Synthesis, Optimization and Molecular Self-Assembly Behavior of Alginate-g-Oleylamine Derivatives Based on Ugi Reaction for Hydrophobic Drug Delivery.

To achieve the optimal alginate-based oral formulation for delivery of hydrophobic drugs, on the basis of previous research, we further optimized the synthesis process parameters of alginate-g-oleylamine derivatives (Ugi-FOlT) and explored the effects of different degrees of substitution (DSs) on the molecular self-assembly properties of Ugi-FOlT, as well as the in vitro cytotoxicity and drug release behavior of Ugi-FOlT. The resultant Ugi-FOlT exhibited good amphiphilic properties with the critical micelle concentration (CMC) ranging from 0.043 mg/mL to 0.091 mg/mL, which decreased with the increase in the DS of Ugi-FOlT. Furthermore, Ugi-FOlT was able to self-assemble into spherical micellar aggregates in aqueous solution, whose sizes and zeta potentials with various DSs measured by dynamic light scattering (DLS) were in the range of 653 ± 25~710 ± 40 nm and -58.2 ± 1.92~-48.9 ± 2.86 mV, respectively. In addition, RAW 264.7 macrophages were used for MTT assay to evaluate the in vitro cytotoxicity of Ugi-FOlT in the range of 100~500 µg/mL, and the results indicated good cytocompatibility for Ugi-FOlT. Ugi-FOlT micellar aggregates with favorable stability also showed a certain sustained and pH-responsive release behavior for the hydrophobic drug ibuprofen (IBU). Meanwhile, it is feasible to control the drug release rate by regulating the DS of Ugi-FOlT. The influence of different DSs on the properties of Ugi-FOlT is helpful to fully understand the relationship between the micromolecular structure of Ugi-FOlT and its macroscopic properties.

Chiral Selectivities of Permethylated α-, ß-, and γ-Cyclodextrins Containing Gas Chromatographic Stationary Phases towards Ibuprofen and Its Derivatives.

Ibuprofen is a well-known and broadly used, nonsteroidal anti-inflammatory and painkiller medicine. Ibuprofen is a chiral compound, and its two isomers have different biological effects, therefore, their chiral separation is necessary. Ibuprofen and its derivatives were used as model compounds to establish transportable structure chiral selectivity relationships. Chiral selectors were permethylated α-, ß-, and γ-cyclodextrins containing gas chromatographic stationary phases. The chiral selectivity of ibuprofen as a free acid and its various alkyl esters (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and isoamyl esters) derivatives were tested at different temperatures. Every tested stationary phase was capable of the chiral separations of ibuprofen in its free acid form. The less strong included S optical isomers eluted before R optical isomers in every separate case. The results offer to draw transportable guidelines for the chiral selectivity vs. analyte structures. It was recognized that the S isomers of free ibuprofen acid showed an overloading phenomenon, but the R isomer did not. The results were supported by molecular modeling studies.

Thermo-activated in situ rectal gel preparation for Ibuprofen using eutectic mixture.

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.

An Advanced Twin-Screw Granulation Technology: The use of Non-Volatile Solvents with High Solubilizing Capacity.

PURPOSE: Twin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders. METHODS: Herein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat® 603, Affinisol™, and AQOAT®). RESULTS: The physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity. CONCLUSIONS: Overall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings.

Development of 3D-printed dual-release fixed-dose combination through double-melt extrusion.

This study aimed to develop a 3D-printed fixed-dose combination tablet featuring differential release of two drugs using double-melt extrusion (DME). The hot-melt extrusion (HME) process was divided into two steps to manufacture a single filament containing the two drugs. In Step I, a sustained-release matrix of acetaminophen (AAP) was obtained through HME at 190 °C using Eudragit® S100, a pH-dependent polymer with a high glass transition temperature. In Step II, a filament containing both sustained-release AAP from Step I and solubilized ibuprofen (IBF) was fabricated via HME at 110 °C using a mixture of hydroxy propyl cellulose (HPC-LF) and Eudragit® EPO, whose glass transition temperatures make them suitable for use in a 3D printer. A filament manufactured using DME was used to produce a cylindrical 3D-printed fixed-dose combination tablet with a diameter and height of 9 mm. To evaluate the release characteristics of the manufactured filament and 3D-printed tablet, dissolution tests were conducted for 10 h under simulated gastrointestinal tract conditions using the pH jump method with the United States Pharmacopeia apparatus II paddle method at 37 ± 0.5 °C and 50 rpm. Dissolution tests confirmed that both the sustained-release and solubilized forms of AAP and IBF within the filament and 3D-printed tablet exhibited distinct drug-release behaviors. The physicochemical properties of the filament and 3D-printed tablet were confirmed by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy. HME transforms crystalline drugs into amorphous forms, demonstrating their physicochemical stability. Scanning electron microscopy and confocal laser scanning microscopy indicated the presence of sustained AAP granules within the filament, confirming that the drugs were independently separated within the filament and 3D-printed tablets. Finally, sustained-release AAP and solubilized IBF were independently incorporated into the filaments using DME technology. Therefore, a dual-release 3D-printed fixed-dose combination was prepared using the proposed filament.

Blend uniformity monitoring in a continuous manufacturing mixing process for a low-dosage formulation using a stream sampler and near infrared spectroscopy.

Continuous manufacturing has the potential to offer several benefits for the production of oral solid dosage forms, including reduced costs, low-scale equipment, and the application of process analytical technology (PAT) for real-time process control. This study focuses on the implementation of a stream sampler to develop a near infrared (NIR) calibration model for blend uniformity monitoring in a continuous manufacturing mixing process. Feeding and mixing characterizations were performed for three loss-in-weight feeders and a commercial continuous mixer to prepare powder blends of 2.5-7.5 % w/w ibuprofen DC 85 W with a total throughput of 33 kg/h. The NIR spectral acquisition was performed after the mixing stage using a stream sampler for flowing powders. A continuous mixer shaft speed of 250 RPM was selected to operate the mixing process based on a variability analysis developed with in-line spectral data acquired using the stream sampler at 6 RPM. A partial least squares regression (PLS-R) model was performed and evaluated, yielding a root-mean-square error of prediction (RMSEP) of 0.39 % w/w and a bias of 0.05 % w/w. An independent experimental run conducted two days later revealed that the continuous mixing process and the NIR calibration model presented low day-to-day variation. The minimum practical error (MPE) and sill values through variographic analysis showed low variance associated with the sampling process using the stream sampler. Results demonstrated the promising capacity of the stream sampler coupled to an NIR probe to be implemented within continuous manufacturing processes for the real-time determination of API concentration.

Optimization of TiO2-natural hydrogels for paracetamol and ibuprofen degradation in wastewaters.

Agarose/micrometer titanium dioxide (TiO2) beads were essayed to test the photocatalytic capacity of two of the most widely prescribed drugs worldwide: paracetamol and ibuprofen. Although the initial tests demonstrated promising degradation rates for both drugs, the presence of turbidity, due to TiO2 leakage, during the photocatalytic essays induced to improve the stability of the photocatalytic composites. Among the different strategies adopted to strengthen such materials, crosslinking with citric acid and the use of alternative gelling agents: gellan, agargel™, and agar were chosen. Composites obtained by merging both strategies were characterized and employed to degrade both drugs under a simulated light that mimics the solar spectrum (indoor). Considering the superior degradation rates obtained when agar and agarose were used to shape the titanium oxide particles (up to 70-75% of drug destruction), such composites were subjected to a more realistic experiment (outdoor): solar illumination, tap water, and higher volumes, that should facilitate its ulterior scale up as a real wastewater depollution procedure. Degradation rates between 80 and 90% are attained under such conditions for both drugs.

Anticancer potential of NSAID-derived tris(pyrazolyl)methane ligands in iron(II) sandwich complexes.

Tris(pyrazolyl)methane (tpm), 2,2,2-tris(pyrazolyl)ethanol (tpmOH) and its esterification derivatives with ibuprofen and flurbiprofen (tpmIBU and tpmFLU) were used as ligands to obtain complexes of the type [Fe(tpmX)2]Cl2 (1-4). The tpmIBU and tpmFLU ligands and corresponding complexes 3 and 4 were characterized by IR and multinuclear NMR spectroscopy, and the structure of tpmIBU was elucidated by single crystal X-ray diffraction. Complexes 1-4 were also assessed for their behaviour in aqueous media (solubility in D2O, octanol/water partition coefficient, stability in physiological-like conditions). The antiproliferative activity of ligands and complexes was determined on A2780, A2780cis and A549 cancer cell lines and the non-cancerous HEK 293T and BJ cell lines. The ligands and complexes were investigated for their ability to inhibit COX-2 (cyclooxygenase) and HNE (4-hydroxynonenal) enzymes. Complexes 3 and 4 exhibited cytotoxicity that may be attributed predominantly to their bioactive fragments, while DNA binding and enhancement of ROS production do not appear to play any significant role.

Effect of Ibuprofen as an Albumin Binder on Melanoma-Targeting Properties of 177Lu-Labeled Ibuprofen-Conjugated Alpha-Melanocyte-Stimulating Hormone Peptides.

The purpose of this study was to examine how the introduction of ibuprofen (IBU) affected tumor-targeting and biodistribution properties of 177Lu-labeled IBU-conjugated alpha-melanocyte-stimulating hormone peptides. The IBU was used as an albumin binder and conjugated to the DOTA-Lys moiety without or with a linker to yield DOTA-Lys(IBU)-GG-Nle-CycMSHhex {1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Lys(IBU)-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex peptides. Their melanocortin-receptor 1 (MC1R) binding affinities were determined on B16/F10 melanoma cells first. Then the biodistribution of 177Lu-labeled peptides was determined on B16/F10 melanoma-bearing C57 mice at 2 h postinjection to choose the lead peptide for further examination. The full biodistribution and melanoma imaging properties of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex were further evaluated using B16/F10 melanoma-bearing C57 mice. DOTA-Lys(IBU)-GG-Nle-CycMSHhex, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex displayed the IC50 values of 1.41 ± 0.37, 1.52 ± 0.08, 0.03 ± 0.01, and 0.58 ± 0.06 nM on B16/F10 melanoma cells, respectively. 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex exhibited the lowest liver and kidney uptake among all four designed 177Lu peptides. Therefore, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was further evaluated for its full biodistribution and melanoma imaging properties. The B16/F10 melanoma uptake of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was 19.5 ± 3.12, 24.12 ± 3.35, 23.85 ± 2.08, and 10.80 ± 2.89% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. Moreover, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex could clearly visualize the B16/F10 melanoma lesions at 2 h postinjection. The conjugation of IBU with or without a linker to GGNle-CycMSHhex affected the MC1R binding affinities of the designed peptides. The charge of the linker played a key role in the liver and kidney uptake of 177Lu-Asp-IBU, 177Lu-Asn-IBU, and 177Lu-Dab-IBU. 177Lu-Asp-IBU exhibited higher tumor/liver and tumor/kidney uptake ratios than those of 177Lu-Asn-IBU and 177Lu-Dab-IBU, underscoring its potential evaluation for melanoma therapy in the future.

Sustainable photoelectrocatalytic oxidation of antibiotics using Ag-CoFe2O4@TiO2 heteronanostructures for eco-friendly wastewater remediation.

Developing high-performance and durable catalysts presents a significant challenge for oxidizing toxic inorganic and pharmaceutical compounds in wastewater. Recently, there has been a surge in the development of new heterogeneous catalysts for degrading pharmaceutical compounds, driven by advancements in electrocatalysts and photoelectrocatalysts. In this study, a plasmonic Ag nanoparticles decorated CoFe2O4@TiO2 heteronanostructures have been successfully designed to fabricate a high-performing photoelectrode for the oxidation of pharmaceutical compounds. The developed Ag-CoFe2O4@TiO2 possessed a higher electrochemical stability and effectively harvested the UV to visible and NIR radiation in sunlight which generates the enormous photochemical reactive species that involved in the oxidation of ibuprofen in wastewater. Under direct sunlight irradiation, Ag-CoFe2O4@TiO2 achieved complete oxidation of ibuprofen in wastewater at 0.8 V vs RHE. This indicates that metallic Ag nanoparticles are involved in the charge separation and transport of charge carriers from the photoactive sites of CoFe2O4@TiO2, promoting the generation of abundant hydroxy, oxy, and superoxide radicals that actively break the bonds of ibuprofen. Additionally, oxidation agents such as urea and H2O2 were utilized to enhance the formation of superoxide ions and hydroxyl radicals, which rapidly participate in the oxidation of ibuprofen. Significantly, testing for recyclability confirmed the stability of the Ag-CoFe2O4@TiO2 photoanode, ensuring its suitability for prolonged use in photoelectrochemical advanced oxidation processes. Integrating Ag-CoFe2O4@TiO2 photoanodes into water purification systems could enhance economic feasibility, reduce energy consumption, and improve efficiency.

Uni-directional release of ibuprofen from an asymmetric fibrous membrane enables effective peritendinous anti-adhesion.

Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.

Facilitating direct compaction tableting of fine cohesive APIs using dry coated fine excipients: Effect of the excipient size and amount of coated silica.

The possibility of attaining direct compression (DC) tableting using silica coated fine particle sized excipients was examined for high drug loaded (DL) binary blends of APIs. Three APIs, very-cohesive micronized acetaminophen (mAPAP, 7 µm), cohesive acetaminophen (cAPAP, 23 µm), and easy-flowing ibuprofen (IBU, 53 µm), were selected. High DL (60 wt%) binary blends were prepared with different fine-milled MCC-based excipients (ranging 20- 37 µm) with or without A200 silica coating during milling. The blend flowability (flow function coefficient -FFC) and bulk density (BD) of the blends for all three APIs were significantly improved by 1 wt% A200 dry coated MCCs; reaching FFC of 4.28 from 2.14, 7.82 from 2.96, and > 10 from 5.57, for mAPAP, cAPAP, and IBU blends, respectively, compared to the uncoated MCC blends. No negative impact was observed on the tablet tensile strength (TS) by using dry coated MCCs despite lower surface energy of silica. Instead, the desired tablet TS levels were reached or exceeded, even above that for the blends with uncoated milled MCCs. The novelty here is that milled and silica coated fine MCCs could promote DC tableting for cAPAP and IBU blends at 60 wt% DL through adequate flowability and tensile strength, without having to dry coat the APIs. The effect of the silica amount was investigated, indicating lesser had a positive impact on TS, whereas the higher amount had a positive impact on flowability. Thus, the finer excipient size and silica amounts may be adjusted to potentially attain blend DC processability for high DL blends of fine APIs.

Synthesis, molecular dynamics simulation, and evaluation of biological activity of novel flurbiprofen and ibuprofen-like compounds.

The frequent use of anti-inflammatory drugs and the side effects of existing drugs keep the need for new compounds constant. For this purpose, flurbiprofen and ibuprofen-like compounds, which are frequently used anti-inflammatory compounds in this study, were synthesized and their structures were elucidated. Like ibuprofen and flurbiprofen, the compounds contain a residue of phenylacetic acid. On the other hand, it contains a secondary amine residue. Thus, it is planned to reduce the acidity, which is the biggest side effect of NSAI drugs, even a little bit. The estimated ADME parameters of the compounds were evaluated. Apart from internal use, local use of anti-inflammatory compounds is also very important. For this reason, the skin permeability values of the compounds were also calculated. And it has been found to be compatible with reference drugs. The COX enzyme inhibitory effects of the obtained compounds were tested by in vitro experiments. Compound 2a showed significant activity against COX-1 enzyme with an IC50 = 0.123 + 0.005 µM. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies.

Efficiently photocatalysis activation of peroxymonosulfate by bimetallic metal-organic frameworks Mn-MIL-53(Fe) for ibuprofen degradation: Synergistic efficiency, mechanism and degradation pathways.

In this study, a UV-driven photocatalytic activation of peroxymonosulfate (PMS) system was constructed using bimetallic metal-organic frameworks to degrade pharmaceuticals and personal care products (PPCPs). Mn-MIL-53(Fe) was successfully synthesised by adjusting the doping ratio of Mn using solvothermal method. The removal of ibuprofen (IBP) by UV/Mn-MIL-53(Fe)/PMS process was as high as 79.7% in 30 min with a Mn doping ratio of 1.0 (molar ratio of Mn to Fe), and the reaction rate constant was 26.9% higher than undoped. Mn-MIL-53(Fe) had been systematically characterized in terms of its physical structure, microscopic morphology, surface functional groups and photoelectric properties. The mechanism investigation revealed that the cycling of Mn and Fe accelerated the rate of electron transfer in the system, which significantly increased the activation efficacy of PMS to generate more hydroxyl and sulfate radicals for IBP degradation. A total of 13 transformation products were detected during the degradation of IBP by the UV/Mn-MIL-53(Fe)/PMS process. Theoretical calculations were used to predict the sites on the IBP molecule that were vulnerable to attack, and four possible degradation pathways were deduced. The excellent stability and efficient catalytic properties of Mn-MIL-53(Fe) provided a promising solution to the problem of water treatment contaminated with PPCPs.

Toxicological study on ibuprofen and selenium in freshwater mussel Lamellidens marginalis and exploring the microbial cytochrome through modelling and quantum mechanics approaches for its toxicity degradation in contaminated environment.

Toxicological stress in aquatic organisms is caused by the discharge of hundreds of toxic pollutants and contaminants among which the current study concentrates on the toxic effect of non-steroidal anti-inflammatory drug ibuprofen (IBF) and the trace element selenium (Se). In this study, IBF and Se toxicity on freshwater mussel Lamellidens marginalis was studied for 14 days, and in silico predictions for their degradation were made using Molecular modelling and Quantum Mechanical approaches. The degrading propensity of cytochrome c oxidase proteins from Trametes verticillatus and Thauera selenatis (Turkey tail fungi and Gram-negative bacteria) is examined into atom level. The results of molecular modelling study indicate that ionic interactions occur in the T. selenatis-HEME bound complex by Se interacting directly with HEME, and in the T. versicolor-HEME bound complex by IBF bound to a nearby region of HEME. Experimental and theoretical findings suggest that, the toxicological effects of Se and IBF pollution can be reduced by bioremediation with special emphasis on T. versicolor, and T. selenatis, which can effectively interact with Se and IBF present in the environment and degrade them. Besides, this is the first time in freshwater mussel L. marginalis that ibuprofen and selenium toxicity have been studied utilizing both experimental and computational methodologies for their bioremediation study.

Multifunctional tunable Cu2O and CuInS2 quantum dots on TiO2 nanotubes for efficient chemical oxidation of cholesterol and ibuprofen.

In this study, a CuInS2/Cu2O/TiO2 nanotube (TNT) heterojunction-based hybrid material is reported for the selective detection of cholesterol and ibuprofen. Anodic TNTs were co-decorated with Cu2O and CuInS2 quantum dots (QDs) using a modified chemical bath deposition (CBD) method. QDs help trigger the chemical oxidation of cholesterol by cathodically generating hydroxyl radicals (˙OH). The small size of QDs can be used to tune the energy levels of electrode materials to the effective redox potential of redox species, resulting in highly improved sensing characteristics. Under optimal conditions, CuInS2/Cu2O/TNTs show the highest sensitivity (∼12 530 µA mM-1 cm-2, i.e. up to 11-fold increase compared to pristine TNTs) for cholesterol detection with a low detection limit (0.013 µM) and a fast response time (1.3 s). The proposed biosensor was successfully employed for the detection of cholesterol in real blood samples. In addition, fast (4 s) and reliable detection of ibuprofen (with a sensitivity of ∼1293 µA mM-1 cm-2) as a water contaminant was achieved using CuInS2/Cu2O/TNTs. The long-term stability and favourable reproducibility of CuInS2/Cu2O/TNTs illustrate a unique concept for the rational design of a stable and high-performance multi-purpose electrochemical sensor.

A novel insight of degradation ibuprofen in aqueous by catalytic ozonation with supported catalyst: Supports effect on ozone mass transfer.

Catalytic ozonation is an effective wastewater purification process. However, the low ozone mass transfer in packed bubble columns leads to low ozone utilization efficiency (OUE), poor organic degradation performance, and high energy consumption. Therefore, there is an urgent need to develop efficient supported catalysts that can enhance mass transfer and performance. However, the reaction mechanism of the support on ozone mass transfer remains unclear, which hinders the development of catalytic ozonation applications. In this study, lava rocks (LR)-supported catalysts, specifically CuMn2O4@LR and MnO2Co3O4@LR, were proposed for catalytic ozonation of IBP degradation due to their superior catalytic activity, stability, and high OUE. Addition of CuMn2O4@LR or MnO2Co3O4@LR increased IBP removal efficiency from 85% to 91% or 88%, and reduced energy consumption from 2.86 to 2.14 kWh/m3 or 2.60 kWh/m3, respectively. This improvement was attributed to LR-supported catalysts enhancing mass transfer and promoting O3 decomposition to generate •OH and •O2-, leading to IBP degradation. Furthermore, this study investigated the effects of ozone dose, supporter sizes, and catalyst components on ozone-liquid mass transfer. The results revealed that the size of the supporter influenced stacked porosity and consequently affected ozone mass transfer. Larger-sized LR (kLa= 0.172 min-1) exhibited better mass transfer compared to smaller-sized supports. Based on these findings, it was concluded that both CuMn2O4@LR and MnO2Co3O4@LR are potential catalysts for catalytic ozonation in residual IBP degradation of pharmaceutical wastewater, and LR showed good credibility as a catalyst supporter. Understanding the effects of supporters and active components on ozone mass transfer provides a fundamental principle for designing supported catalysts in catalytic ozonation applications.

Medicinal Anti-Inflammatory Patch Loaded with Lavender Essential Oil.

Transdermal drug delivery offers a promising alternative for administering medications like ibuprofen, known for its analgesic and anti-inflammatory properties, with reduced gastrointestinal side effects compared to oral administration. This study explored the potential synergistic effects of combining ibuprofen with lavender essential oil (LEO) in transdermal patches. The composition of LEO was analyzed, revealing predominant compounds such as linalyl acetate and linalool, which are known for their analgesic and anti-inflammatory properties. The physicochemical properties of the patches were investigated, indicating improved cohesion with the addition of LEO. Additionally, thermal stability assessments demonstrated enhanced stability with LEO incorporation with an increase in onset decomposition temperature from 49.0 to 67.9 °C. The antioxidant activity of patches containing LEO was significantly higher with a free radical scavenging ability of 79.13% RSA compared to 60% RSA in patches without LEO. Release and permeation studies showed that patches with LEO exhibited an increased permeation of ibuprofen through the skin with 74.40% of the drug released from LEO-containing patches compared to 36.29% from patches without LEO after 24 h. Moreover, the permeation rate was notably faster with LEO, indicating quicker therapeutic effects. The inclusion of LEO in transdermal patches containing ibuprofen holds promise for enhancing drug delivery efficiency and therapeutic effectiveness, offering a potential strategy for improved pain management with reduced side effects.

Rubber oily liquids as transdermal and periodontal pocket drug delivery systems.

This study investigates the incorporation of block natural rubber (NR) as a viscosity-inducing agent in NR oily liquids designed for drug delivery systems. A variety of liquids, encompassing natural oils, synthetic and non-oil liquids, and a eutectic mixture, were incorporated with NR using solvent displacement technique. Successful formulations were achieved for several oily liquids, with viscosity correlating to NR concentration. Particularly, a eutectic mixture of menthol and camphor exhibited optimal viscosity by direct dissolving enabling the development of transdermal ibuprofen delivery and injectable azithromycin for periodontitis treatment. NR prolonged the release of both drugs. The extended-release ibuprofen system holds promise for transdermal applications, while the azithromycin system displayed inhibitory effects against Staphylococcus aureus, Streptococcus mutans, and Porphyromonas gingivalis, suggesting potential for periodontitis treatment. Overall, this investigation advances the development of NR oily liquids as a versatile drug delivery system that can be applied both on the skin and for the local injection into the periodontal pocket, showcasing promise for various therapeutic applications.

Thermal effects and drugs competition on the palmitate binding capacity of human serum albumin.

Human serum albumin (HSA) is the most abundant plasma protein of the circulatory system. It is a multidomain, multifunctional protein that, combining diverse affinities and wide specificity, binds, stores, and transports a variety of biological compounds, pharmacores, and fatty acids. HSA is finding increasing uses in drug-delivery due to its ability to carry functionalized ligands and prodrugs. All this raises the question of competition for binding sites occupancy in case of multiple ligands, which in turn influences the protein structure/dynamic/function relationship and also has an impact on the biomedical applications. In this work, the effects of interactive binding of palmitic acid (PA), warfarin (War) and ibuprofen (Ibu) on the thermal stability of HSA were studied using DSC, ATR-FTIR, and EPR. PA is a high-affinity physiological ligand, while the two drugs are widely used for their anticoagulant (War) and anti-inflammatory (Ibu) efficacy, and are exogenous compounds that accommodate in the deputed drug site DS1 and DS2, respectively overlapping with some of the fatty acid binding sites. The results indicate that HSA acquires the highest thermal stability when it is fully saturated with PA. The binding of this physiological ligand does not hamper the binding of War or Ibu to the native state of the protein. In addition, the three ligands bind simultaneously, suggesting a synergic cooperative influence due to allosteric effects. The increased thermal stability subsequent to binary and multiple ligands binding moderates protein aggregation propensity and restricts protein dynamics. The biophysics findings provide interesting features about protein stability, aggregation, and dynamics in interaction with multiple ligands and are relevant in drug-delivery.