Steady-state Flux Research Articles

Formulation, Quality Control and Stability Study of Pediatric Oral Dextrose Gel

Background/Objective: Little information is available on the stability and quality controls of compounded 40% dextrose gel required to ensure its safe use in the treatment and prevention of neonatal hypoglycemia. Whether its efficacy relies on buccal absorption also remains uncertain. This study investigates the stability, microbiological safety, rheological properties and dextrose diffusion of a compounded 40% oral dextrose gel, ensuring it can be widely compounded and stored for clinical use. Methods: A 40% dextrose gel compounded with anhydrous dextrose, carboxymethylcellulose, citric acid, sorbic acid and sterile water was subjected to quality control measures including a dextrose content assay, degradation product analysis, microbiological testing and preservative efficacy. Stability studies were conducted at refrigerated (4–8 °C) and ambient temperatures for 7 days and 3 months, respectively. Rheological properties were assessed, and dextrose permeation was measured through an artificial membrane model that mimics a biological membrane. Results: The compounded gel demonstrated stability for up to 7 days at ambient temperature and 90 days when refrigerated. The dextrose content remained within the acceptable range (90–110%) and microbiological tests confirmed compliance with safety standards. The gel exhibited the consistent rheological properties and shear-thinning behavior appropriate for oral mucosal administration. In vitro permeation studies showed no evidence of dextrose diffusion with a long lag time followed by a low steady-state permeation flux. Conclusions: This study validates the compounding process of a stable 40% oral dextrose gel formulation for neonatal hypoglycemia management, which meets quality control criteria and can be safely administered in clinical practice, offering a cost-effective and safe alternative for neonatal care.

Evaluating Dermal Absorption of Perfluorooctanoic Acid (PFOA) and Implications for Other Per- and Polyfluoroalkyl Substances (PFAS).

To date, only four studies directly measured dermal absorption kinetics of perfluorooctanoic acid (PFOA) in human skin. Reported kinetic parameters spanned two to five orders of magnitude, demonstrating the need to determine the causes of variability and identify the most appropriate dermal absorption factors for use in exposure assessments. We evaluated the reliability and physiological relevance of studies that measured PFOA fractional absorption, steady-state flux (Jss), and dermal permeability coefficient (Kp). We verified whether the reported kinetic parameters were measured under appropriate conditions (i.e., fractional absorption under finite dose conditions, and Jss and Kp under infinite dose conditions). We recommend the following values measured at the approximate pH of the skin, and in aqueous solvents or relevant consumer product matrices, for use as provisional values in PFOA exposure assessments: 1.6% fractional absorption under finite dose conditions, and 0.132 μg/cm2-hr and 0.000044 cm/hr for Jss and Kp, respectively, under infinite dose conditions. Using the recommended absorption factors, we estimated PFOA exposures in children from soil and water via dermal and ingestion routes. Our results indicate low dermal absorption of PFOA relative to ingestion, and low dermal absorption is expected for per- and polyfluoroalkyl substances (PFAS) with physicochemical properties similar to PFOA.

Enhancement of Transdermal Drug Delivery: Integrating Microneedles with Biodegradable Microparticles.

This investigation aimed to enhance transdermal methotrexate delivery through human skin by employing Dr. Pen microneedles and poly(d,l-lactide-co-glycolide) acid microparticles formulated from eight polymer grades (Expansorb DLG 95-4A, DLG 75-5A, DLG 50-2A, DLG 50-5A, DLG 50-8A, DLG 50-6P, DLG 50-7P, and DLL 10-15A). A comprehensive characterization of the microparticles was performed, encompassing various parameters such as size, charge, morphology, microencapsulation efficiency, yield, release kinetics, and chemical composition. The efficacy of microneedles in disrupting skin integrity was demonstrated by scanning electron microscopy, dye binding, histological examination, confocal laser microscopy, and pore size analysis. Microneedle-mediated skin microporation led to a substantial reduction in skin electrical resistance and a concomitant increase in transepidermal water loss. In vitro permeation experiments using human skin delivered microparticles into microporated skin and demonstrated a considerable difference in methotrexate delivery among the polymer groups. Microneedle treatment significantly amplified cumulative drug delivery, steady-state flux, diffusion coefficient, permeability coefficient, and drug concentration within skin layers while concurrently diminishing lag time (p < 0.05). Furthermore, a robust correlation was established between microparticle properties (cumulative release, release rate, encapsulation efficiency) and drug deposition in the skin. In conclusion, the synergistic combination of Dr. Pen microneedles and PLGA microparticles facilitated enhanced and regulated transdermal methotrexate delivery.

FORMULATION OF TOLNOFTATE LOADED CUBOSOMES FOR EFFECTIVE TRANSDERMAL DELIVERY: AN IN VITRO AND EX-VIVO STUDY

Objective: The novel topical application has several benefits over traditional dosing forms, such as preventing gastrointestinal discomfort, lowering liver drug metabolism, and increasing medication bioavailability. Tolnaftate is used as potential anti-fungal agent various fungal infections. Methods: The cubosomes were formulated by emulsification technique using probe sonicator. The formulation was optimized using different concentrations of glyceryl monooleate and poloxamer 407. Results: The formed cubosomes dispersion was subjected to entrapment efficiency, surface morphology, particle size, in vitro release, anti-fungal study and ex-vivo study. The improved formulation was then transformed to a cubosomal hydrogel by the addition of carbopol 934. The average particle size of the optimised cubosomes was 208.0 nm. Zeta potential has been found to be 49.8 mV, with an entrapment efficiency of almost 90.0%. The drug steady-state flux (Jss) values for Tolnaftate Cubosomal formulation, marketed formulation, and plain drug gel were nearly 11.98, 10.23, and 10.06 g/cm2. h. As compared to standard marketed preparation, the cubosome-loaded formulation demonstrated enhanced penetration, extended deposition, and prolonged drug release. Conclusion: The drug had low solubility and permeability; it was overcome and produced superior outcomes in the form of cubosomes, which considerably increased the drug's solubility and permeability.

Quality by Design and Characterization of Nimodipine Novel Carriers for the Treatment of Hypertension: Assessment of the Pharmacokinetic Profile

Background: Nimodipine is a highly lipophilic anti-hypertensive drug having 13% oral bioavailability (log P 3.41). Nimodipine is a prominent calcium channel blocker that must be given intravenously for an extended period of time (1-2 weeks) in order to treat cerebral vasospasm. It might be possible to substitute a sustained-release biodegradable formulation for the ongoing intravenous infusion used in this traditional therapy. Objectives: The primary goal of this study was to formulate and evaluate the potentiality of ethosomes to deliver nimodipine, a potent water-insoluble anti-hypertensive drug, through the deeper layers of the skin. The greatest challenge for drug formulation is its poor oral bioavailability and solubility. Methods: Nimodipine-loaded ethosomal gel was developed for transdermal drug delivery to increase solubility and skin penetration and to promote oral bioavailability. Central composite design employing a thin-film hydration method was used to prepare and optimize ethosomes. A better dispersion medium for nimodipine's preparation in ethosomes was selected based on the effect. The design consisted of independent variables as lipid (X1), ethanol (X2), and sonication time (X3). Concentrations were manipulated to examine the effects on three responses, namely the %entrapment efficiency (Y1), vesicle size (Y2), and %cumulative drug release (Y3). Surface morphology and other in vitro tests were used to identify ethosomes containing nimodipine. The preparation of ethosomal gel formulations began with incorporating a single ethosomal formulation (F4) into various concentrations of gelling agents. These studies performed physicochemical characterization, compatibility testing, and in vitro drug release tests on ethosomal gels. In vivo studies involving hypertensive rats were conducted after skin permeation, and ex vivo studies were performed. In order to assess the drug's permeability and deposition, we employed the abdomen skin of rats. Results: The optimal process parameters resulted in ethosomes with 89.9 ± 0.19 percent entrapment efficiency, a vesicle size of 102.37 ± 5.84 nm, and a cumulative drug release of 98.3 ± 0.13%. pH and drug content measurements were consistent with the homogeneous ethosomal gels. Viscosity was found to increase with the spreadability. The ethosomal gel formulation (G2) met the regulatory standards regarding appearance, spreadability, viscosity, and in vitro release studies. Compared to pure nimodipine, ethosomal suspension (F4) and ethosomal gel (G2) formulations had higher ex vivo permeation, steady-state flux, and drug retention. Rats' mean arterial pressure (146.11 ± 0.84 mmHg) was significantly lower (p &lt; 0.01) after after two hours of the experiment than it had been (p &lt; 0.001) (98.88 ± 0.63 mmHg) after six hours. Conclusion: To summarize, ethosomal gels have been found to be lipid carriers that enhance skin permeation and extend the anti-hypertensive effect of nimodipine. Compared to plain gel, ex vivo drug permeation through rat abdominal skin in ethosomal gel was enhanced. Gel-based ethosomal transdermal drug delivery formulations of nimodipine can be used to achieve a faster rate and extend the duration of drug delivery by more than 24 hours.

The Role of Thickening Agent Proportions in Optimizing Nanoemulsion Gel for Dermatophytosis Treatment.

Adjusting thickening agent proportions in nanoemulsion gel (NG) balances its transdermal and topical delivery properties, making it more effective for dermatophytosis treatment. Carbomer 940 and α-pinene were used as model thickening agent and antifungal, respectively. A series of α-pinene NGs (αNG1, αNG2, αNG3) containing 0.5%, 0.75% and 1% (w/w) Carbomer 940 were developed and evaluated for stability, rheological properties, and skin irritation; assessed for ex vivo skin permeation, deposition, and fluorescent imaging of drug distribution within skin layers; and tested in vivo for efficacy against Trichophyton rubrum infection in guinea pigs, with PAS (Periodic Acid-Schiff) staining confirming fungal clearance. The steady-state skin flux rates of α-pinene over 24hours were αNG1 (46.93±2.52μg/cm²/h) > αNG2 (26.01±2.65μg/cm²/h) > αNG3 (11.36±1.69μg/cm²/h). The α-pinene deposition in the epidermis/dermis for αNG1 decreased substantially from 2h (62.74 ± 3.36μg/cm²) to 12h (11.7 ± 2.24μg/cm²). In contrast, αNG2 showed relatively sustained deposition with 2h (25.54 ± 2.67μg/cm²), 6h (57.32 ± 4.62μg/cm²) and 12h (23.69 ± 3.29μg/cm²). αNG3 exhibited a slow increase from 2h (18.32 ± 2.11μg/cm²) to 12h (36.78 ± 3.22μg/cm²). The αNG2 exhibited the highest efficacy and fungal clearance rates (71.42%, 79.17%), followed by αNG1 (55.34% and 60.42%), and αNG3(43.21%, 52.08%). Fluorescent imaging confirmed αNG2's higher drug deposition within the epidermis/dermis, while PAS staining showed a potent fungal clearance with αNG2. This study demonstrates that Carbomer 940 proportions significantly impact the transdermal performance of αNG. αNG2, with a moderate proportion, optimally enhances skin drug delivery and deposition, achieving superior therapeutic outcomes. These findings highlight the importance of optimizing thickening agent proportions to improve the efficacy of topical nanoemulsion gels.

Capsaicin nanocrystals burdened topical polymeric gel: An encouraging tactic for alleviation of paclitaxel-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is triggered by clinically recommended chemotherapeutics. Topical capsaicin (CAP) is a US-FDA-approved therapeutic entity for the mitigation of CIPN. Besides good skin permeation efficiency, CAP concentration in a topical dermal dosage form must be controlled due to its dose-dependent therapeutic and adverse effects. Therefore, in the present investigation, capsaicin nanocrystals (CAP-NCs) were scaled up using the nanoprecipitation technique. CAP-NCs exhibited 145.4±0.90nm particle size, 0.254±0.005 polydispersity index (PDI), -17.2±0.80mV surface charge (ζ), and markedly higher cumulative percentage drug release (85.68±0.89%) compared to pure CAP (12.56±0.57%) in 12h. Later, capsaicin nanocrystals burdened polymeric gel (CAP-NCs-Gel) was characterized using analytical and spectral techniques. Furthermore, CAP-NCs-Gel depicted remarkable textural properties, and desirable viscosity along with∼2.23-fold enhancement in permeability, ∼1.61-fold augmentation of CAP steady-state flux, and permeability coefficient. Additionally, the in vivo therapeutic efficacy assessment of CAP-NCs-Gel in the paclitaxel-induced peripheral neuropathy (PIPN) demonstrated remarkable improvements in mechanical hyperalgesia, heat hyperalgesia, cold allodynia, and locomotor behavior. Capsaicin nanocrystals burdened polymeric gel once-a-day (CAP-NCs-Gel-OD) and twice-a-day (CAP-NCs-Gel-TD) applications outstandingly diminished the levels of TNF-α (P<0.0001) and IL-6 (P<0.01) in the sciatic nerve homogenate in contrast to the positive control group and insignificant difference (P>0.05) was noticed compared to the normal control group. Correspondingly, significant modulation of oxidative stress biomarkers, and noticeable regeneration of nerve fibers, a typical arrangement of the axon, with preserved intact myelin sheath integrity were professed in sciatic nerve; aimed at diminishing neuroinflammation, oxidative stress, and mitigating nerve damage in PIPN. In conclusion, CAP-NCs-Gel is a top-notch nanotherapeutic for translating into a clinically viable dosage form for treating CIPN.

Development, in vitro and in vivo evaluation of film forming solutions for transdermal drug delivery of Zaltoprofen.

Zaltoprofen (ZAL) is a non-steroidal anti-inflammatory drug (NSAID) with a short half-life (∼2.8 h) due to extensive first pass metabolism. In this context, 16 different polymeric film forming solutions (PFFS) of ZAL were developed using different grades of Eudragits, Polyvinylpyrrolidones, Kollicoat MAE 100 P and Hydroxypropyl cellulose as film formers, and polyethylene glycol 400 as a plasticizer in equal parts of ethanol and isopropyl alcohol used as solvents. Of these solutions, F13 composed of Kollicoat MAE 100 P emerged as an optimal PFFS as it quickly formed a saturated film (10.25 ± 0.75 min) that displayed low drying time (3.00 ± 0.46 min), and high in vitro adhesion (2.67 ± 0.58). Ex vivo permeation studies conducted in Franz diffusion cell across porcine skin indicated that F13 displayed significantly higher (p < 0.001) steady state flux (8.64 ± 1.72 µg.cm-2.h-1), shorter lag time (∼3 h) and better skin content (2.55 ± 0.62 µg/mg) compared to other PFFS. Fourier Transform Infrared Spectroscopy (FT-IR) proved the chemical integrity of ZAL in polymeric film formed from F13, while Differential scanning calorimetry (DSC) and X-ray Diffractometry (XRD) proved the "anti-recrystallization potential" of PFFS. Anti-inflammatory studies in rats indicated that F13 significantly inhibited (ANOVA, p < 0.001) carrageenan induced paw edema for nearly 12 h compared to topical diclofenac used as standard. In addition, significantly elevated (ANOVA, p < 0.001) analgesic effect was noted in the hot plate test in rats treated with F13 compared to the standard for 12 h proving the superior efficacy of F13. Thus, PFFS by virtue of "in situ evaporative metamorphosis" induced supersaturation can be an attractive platform to deliver ZAL transdermally.

Energy-based bond graph models of glucose transport with SLC transporters.

The SLC (solute carrier) superfamily mediates the passive transport of small molecules across apical and basolateral cell membranes in nearly all tissues. In this paper we employ bond graph approaches to develop models of SLC transporters that conserve mass, charge and energy, respectively, and which can be parameterised for a specific cell and tissue type for which the experimental kinetic data is available. We show how analytic expressions that preserve thermodynamic consistency can be derived for a representative four- or six-state model, given reasonable assumptions associated with steady-state flux conditions. We present details on fitting parameters for SLC2A2 (a GLUT transporter) and SLC5A1 (an SGLT transporter) to experimental data and show how well the steady-state flux expressions match the full kinetic analysis. Since the bond graph approach will not be familiar to many readers, we provide a detailed description of the approach and illustrate its application to a number of familiar biophysical processes.

Calculation of in-situ steady-state heat flux on EAST lower divertor

Heat flux is a key issue in tokamak devices. The non-uniform high heat flux on Plasma-Facing Components (PFCs) has led to local severe damage, including cracks and melting, in current tokamaks such as EAST and WEST. To characterize the non-uniform heat flux loading on the divertor surfaces, the parallel incident heat flux q‖, the decay length λq along the radial direction and the Gaussian spreading width S are used. The q‖ can lead to a very high peak heat flux loading on the divertor surfaces, which may cause critical heat flux problems. Additionally, the decay length is a key consideration for future tokamak designs like ITER. Every effort on the present tokamak devices contributes to updating the scaling of the heat flux. In EAST, a calculation method based on a high spatial resolution IR camera is employed to obtain the heat flux and decay length. The main process involves comparing the surface temperature distribution calculated by Fluent simulation with that measured by an infrared camera. Taking a high heating source discharge (#123059 ∼ 10 MW heating source) as an example, the heat flux is as follows: q‖=216-14+19 MW/m2, with λq=6.2-1.1+1 mm, and S=1.2±0.4 mm; it is in line with Langmuir probe data. The infrared-based heat flux calculation method can calculate the peak incident heat flux and the decay length simultaneously, its result can help to update the scaling model of heat flux, thus not only helping to improve the present device but also offering important reference for future tokamaks

TRANSETHOSOMES FOR ENHANCED TRANSDERMAL DELIVERY OF METHOTREXATE AGAINST RHEUMATOID ARTHRITIS: FORMULATION, OPTIMISATION AND CHARACTERISATION

Objective: The study aimed to develop and optimise Methotrexate (MTX)-loaded Transethosomal Film-Forming Gel (TE FFG) for transdermal delivery to treat rheumatoid arthritis while alleviating the side associated with oral administration. Methods: The Transethosomes (TE) were prepared using the thin film hydration technique and incorporated into an FFG using chitosan. The Box-Behnken Design method was used to analyse the influence of independent variables such as the concentration of soya lecithin, surfactant, and ethanol on parameters including vesicle size, PDI (Polydispersity Index), zeta potential, and entrapment efficiency. The optimised transethosomal suspension was incorporated into the FFG using 3% chitosan and other excipients. In vitro drug release and ex vivo skin permeation of FFG were performed using Franz diffusion cells. Results: The vesicle size, PDI, zeta potential and entrapment efficiency of the optimised formulation of TE were 110.3 nm, 0.352,-14.4 mV and 49.36%, respectively. The Transmission Electron Microscopy (TEM) image showed that the vesicles were uniform and spherical. The in vitro drug release study was higher for Conventional (CL) FFG) than TE FFG and the drug release mechanism was fitted into the Higuchi model. The permeation was higher for TE FFG, with the steady-state flux being 1.55 times greater than the CL FFG. The skin irritation test on Wistar rats revealed no indication of irritation on the skin. The histopathology examination showed a significant reduction in the inflammatory cells in the treated group. Conclusion: Therefore, the results concluded that the formulated MTX-loaded TE FFG could be a potentially promising substitute for the oral delivery of methotrexate

Artemisinin emulgel ameliorates cartilage degradation in knee osteoarthritis: in vitro and in vivo studies.

Aim: Laboratory scale-up of artemisinin-loaded emulgel (ART-emulgel) was carried out and characterized for therapeutic performance in osteoarthritis (OA).Materials & methods: The solubility of ART in various oils, surfactants and co-surfactants were screened for construction of pseudo ternary phase diagram (TPD), followed by scale-up of artemisinin loaded nanoemulsion (ART-NE). ART-NE was amalgamated with Carbopol Ultrez 10-NF to prepare ART-emulgel that was later characterized invitro and invivo to analyze therapeutic efficacy in monosodium-iodoacetate (MIA) induced knee OA.Results: The droplet diameter of ART-NE was estimated to be 104.3±2.593nm with a polydispersity index of 0.245±0.019 in addition to ζ-potential of 0.434±0.028mV. Steady-state flux and permeability coefficient for ART-emulgel were estimated to be 0.651±0.031 µg.cm2/h and 0.245±0.011cm/h, respectively. ART-emulgel demonstrated 43.18% reduction in COX-2 level; 52.28% drop in IL-1β, and 88.78% alleviation of Tumor Necrosis Factor-α (TNF-α) level when compared with monosodium-iodoacetate induced OA rats. ART-emulgel and injectable ART (intra-articular; I.A) portrayed minor synovial erosion compared with blank and diclofenac emulgel. Histopathological evidences indicated restoration of cartilage integrity followed by reduction of OARSI scores in ART-emulgel when compared with disease control animals.Conclusion: ART-emulgel is a potential dosage form for translating into a clinically viable product for the management of OA.

Quality by design optimization of formulation variables and process parameters for enhanced transdermal delivery of nanosuspension.

This investigation aims to fabricate, characterize, and optimize organogel containing andrographolide nanosuspension to enhance transdermal drug delivery into and across the skinin vitro. We identified the critical material attributes (CMAs) and critical process parameters (CPPs) that impact key characteristics of andrographolide nanosuspension using a systematic quality-by-design approach. We prepared andrographolide nanosuspension using the wet milling technique and evaluated various properties of the formulations. The CMAs were types and concentrations of polymers, types and concentrations of surfactants, drug concentration, and lipid concentration. The CPPs were volume of milling media and milling duration. Mean particle size, polydispersity index, encapsulation efficiency, and drug loading capacity as critical quality attributes were selected in the design for the evaluation and optimization of the formulations. Furthermore, we developed and evaluated organogel formulation to carry andrographolide nanosuspension 0.05% w/w. Drug release and permeation studies were conducted to assess the drug release kinetics and transdermal delivery of andrographolide. We presented the alteration in the average particle size, polydispersity index, encapsulation efficiency, drug-loading capacity, and drug release among various formulations to select the optimal parameters. The permeation study indicated that organogel delivered markedly more drug into the receptor fluid and skin tissue than DMSO gel (n = 3, p < 0.05). This enhancement in transdermal drug delivery was demonstrated by cumulative drug permeation after 24h, steady-state flux, permeability coefficient, and predicted steady-state plasma concentration. Drug quantity in skin layers, total delivery, delivery efficiency, and topical selectivity were also reported. Conclusively, andrographolide nanosuspension-loaded organogel significantly increased transdermal drug delivery in vitro.

Game-theoretic Flux Balance Analysis Model for Predicting Stable Community Composition.

Models for microbial interactions attempt to understand and predict the steady state network of inter-species relationships in a community, e.g. competition for shared metabolites, and cooperation through cross-feeding. Flux balance analysis (FBA) is an approach that was introduced to model the interaction of a particular microbial species with its environment. This approach has been extended to analyzing interactions in a community of microbes; however, these approaches have two important drawbacks: first, one has to numerically solve a differential equationto identify the steady state, and second, there are no methods available to analyze the stability of the steady state. We propose a game theory based community FBA model wherein species compete to maximize their individual growth rate, and the state of the community is given by the resulting Nash equilibrium. We develop a computationally efficient method for directly computing the steady state biomasses and fluxes without solving a differential equation. We also develop a method to determine the stability of a steady state to perturbations in the biomasses and to invasion by new species. We report the results of applying our proposed framework to a small community of four E. coli mutants that compete for externally supplied glucose, as well as cooperate since the mutants are auxotrophic for metabolites exported by other mutants, and a more realistic model for a gut microbiome consisting of nine species.

Research on the characteristics of the Helium plasma beam in HIT-PSI

As a high heat flux linear plasma device designed for studying divertor materials in future fusion reactors, HIT-PSI(Plasma Surface Interaction device at Harbin Institute of Technology) has been successfully constructed and has maintained stable operation since its completion. The characteristics of He plasma beams in HIT-PSI are investigated by emission spectroscopy and an infrared camera, with preliminary irradiation experiments conducted by bombarding tungsten with the beam. For relatively conservative discharge parameters, HIT-PSI achieved a steady-state heat flux capacity of ∼40 MW/m2 using infrared measurements, with the full width at half maximum (FWHM) of the heat flux beam reaching 4 mm. These characteristics make HIT-PSI an advanced platform for testing divertor materials and plasma-facing components, providing essential experimental supports for research and development of high-performance divertor materials.

Experimental investigation and mathematical modelling of a spiral wound membrane module for osmotically assisted reverse osmosis applications

Osmotically assisted reverse osmosis (OARO) has gained interest for applications like desalination, wastewater treatment, and draw solution recovery in forward osmosis. Despite that, on the one hand limited experimental research on pilot- or industrial-scale modules is available, and on the other hand existing simulations are often theoretical and unsuitable for real OARO scenarios. A validated mathematical model reflecting the actual membrane behaviour is crucial for understanding the process accurately and designing it effectively. This study investigated a prototype spiral wound 4040 module for OARO in a pilot plant, using NaCl solutions at various concentrations as feed and sweep solutions. Experiments were carried out at feed concentrations from 17 g/L to 226 g/L and sweep solution concentrations equal to or less than the feed. Steady-state water flux data were collected applying pressures from 8 to 28 bar. In parallel, a predictive mathematical model based on material balances was developed and validated to describe water flux variation within the membrane module, providing insights that are useful for process optimization. Positive water fluxes (1–2 LMH) were obtained even for highly concentrated solutions (226 g/L), indicating the system's capability to handle high salinity feeds. It has been observed that deformation of the membrane under high pressures can adversely affect its performance in a significant way. This is because deformation reduces the cross-sectional area of the membrane and increases the pressure drop on the sweep side. In conclusion, the results demonstrate promising membrane capability in managing high solute concentrations, and the validity of the developed predictive model.

Percutaneous absorption of two bisphenol a analogues, BPAF and TGSA: Novel In vitro data from human skin

Bisphenol AF (BPAF) and TGSA are analogues of Bisphenol A (BPA). BPAF is used in polymer synthesis, while TGSA is applied in thermal papers. The EU classifies BPAF as toxic to reproduction and TGSA as a skin sensitizer. However, TGSA's other health effects remain unclear. BPAF contamination has been noted among electronic waste workers, and TGSA exposure is documented in various professions. Despite the significance of skin contact, data on skin permeation rates for BPAF and TGSA are limited. This study aimed to generate percutaneous absorption data for BPAF and TGSA following OECD guidelines.[14C]-labeled BPAF or TGSA was applied to human skin samples in vitro using Franz diffusion cells for 20 and 40 h, respectively. Key parameters such as steady-state flux, lag time, and skin permeability coefficient (Kp) were calculated. Furthermore, the distribution of the dose across different compartments, particularly within the skin, was evaluated at the conclusion of the experiment. Sequential strippings and epidermis-dermis separation were conducted for BPAF to predict the potential absorption of the remaining dose present within the skin.The permeability coefficients for BPAF and TGSA were found to be 1.9 E−03 and 1.6 E−03 cm/h, with 22% and 23% of the applied doses absorbed, respectively. Both chemicals are classified as "fast" penetrants based on their Kp values. These findings suggest that BPAF and TGSA are absorbed through the skin, highlighting potential occupational risks through dermal exposure. The new percutaneous absorption data will enhance the assessment of the occupational risks.

Application of validated size-exclusion chromatography method for physicochemical characterization of topical gel formulation of deferoxamine conjugated with PEGylated carbon nanoparticles

The focus of current research work was to develop and validate size-exclusion chromatography method and develop and evaluate gel formulation of deferoxamine conjugated with PEGylated carbon nanoparticles (DEF-PEG-CNP) for topical delivery. Size-exclusion chromatography-based method was validated as per ICH guidelines. Effect of Carbopol® 974P and Transcutol® on the nanoparticles’ permeation was studied by 3-level full factorial design of experiment. Gel formulations were characterized for viscosity, cohesive and adhesive force by texture analyzer, and drug permeation through pig ear and human skin. The analytical method was specific as no interference from solvent or excipients were observed and met preset criteria of validation with limit of quantification of 0.24 ± 0.00 μg/mL. The nanoparticles permeation, steady state flux, and retained drug were statistically (p < 0.05) affected by Carbopol® 974P and Transcutol® percentage in the gel formulations. The permeation, steady state flux, and retained nanoparticles from the gel formulations varied from 23.2 ± 2.5 % to 70.9 ± 113.3 %, 0.8 ± 0.3 to 6.6 ± 2.1 μg/cm2.h, and 5.6 ± 0.3 to 38.8 ± 8.8 µg/g, respectively. Permeation of the nanoparticles was 1.9 folds higher in pig skin compared to human skin. Immunofluorescence detected successful permeation of DEF-PEG-CNP particles into skin. In conclusion, the analytical method can quantify the nanoparticles from the gel formulation without interference, and gel formulation of the nanoparticles can permeate across the skin.

Optimization, Formulation, and Ex vivo Evaluation of Solid Lipid Nanoparticles for Transdermal Delivery of Diltiazem Hydrochloride.

Cardiac arrhythmia, is a medical condition that reduces the heart's efficiency in pumping blood, and can be fatal, requires long-term management with conventional drugs, despite their limited efficacy. Diltiazem hydrochloride, chosen as a model drug, has a short biological half-life and extensive metabolism. Administering drug through skin is challenging, particularly due to the penetration via stratum corneum. However, solid lipid nanoparticles as a particulate carrier system can enhance its permeation and bioavailability. The study aimed to develop a matrix type transdermal patch with diltiazem hydrochloride encapsulated in solid lipid nanoparticles Methods: The study used the solvent diffusion technique to prepare SLNs by mixing the drug and solid lipid in an organic phase at 80°C, then slowly adding it to an aqueous phase with continuous stirring for 45 minutes. The resulting nanodispersion was freeze-dried and analyzed for morphological studies, encapsulation efficiency & drug content. A patch was formulated using solvent evaporation technique, incorporating HPMC E50 (2% w/v), propylene glycol, and ethanolic oleic acid (1.5% v/v). SLNs loaded with diltiazem hydrochloride taken equivalent to diltiazem hydrochloride dose in the transdermal patch. The patch was then evaluated for In vitro and skin permeation studies. The result showed a positive correlation between lipid concentration and particle size. Probe sonication and homogenization increased particle size, while stirring speed reduced it. SEM and TEM images confirmed spherical particles with a size of 488.1±4.01nm and an entrapment efficiency of 55.03±1.99%. Drug release studies demonstrated 70.7% drug release from lipid matrix over 24 hrs. The formulated patch with uniform SLN distribution, had a drug content 89.37 ± 0.04% with a surface pH of 6.1 ± 0.53, close to skin pH. The uniformity of content in 3x3 patch estimated to be 14.587 ± 1.404 mg, close to the theoretical content 16.318 ± 1.08 mg, confirmed homogenous distribution of diltiazem hydrochloride SLNs throughout the patch diameter. Cumulative amount released from patch formulation at pH 5.6 and pH 7.4 was 518.1414μg/cm2 and 404.4466 μg/cm2. Synergistic flux enhancement was observed with oleic acid propylene glycol blend. Ex vivo study of the patch showed steady-state flux of 6.9 μg/cm2/hr, permeability coefficient 0.00362 cm/hr, diffusion coefficient 0.000103 cm/hr, cumulative drug permeation (Dmax) 814.885 μg after 24 hrs, and followed a Higuchi-matrix release model. The developed patch possessed improved bioavailability with reduced dosing and enhanced patient compliance.

Aspect-ratio-dependent heat transport by baroclinic acoustic streaming

Standing acoustic waves have been known to generate Eulerian time-mean ‘streaming’ flows at least since the seminal investigation of Lord Rayleigh in the 1880s. Nevertheless, a recent body of numerical and experimental evidence has shown that inhomogeneities in the ambient density distribution lead to much faster flows than arise in classical Rayleigh streaming. The emergence of these unusually strong flows creates new opportunities to enhance heat transfer in systems in which convective cooling cannot otherwise be easily achieved. To assess this possibility, a theoretical study of acoustic streaming in an ideal gas confined in a rectangular channel with top and bottom walls maintained at fixed but differing temperatures is performed. A two time scale system of equations is utilized to efficiently capture the coupling between the fast acoustic waves and the slowly evolving streaming flow, enabling strongly nonlinear regimes to be accessed. A large suite of numerical simulations is carried out to probe the streaming dynamics, to highlight the critical role played by baroclinically generated wave vorticity and to quantify the additional heat flux induced by the standing acoustic wave. Proper treatment of the two-way coupling between the waves and mean flow is found to be essential for convergence to a self-consistent steady state, and the variation of the resulting acoustically enhanced steady-state heat flux with both the amplitude of the acoustic wave and the $O(1)$ aspect ratio of the channel is documented. For certain parameters, heat fluxes almost two orders of magnitude larger than those realizable by conduction alone can be attained.