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Materials (Basel, Switzerland) May 2024Knowledge about the thermodynamic equilibria of the PO-NaO and PO-MgO systems is very important for controlling the phosphorus content of steel materials in the process...
Knowledge about the thermodynamic equilibria of the PO-NaO and PO-MgO systems is very important for controlling the phosphorus content of steel materials in the process of steelmaking dephosphorization. The phase equilibrium and thermodynamic data of the PO-NaO and PO-MgO systems were critically evaluated and re-assessed by the CALPHAD (CAlculation of PHAse Diagram) approach. The liquid phase was described by the ionic two-sublattice model for the first time with the formulas (Na)(O, PO, PO, PO) and (Mg)(O, PO, PO, PO), respectively, and the selection of the species constituting the liquid phase was based on the structure of the phosphate melts. A new and improved self-consistent set of thermodynamic parameters for the PO-NaO and PO-MgO systems was finally obtained, and the calculated phase diagram and thermodynamic properties exhibited excellent agreement with the experimental data. The difference in the phase composition of invariant reactions from the experimentally determined values reported in the literature is less than 0.9 mol.%. The present thermodynamic modeling contributes to constructing a multicomponent oxide thermodynamic database in the process of steelmaking dephosphorization.
PubMed: 38793288
DOI: 10.3390/ma17102221 -
Molecules (Basel, Switzerland) May 2024, as a globally prevalent evergreen tree, contains a wealth of bioactive components that play a crucial role in the pharmaceutical field. extracts, defined as a... (Review)
Review
, as a globally prevalent evergreen tree, contains a wealth of bioactive components that play a crucial role in the pharmaceutical field. extracts, defined as a collection of one or more bioactive compounds extracted from the genus spp., have become a significant focus of modern cancer treatment research. This review article aims to delve into the scientific background of extracts and their considerable value in pharmaceutical research. It meticulously sifts through and compares various advanced extraction techniques such as supercritical extraction, ultrasound extraction, microwave-assisted extraction, solid-phase extraction, high-pressure pulsed electric field extraction, and enzymatic extraction, assessing each technology's advantages and limitations across dimensions such as extraction efficiency, extraction purity, economic cost, operational time, and environmental impact, with comprehensive analysis results presented in table form. In the area of drug formulation design, this paper systematically discusses the development strategies for solid, liquid, and semi-solid dosage forms based on the unique physicochemical properties of extracts, their intended medical uses, and specific release characteristics, delving deeply into the selection of excipients and the critical technical issues in the drug preparation process. Moreover, the article looks forward to the potential directions of extracts in future research and medical applications, emphasizing the urgency and importance of continuously optimizing extraction methods and formulation design to enhance treatment efficacy, reduce production costs, and decrease environmental burdens. It provides a comprehensive set of preparation techniques and formulation optimization schemes for researchers in cancer treatment and other medical fields, promoting the application and development of extracts in pharmaceutical sciences.
Topics: Taxus; Plant Extracts; Humans; Drug Compounding; Solid Phase Extraction
PubMed: 38792152
DOI: 10.3390/molecules29102291 -
International Journal of Molecular... May 2024The modified release of active substances such as chlorzoxazone from matrix tablets, based on KollidonSR and chitosan, depends both on the drug solubility in the...
The modified release of active substances such as chlorzoxazone from matrix tablets, based on KollidonSR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on KollidonSR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % KollidonSR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil 1 w/w %, magnesium stearate 0.5 w/w % and Avicel up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both KollidonSR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.
Topics: Tablets; Chlorzoxazone; Delayed-Action Preparations; Chitosan; Hydrophobic and Hydrophilic Interactions; Drug Liberation; Solubility; Excipients; Chemistry, Pharmaceutical
PubMed: 38791175
DOI: 10.3390/ijms25105137 -
European Journal of Pharmaceutics and... Jul 2024Ionizable lipids are a class of pharmaceutical excipients with a main application in lipid nanoparticles for nucleic acid delivery. New ionizable lipids are needed to...
Ionizable lipids are a class of pharmaceutical excipients with a main application in lipid nanoparticles for nucleic acid delivery. New ionizable lipids are needed to tune characteristics of lipid-based nucleic acid delivery systems, e.g. stability, nucleic acid loading capacity and binding strength, as well as bio-distribution. Herein, we present the synthesis of three novel ionizable lipids as putative excipients for lipid-based nucleic acid delivery systems. Langmuir monolayer experiments with classical surface pressure/area isotherm evaluation were used to understand the self-assembly behavior of the lipids. Additional experiments with surface sensitive techniques, namely grazing incidence x-ray scattering and infrared reflection-absorption spectroscopy (IRRAS), were performed to understand structural characteristics of lipid associates. The latter technique was also used to investigate the nucleic acid binding process between DNA and the ionizable lipids. Finally, first transfection experiments with the novel lipids formulated as cationic liposomes were performed providing first efficacy data. Although the alkyl chain pattern was comparable for all three ionizable lipids, the results demonstrated that with increasing head-group size the DNA binding capacity changed and the alkyl chain fluidity was increased. The lipid with the lowest phase transition temperature and the smallest packing parameter showed the highest DNA transfer efficiency.
Topics: Lipids; Fatty Acids; DNA; Liposomes; Excipients; Nanoparticles; Surface Properties
PubMed: 38789063
DOI: 10.1016/j.ejpb.2024.114338 -
Proceedings of the National Academy of... May 2024Biomolecular condensates are cellular compartments that concentrate biomolecules without an encapsulating membrane. In recent years, significant advances have been made...
Biomolecular condensates are cellular compartments that concentrate biomolecules without an encapsulating membrane. In recent years, significant advances have been made in the understanding of condensates through biochemical reconstitution and microscopic detection of these structures. Quantitative visualization and biochemical assays of biomolecular condensates rely on surface passivation to minimize background and artifacts due to condensate adhesion. However, the challenge of undesired interactions between condensates and glass surfaces, which can alter material properties and impair observational accuracy, remains a critical hurdle. Here, we introduce an efficient, broadly applicable, and simple passivation method employing self-assembly of the surfactant Pluronic F127 (PF127). The method greatly reduces nonspecific binding across a range of condensates systems for both phase-separated droplets and biomolecules in dilute phase. Additionally, by integrating PF127 passivation with the Biotin-NeutrAvidin system, we achieve controlled multipoint attachment of condensates to surfaces. This not only preserves condensate properties but also facilitates long-time fluorescence recovery after photobleaching imaging and high-precision single-molecule analyses. Using this method, we have explored the dynamics of polySIM molecules within polySUMO/polySIM condensates at the single-molecule level. Our observations suggest a potential heterogeneity in the distribution of available polySIM-binding sites within the condensates.
Topics: Biomolecular Condensates; Poloxamer; Biotin; Avidin; Fluorescence Recovery After Photobleaching; Surface Properties; Surface-Active Agents; Single Molecule Imaging
PubMed: 38781207
DOI: 10.1073/pnas.2403013121 -
PloS One 2024The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination...
The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination (Clopidogrel bisulphate and Aspirin) tablets. The proposed combination product utilizes Clopidogrel to protect the moisture-sensitive aspirin component, enhancing its stability against atmospheric conditions. Response-surface approach (Design Expert vs. 13) was used to generate this IR tablet by calculating the right composition of independent variables such as Microcrystalline cellulose 102, pregelatinized starch and Hydroxypropyl cellulose. 32 factorial design was used to estimate the effects of these independent variables on the responses of dependent variables (disintegration & friability) and constructed a total of nine (9) formulations. Pre and Post formulation, quality control parameters were investigated as per pharmacopeia. A systematic approach was used for the optimization process and a prototype checkpoint batch (CPB) based on the better contrast of independent variables was prepared. In vitro analysis of formulations was carried out to estimate the responses. Friability was found in the range of 0.088-1.076%w/w, except F1 = 1.076 all are within limits (NMT 1.0%). Disintegration time was recorded 7.3 ± 1.20 as lower and 24.5 ± 1.63 min was the highest. The release of drugs from their dosage form was fast and rapid, for clopidogrel after 15min was 70.42-96.82% with SD ± 8.71 and aspirin was 69.88-91.49% in 15 min with SD ± 6.41, all the tablets were released more than 80% in 20 min. The stability outcomes of CPB tablets after 15 days of stress study (60 ± 2°C and 75 ± 5%) indicated good compatibility and stability of APIs with excipients. It was concluded that the direct compression method can be preferred to prepare a combination product with cost-effectiveness. It was also concluded that the proposed methodology could increase Aspirin's stability and allow for an aqueous coating system to finish the product with a film coating. By using Design Expert software, the best composition of the formulation can be selected and optimized in a short period of time with minimum trial and errors. The results also demonstrated that the use of a fixed-dose combination tablet instead of the individual is expected to be more convenient to patients and thus improves patient compliance and decreases the occurrence of adverse effects and side effects.
Topics: Clopidogrel; Aspirin; Tablets; Ticlopidine; Drug Combinations; Humans; Platelet Aggregation Inhibitors; Drug Compounding; Chemistry, Pharmaceutical
PubMed: 38781151
DOI: 10.1371/journal.pone.0303705 -
Regenerative Biomaterials 2024The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly...
The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. , drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-β1. To assess the effectiveness of preventing IUAs, experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid (NCHA) gel. According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium and reducing the abnormal deposition of fibrin, thus preventing IUA more effectively. This study provides a promising strategy for treating and preventing IUA.
PubMed: 38779348
DOI: 10.1093/rb/rbae043 -
Biological & Pharmaceutical Bulletin 2024Patch tests are often used in safety evaluations to identify the substance causing skin irritation, but the same substance can sometimes give positive or negative...
Patch tests are often used in safety evaluations to identify the substance causing skin irritation, but the same substance can sometimes give positive or negative results depending on the test conditions. Here, we investigated differences in the skin penetration of two test compounds under different application conditions. We studied the effects of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant polysorbate 80 (PS) on skin penetration of the preservatives methylisothiazolinone (MT) and methylchloroisothiazolinone (MCT), which are used in cosmetics such as shampoos. The skin permeation of MT was enhanced by SDS but was unchanged by PS. Skin impedance decreased in the presence of SDS whereas PS had the same effect as the control aqueous solution, suggesting that SDS reduction of the barrier function of skin affects the permeation of MT, a hydrophilic drug. Application of a mixture of MCT and MT in the presence of SDS did not affect the skin permeation of MCT whereas the permeation of MT was enhanced by SDS, indicating that the skin permeation of MCT is less affected by SDS than is MT. Thus, attention should be paid to the possible effect of co-solutes, especially hydrophilic drugs.
Topics: Thiazoles; Surface-Active Agents; Skin Absorption; Polysorbates; Sodium Dodecyl Sulfate; Skin; Animals; Preservatives, Pharmaceutical; Swine; Cosmetics; Electric Impedance; Permeability
PubMed: 38777759
DOI: 10.1248/bpb.b24-00127 -
Journal of Pharmaceutical Sciences May 2024The formulation of paediatric medicines faces significant challenges to meet the requirements for safe and accurate administration, while maintaining a suitable taste....
The formulation of paediatric medicines faces significant challenges to meet the requirements for safe and accurate administration, while maintaining a suitable taste. Multiparticulate formulations have a strong potential to address these challenges because they combine dose flexibility with ease of administration. Understanding the stability of multiparticulate formulations over storage as a function of time and environmental parameters, such as humidity and temperature, is important to manage their commercialisation and use. In this work, we have expanded the toolkit of available techniques for studying multiparticulates beyond those such as scanning electron microscopy (SEM) and confocal laser scanning microscopy. We include advanced methods of environmentally-controlled SEM to monitor temperature- and humidity-induced changes in-situ, and a variety of Raman spectroscopies including stimulated Raman scattering microscopy to identify and localise the different ingredients at the surface and inside the multiparticulates. These techniques allowed unprecedented monitoring of specific changes to the particulate structure and distribution of individual ingredients due to product aging. These methods should be considered as valuable novel tools for in-depth characterisation of multiparticulate formulations to further understand chemical changes occurring during their development, manufacturing and long-term storage. We envisage these techniques to be useful in furthering the development of future medicine formulations.
PubMed: 38777176
DOI: 10.1016/j.xphs.2024.05.004 -
Journal of Nanobiotechnology May 2024Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses, and...
Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses, and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum-gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum-gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1β, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA.
Topics: Curcumin; Chondroitin Sulfates; Gelatin; Animals; Nanocapsules; Nanoparticles; Mice; Tragacanth; RAW 264.7 Cells; Oxidative Stress; Arthritis, Rheumatoid; Male; Particle Size; Anti-Inflammatory Agents; Macrophages; Drug Liberation; Rats
PubMed: 38769551
DOI: 10.1186/s12951-024-02540-2