databases (Pubchem, Swiss target prediction database, SEA database, String database, DisGeNET database, Molegro virtual docker version 6.0, ADMET lab2.0, SwissADME database) were intersected, and analyzed to obtain mapping targets and ranked to obtain key targets. ResultsThe Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway shows major pathways were obtained from for QUE was matrix metallopeptidase 9 (MMP9). Receptor-ligand interaction between QUE with MMP9 were evaluated via MVD 6.0 software. A total of 10 interactions of quercetin with the following moldock score, rerank score, and H-bond interactions were observed as -110.912, -37.33, and -12.11 respectively. Candidate targets MMP9 in diabetic complications were ascertained and found associated with QUE against the management of DFU. Molecular docking models showed that QUE could closely bind to the key targets MMP9 (PDB id: 2OVX). ADME/T Analysis is performed to check the pharmacokinetic and toxicity profile which complies with the ideal values. ConclusionsThis study proposed MMP9, as the key target of bioactive QUE in mechanistic control of DFU by lowering the activity of the IL-17 signalling pathway, Leukocyte trans-endothelial migration, Fluid shear stress, and atherosclerosis respectively. Future aspectsThe explication of mode of action of bioactive constituent QUE against DFU provide a theoretical basis for designing more promising agents further for treatment of DFU in diabetic patients.

Solid Lipid Nanoparticles as an Innovative Lipidic Drug Delivery System.

In order to overcome some of the drawbacks of traditional formulations, increasing emphasis has recently been paid to lipid-based drug delivery systems. Solid lipid nanoparticles (SLNs) are among these delivery methods, and they hold promise because of their simplicity in production, capacity to scale up, biocompatibility, and biodegradability of formulation components. Other benefits could be connected to a particular route of administration or the makeup of the ingredients being placed into these delivery systems. This article aims to review the significance of solid lipid nanocarriers, their benefits and drawbacks, as well as their types, compositions, methods of preparation, mechanisms of drug release, characterization, routes of administration, and applications in a variety of delivery systems with a focus on their efficacy.

Re-N-acetylation of group B Streptococcus type Ia capsular polysaccharide improves the immunogenicity of glycoconjugate vaccines

The capsular polysaccharides (CPS) of Group B Streptococcus play a crucial role as virulence determinants and are potential candidates for antigenic components in vaccine formulations. Alkaline treatments are commonly used to extract polysaccharides owing to their efficiency and cost-effectiveness; however, they may induce the removal of N-acetyl groups from CPS. This study involved re-N-acetylation of CPS Ia to improve its biological functionality. The structural modifications and enhanced antigenicity of CPS Ia were observed after re-N-acetylation. The tetanus toxoid (TT) was conjugated with either partially de-N-acetylated or fully re-N-acetylated CPS. As a result, the conjugate containing re-N-acetylated CPS (IaReN-TT) enhanced the induction of IgG antibody levels and functional antibodies in mice. Both passive and active protection assays substantiated the superior protective efficacy of IaReN-TT, suggesting that the re-N-acetylation of CPS Ia could be a critical step in refining the immunogenic profile of glycoconjugate vaccines.

The key components of a clinical psychology formulation: A consensus study.

Psychological formulation is a key competency for clinical psychologists. However, there is a lack of consensus regarding the key components and processes of formulation that are hypothesized to contribute to poor reliability of formulations. The aim of this study was to develop consensus on the essential components of a formulation to inform training for clinical psychologists and best practice guidelines. A Delphi methodology was used. Items were generated from the literature and discussed and refined with a panel of experts (n = 10). In round one, 110 clinical psychologists in the United Kingdom rated the importance of components of formulation via an online questionnaire. Criteria for consensus were applied and statements were rerated in round two if consensus was not achieved. Consensus was achieved on 30 items, with 18 statements regarding components of a formulation and 12 statements regarding formulation process. Items that clinicians agreed upon emphasized the importance of integrating sociocultural, biological, strengths and personal meaning alongside well-established theoretical frameworks. Consensus was not reached on 20 items, including whether a formulation should be parsimonious or adhere to a model. Our findings provide mixed evidence regarding consensus on the key components of formulation. There was an agreement that formulation should be client-led and incorporate strengths and sociocultural factors. Further research should explore client perspectives on the key components of formulation and how these compare to the clinicians' perspectives.

The use of evidence-based programmes in family support across Europe: A comparative survey study

The importance of using evidence-based programmes to ensure children’s rights and families’ wellbeing is increasingly recognized in Europe. However, there are few and partial attempts to gain insight into the scope of prevention and promotion programmes currently implemented in child and family services across Europe, often located outside the formal peer-reviewed channels. The objectives of this study are empirically examining the diversity of family support programmes delivered and the extent to which they meet evidence-based standards for programme formulation and provide a picture of the typologies according to programme descriptors, operational aspects and implementation components. The Family Support Programmes' Survey was used to identify existing programmes addressing family support in participating countries. The sample includes 193 support programmes from 17 European countries, members of the European Family Support Network corresponding to three regions of Europe (Northern, Southern and Central-Eastern). The comparative survey was conducted using the Data Collection Sheet to gather information about program characteristics. Descriptive and cluster analyses were carried out. Results show that a large number of programmes fulfil evidence-based standards for programme formulation, such as clearly defined theoretical framework, manualization, and methodology components. In addition, three cluster profiles of programme formulation components were determined corresponding to the three European regions. Implications for research and practice on the development of family support programmes according to evidence-based standards for programme formulation are discussed.

Bio-based epoxidized soybean oil branched cardanol ethers as compatibilizers of polybutylene succinate (PBS)/polyglycolic acid (PGA) blends

Blending poly(butylene succinate) (PBS) with another biodegradable polymer, polyglycolic acid (PGA), has been demonstrated to improve the barrier performance of PBS. However, blending these two polymers poses a challenge because of their incompatibility and large difference of their melting temperatures. In this study, we synthesized epoxidized soybean oil branched cardanol ether (ESOn-ECD), a bio-based and environmentally friendly compatibilizer, and used it to enhance the compatibility of PBS/PGA blends. It was demonstrated that the terminal carboxyl/hydroxyl groups of PBS and PGA can react with ESOn-ECD in situ, leading to branching and chain extension of PBS and PGA. The addition of ESO3-ECD to the blend considerably diminished the dispersed phase of PGA. Specifically, in comparison to the PBS/PGA blend without a compatibilizer, the diameter of the PGA phase decreased from 2.04 μm to 0.45 μm after the addition of 0.7 phr of ESO3-ECD, and the boundary between the two phases became difficult to distinguish. Additionally, the mechanical properties of the blends were improved after addition of ESO3-ECD. This research expands the potential applications of these materials and promotes the use of bio-based components in blend formulations.

Mechanistic Insights into the Adsorption of Monoclonal Antibodies at the Water/Vapor Interface.

Monoclonal antibodies (mAbs) are active components of therapeutic formulations that interact with the water-vapor interface during manufacturing, storage, and administration. Surface adsorption has been demonstrated to mediate antibody aggregation, which leads to a loss of therapeutic efficacy. Controlling mAb adsorption at interfaces requires a deep understanding of the microscopic processes that lead to adsorption and identification of the protein regions that drive mAb surface activity. Here, we report all-atom molecular dynamics (MD) simulations of the adsorption behavior of a full IgG1-type antibody at the water/vapor interface. We demonstrate that small local changes in the protein structure play a crucial role in promoting adsorption. Also, interfacial adsorption triggers structural changes in the antibody, potentially contributing to the further enhancement of surface activity. Moreover, we identify key amino acid sequences that determine the adsorption of antibodies at the water-air interface and outline strategies to control the surface activity of these important therapeutic proteins.

The effect of linseed oil/canola oil blend on the coating and thermal properties of waste PET-based alkyd resins.

This study aims to prepare oil-modified alkyd resins using a linseed oil/canola oil (LO/CO) blend and waste PET depolymerization product, suitable for environmentally friendly coating applications. Waste PET flakes obtained from grinding post-consumer water bottles were depolymerized by the aminoglycolysis reaction at high pressure. Raw depolymerization product (DP) was used in the synthesis of four components, 50% oil alkyd resins by monoglyceride method. DP has partly replaced the dibasic acid component in the PET-based alkyd formulations. Besides PET-based alkyds, reference alkyds without DP were also synthesized for comparison. Then, the surface coating properties and thermal behaviors of alkyd films were determined. The effect of DP usage and the changing ratios of LO/CO blend on coating properties and thermal behaviors of alkyd films were investigated. In addition, the optimum LO/CO blend ratio which is compatible with alkyd formulation was attempted to be determined. At the end of this study, glossy, soft/medium-hard films were obtained with excellent adhesion, impact strength, and chemical resistance. Thermal resistance and final thermal oxidative degradation temperature increased with adding DP to the alkyd formulation. Using LO/CO blend in the formulations affected oxidation rate and ratio, hence, drying time/degree and oxidative stability of alkyd films.

Ionic liquid-coated lipid nanoparticles increase siRNA uptake into CNS targets.

Lipidoid nanoparticles (LNPs) have transformed the field of drug delivery and are clinically used for the delivery of nucleic acids to liver and muscle targets. Post-intravenous administration, LNPs are naturally directed to the liver due to the adsorption of plasma proteins like apolipoprotein E. In the present work, we have re-engineered LNPs with ionic liquids (ILs) to reduce plasma protein adsorption and potentially increase the accumulation of LNPs in hard-to-deliver central nervous system (CNS) targets such as brain endothelial cells (BECs) and neurons. We have developed two approaches to re-engineer LNPs using a choline trans-2-hexenoate IL: first, we have optimized an IL-coating process using the standard LNP formulation and in the second approach, we have incorporated ILs into the LNPs by replacing the PEG-lipid component in the standard formulation using ILs. IL-coated as well as IL-incorporated LNPs were colloidally stable with morphologies similar to the standard LNPs. IL-coated LNPs showed superior uptake into mouse BECs and neurons and demonstrated reduced mouse plasma protein adsorption compared to the standard LNPs. Overall, our results (1) demonstrate the feasibility of re-engineering the clinically approved LNP platform with highly tunable biomaterials like ILs for the delivery of therapeutics to CNS targets like BECs and neurons and (2) suggest that the surface properties of LNPs play a critical role in altering their affinity to and uptake into hard-to-deliver cell types.

Decoding Success: Assessing the Online Pseudocode Interpreter through Users Insights

Pseudocode is vital in enhancing programming comprehension, making it an essential component of the Programming Logic Formulation (CS1) course. However, many CS1 students from various senior high school strands struggle with this concept, highlighting the need for additional learning resources. This research evaluated a pseudocode interpreter designed for first-year Information and Communications Technology (ICT) students at Iloilo Science and Technology University in Iloilo City, Philippines. Using random sampling, 147 first-year ICT students were selected to evaluate the software's user experience in usability, credibility, appearance, and loyalty using the Standardized User Experience Percentile Rank Questionnaire (SUPR-Q). Likewise, five ICT experts were selected using purposive sampling to evaluate the system's validity as instructional material based on its content and on the material's organization, form, and style using the university's Quality Form for Instructional Materials (IM). The user experience evaluation yielded positive results, with students unanimously agreeing on the software's ease of use, dependability, and user-friendliness. The expert evaluation confirmed the system's validity as instructional material, commending its content, organization, form, and style. These findings suggest that the pseudocode interpreter provides immediate benefits for students, offering a valuable learning tool. Moreover, the software has the potential to be adopted by other faculty members, promoting a more efficient and captivating learning experience. Future research could investigate how interpreters affect student learning and their usefulness in various educational settings.

The taste for health: the role of taste receptors and their ligands in the complex food/health relationship.

Taste, food, and health are terms that have since always accompanied the act of eating, but the association was simple: taste serves to classify a food as good or bad and therefore influences food choices, which determine the nutritional status and therefore health. The identification of taste receptors, particularly, the G protein-coupled receptors that mediate sweet, umami, and bitter tastes, in the gastrointestinal tract has assigned them much more relevant tasks, from nutrient sensing and hormone release to microbiota composition and immune response and finally to a rationale for the gut-brain axis. Particularly interesting are bitter taste receptors since most of the times they do not mediate macronutrients (energy). The relevant roles of bitter taste receptors in the gut indicate that they could become new drug targets and their ligands new medications or components in nutraceutical formulations. Traditional knowledge from different cultures reported that bitterness intensity was an indicator for distinguishing plants used as food from those used as medicine, and many non-cultivated plants were used to control glucose level and treat diabetes, modulate hunger, and heal gastrointestinal disorders caused by pathogens and parasites. This concept represents a means for the scientific integration of ancient wisdom with advanced medicine, constituting a possible boost for more sustainable food and functional food innovation and design.

Cement retarding mechanism of phosphonates and their interaction with aluminium

Phosphonates show a broad variety of structures. This work shows the correlation of molecular structure and performance in cement.

Investigation of the Molecular Interactions of Vaccine Adjuvants: Can a Strategic Trio of Toll-like Receptor Agonists Enhance Efficacy in a Multifaceted Approach?

Background: The imperative need for effective vaccines against viral diseases has intensified research on adjuvants to enhance immune responses. Toll-like receptor (TLR) agonists, such as Imiquimod, Resiquimod, and CpG oligodeoxynucleotides (CpG ODN), are some crucial components in vaccine formulations. This study investigated the molecular interactions and binding affinities of TLR4, TLR7/8, and TLR9 agonists, through in silico techniques. Methods: The three-dimensional structure of human TLR9 was predicted using Iterative Threading ASSEmbly Refinement. Homology modeling was employed using a multi-step approach to generate the human TLR9 model including template identification, ab initio modeling, iterative refinement, and final model generation of the crystallographic structure. Molecular docking and simulation studies were performed using AutoDock Vina, HDOCK, and GROningen MAchine for Chemical Simulations tools. The molecular docking study revealed binding sites and binding affinities of adjuvants in the binding regions of target TLRs. Molecular dynamics simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area calculations ascertain the stability and binding energies of the TLR-adjuvant complexes. Results: Results indicate distinct interactions, with Resiquimod showing superior affinity toward TLR7. QS21, on the other hand, emerged as a potent TLR4 agonist, while CpG ODN 2006 binds specifically to TLR9. The study proposes a strategic combination of QS21, Resiquimod, and CpG ODN 2006 as a potential adjuvant system, offering a multifaceted approach to enhance vaccine efficacy. Conclusions: This study furnishes preliminary data and establishes the foundational framework for subsequent inquiries encompassing both in vitro and in vivo studies concerning vaccine adjuvant systems.

Harnessing AI for Optimizing Formulation Components in Advanced Drug Delivery Systems: Analysis of Large-Scale Screening Data

Harnessing AI for Optimizing Formulation Components in Advanced Drug Delivery Systems: Analysis of Large-Scale Screening Data

Navigating the challenges of lipid nanoparticle formulation: the role of unpegylated lipid surfactants in enhancing drug loading and stability.

Lipid nanoparticles have proved an attractive approach for drug delivery; however, the challenges of optimising formulation stability and increasing drug loading have limited progression. In this work, we investigate the role of unpegylated lipid surfactants (helper lipids) in nanoparticle formation and the effect of blending helper lipids with pegylated lipid surfactants on the formation and stability of lipid-based nanoparticles by nanoprecipitation. Furthermore, blends of unpegylated/pegylated lipid surfactants were examined for ability to accommodate higher drug loading formulations by means of a higher weight percentage (wt%) of drug relative to total mass of formulation components (i.e. drug, surfactants and lipids). Characterisation included evaluation of particle diameter, size distribution, drug loading and nanoformulation stability. Our findings demonstrate that the addition of unpegylated lipid surfactant (Lipoid S100) to pegylated lipid surfactant (Brij S20) enhances stability, particularly at higher weight percentages of the core material. This blending approach enables drug loading capacities exceeding 10% in the lipid nanoparticles. Notably, Lipoid S100 exhibited nucleating properties that aided in the formation and stabilisation of the nanoparticles. Furthermore, we examined the incorporation of a model drug into the lipid nanoparticle formulations. Blending the model drug with the core material disrupted the crystallinity of the core, offering additional potential benefits in terms of drug release and stability. This comprehensive investigation provides valuable insights into the interplay between surfactant properties, core material composition, and nanoparticle behaviour. The study enhances our understanding of lipid materials and offers guidance for the design and optimisation of lipid nanoparticle formulations.

Critical Analysis of Surfactant-Dye Interaction: A Review

The interaction between surfactants and dyes is fundamental in achieving the desired coloration and properties in various applications, shaping the functionality and effectiveness of dye-related processes across multiple industries. Further research and advancements in this field will continue contributing to innovative solutions and improved sustainability. While mixed surfactants offer these advantages, the choice between using a single surfactant or a mixture depends on the specific application, the desired properties, cost considerations, and compatibility with other formulation components. It's important to carefully evaluate the application requirements and conduct appropriate testing to determine the most effective approach. In this work, the physical-chemical characteristics and solubilization of reactive dyes in single and mixed micellar media are elaborated. Compared to the single-micellar medium, the mixed-micellar medium showed improved reactive dye trapping, which was attributed to the presence of both cationic and nonionic surfactants, namely cetyltrimethylammonium bromide (CTAB) and triton X-100. In this interactional study, two reactive dyes were used: Reactive Black 5 (RB) and Reactive Yellow 145 (RY). It is noteworthy to examine the modeling and micellization of mixed surfactant systems in an aqueous medium including dodecyl trimethylammonium bromide (DTAB) and sodium dodecyl sulfate (SDS). The anionic-rich and cationic-rich interactions between methylene blue (MB) and methyl orange (MO) in aqueous solutions were clearly shown in the diagram.

A consistent multi-phase-field formulation for anisotropic brittle fracture

Anisotropic fracture modelling constitutes an important problem in fracture mechanics as many natural, composite and architected materials exhibit fracture anisotropy. The multi-phase-field technique offers a seemingly straightforward and easy-to-implement approach for handling a range of fracture anisotropies, some of which would otherwise necessitate the use of higher-order damage formulation. However, a closer examination reveals that the formulation contains a few inconsistencies, which hinder the establishment of precise definitions for crack through phase-fields and fracture toughness. In this article, we present modifications to the multi-phase-field approach aimed at rectifying these issues. Our model introduces a new degradation function, enabling an unambiguous definition of crack and leading to an analytical expression of the modelled fracture toughness. We conduct an in-depth analysis of several key components of the present formulation and discuss the nature of anisotropy it can handle in its current form, and also outline a roadmap for expanding its capability. A limited set of numerical simulations is also provided to illustrate the effectiveness of the current proposition.