Permeation Tests Research Articles

Permeability and strength of gradient printed permeable steel manufactured by selective laser melting

Based on the forming principle of laser rapid melting and layered manufacturing, the selective laser melting (SLM) process is suitable for the preparation of permeable metal materials with a certain porosity. One of the important applications of this special structure is the development of permeable steel. In this study, the permeable steel with micron-sized controllable pores was prepared by gradient printing using SLM process. The formation and connectivity mechanism of pore structure were analyzed by adjusting the interlayer arrangement of scanning melt channels, and the influence of process parameters on the pore characteristics, permeability and mechanical properties was systematically investigated. The results revealed that the porosity and pore size of permeable steel were effectively improved by controlling the hatch distance and scanning strategy, with the results ranging from 7.81 % to 17.32 % and 57 μm to 121 μm, respectively. Based on the gas permeation test, it was verified that the permeability of permeable steel showed a clear upward trend with increasing porosity, and the results ranged from 2.17 × 10−12 m2 to 4.26 × 10−12 m2, indicating that the pore structure provides a strong basis for gas flow. Moreover, the mechanical properties of permeable steel decreased significantly with the increase of porosity and pore size, and the compressive strength and tensile strength ranged from 1061 MPa to 528 MPa and 1018 MPa to 609 MPa, respectively. The mechanical behavior and deformation mechanism were closely related to the gradient evolution of the pore structure. Overall, the gradient printed permeable steel using SLM process has good permeability and mechanical properties.

Deuterium permeation performance of V4Cr4Ti/RAFM steel joint with in-situ formed carbide interlayer during diffusion bonding

Vanadium alloy (V4Cr4Ti) is a structural material used in future fusion reactors owing to its inherent advantages of high-temperature strength and neutron irradiation resistance. Oxygen pickup and high hydrogen isotope permeability are the two major concerns for their application in various types of blankets. To solve these issues, a bimetallic joint was designed with a CLF-1 layer of reduced-activation ferritic/martensitic (RAFM) steel to resist corrosion and a CLF-1/V4Cr4Ti bonding interface to suppress hydrogen isotope permeation. Samples were prepared from joints bonded via solid-state diffusion under hot isostatic pressing (HIP). Deuterium (D) gas permeation tests were performed at various temperatures in the range 400–600 °C at 100 kPa. After deuterium permeation tests, the thermal desorption spectra (TDS) of the samples were analyzed. And the permeation behavior of deuterium atom across the joints was schematically discussed. The results showed that bonding with steel could be an effective solution for resisting hydrogen isotope permeation through the V4Cr4Ti alloy. Thermal desorption spectrum (TDS) analysis of the tested samples revealed a desorption peak temperature equivalent to that of TiC. The formation of a 1 µm-wide B2 ordered α'- [Fe, (V, Ti)] phase layer, together with a large number of dispersed carbides around the interface, played a significant role in the deuterium permeation resistance. In addition, microstructural changes in the steel base material after the 900 °C bonding process were beneficial for suppressing deuterium diffusion.

Formulation development of tazarotene-loaded PLGA nanoparticles for follicular delivery in the treatment of inflammatory skin diseases

Tazarotene is a widely prescribed topical retinoid for acne vulgaris and plaque psoriasis and is associated with skin irritation, dryness, flaking, and photosensitivity. In vitro permeation of tazarotene was studied across the dermatomed human and full-thickness porcine skin. The conversion of tazarotene to the active form tazarotenic acid was studied in various skin models. Tazarotene-loaded PLGA nanoparticles were prepared using the nanoprecipitation technique to target skin and hair follicles effectively. The effect of formulation and processing variables on nanoparticle properties, such as particle size and drug loading, was investigated. The optimized nanoparticle batches with particle size <500 µm were characterized further for FT-IR analysis, which indicated no interactions between tazarotene and PLGA. Scanning electron microscopy analysis showed uniform, spherical, and non-agglomerated nanoparticles. In vitro release study using a dialysis membrane indicated a sustained release of 40–70 % for different batches over 36 h, following a diffusion-based release mechanism based on the Higuchi model. In vitro permeation testing (IVPT) in full-thickness porcine skin showed significantly enhanced follicular and skin delivery from nanoparticles compared to solution. The presence of tazarotenic acid in the skin from tazarotene nanoparticles indicated the effectiveness of nanoparticle formulations in retaining bioconversion ability and targeting follicular delivery.

A multi-layer model for double-skin Pd-based membranes: Layer-by-layer parameter fitting

The Pd-based double-skin (DS) membrane has high potential to be implemented in various industrial processes. However, its multi-layer structure makes it difficult to model and understand the limiting transport mechanisms through each of these layers. In this work an extensive set of experiments on several membranes with different configurations was performed with the purpose of deriving a detailed model for the double-skin Pd-based membrane. This is important for the general understanding of the mass-transport taking place within each of the membrane layers, namely the support, the selective and the protective layer. Characterization, permeation tests and data-fitting led to the construction and validation of a multi-layer model for the DS-membrane. The experimental results also pointed out that the protective layer of HT or YSZ/Al2O3 has only a minor or negligible effect on the overall transport resistance of the membrane. The influence of the support was found to be small but not negligible compared to the dominating resistance of the dense selective PdAg layer. Experiments and simulations of the membrane permeation in multi-component mixtures also highlighted the large importance of concentration polarization and H2 depletion, which were successfully described in the model using a film-layer model together with a Sherwood correlation.

Development of 4-phenylbutyric acid microsponge gel formulations for the treatment of lewisite-mediated skin injury.

Lewisite, a chemical warfare agent, causes skin blisters, erythema, edema, and inflammation, requiring mitigation strategies in case of accidental or deliberate exposure. 4-phenyl butyric acid (4-PBA), a chemical chaperone, reduces endoplasmic reticulum stress and skin inflammation. The study aimed to encapsulate 4-PBA in microsponges for effective, sustained delivery against lewisite injury. Porous microsponges in a topical gel would potentially sustain delivery and improve residence time on the skin. Microsponges were developed using the quasi-emulsion solvent diffusion method with Eudragit RS100. Optimized formulation showed 10.58%w/w drug loading was incorporated in a carboxymethylcellulose (CMC) and Carbopol gel for in vitro release and permeation testing using dermatomed human skin. A sustained release was obtained from all vehicles in the release study, and IVPT results showed that compared to the control (41.52 ± 2.54µg/sq.cm), a sustained permeation profile with a reduced delivery was observed for microsponges in PBS (14.16 ± 1.23µg/sq.cm) along with Carbopol 980 gel (12.55 ± 1.41µg/sq.cm), and CMC gel (10.09 ± 1.23µg/sq.cm) at 24h. Optimized formulation showed significant protection against lewisite surrogate phenyl arsine oxide (PAO) challenged skin injury in Ptch1+/-/SKH-1 hairless mice at gross and molecular levels. A reduction in Draize score by 29%, a reduction in skin bifold thickness by 8%, a significant reduction in levels of IL-1β, IL6, and GM-CSF by 54%, 30%, and 55%, respectively, and a reduction in apoptosis by 31% was observed. Thus, the translational feasibility of 4-PBA microsponges for effective, sustained delivery against lewisite skin injury is demonstrated.

Influence of welding defects on hydrogen embrittlement sensitivity of girth welds in X80 pipelines

Hydrogen embrittlement poses a considerable threat to girth welds in high-grade steel pipelines. This study investigated the influence of welding defects on the hydrogen embrittlement sensitivity of girth welds in X80 pipelines through slow strain rate tensile (SSRT) testing, scanning electron microscopy, hydrogen permeation test, and finite element analysis. The findings indicated that regardless of the presence of welding defects, the hydrogen embrittlement sensitivity of pipeline girth welds increases with negative current density. Welding defects can lead to a substantial increase in the hydrogen embrittlement sensitivity of girth welds and can shift crack initiation points from the surface areas of SSRT specimens to the locations of the defects. Stress concentration caused by welding defects results in the redistribution and local enrichment of hydrogen under the effect of stress-induced hydrogen diffusion, thereby leading to a considerable increase in hydrogen embrittlement sensitivity.

Molecular design of free volume structure in thermally rearranged polybenzoxazole membranes for gas separation studied by positron annihilation

AbstractIn this work, 2,2‐bis(3‐amino‐4‐hydroxyphenyl) hexafluoropropane (APAF) was used as the fixed diamine monomer, and 4,4′‐(hexafluoroisopropylidene) diphthalic anhydride (6FDA), 4,4′‐oxydiphthalic anhydride (ODPA), 3,3′,4,4′‐biphenyltetracarboxylic diandhydride (BPDA) and pyromellitic dianhydride (PMDA) were selected as four different dianhydride monomers, respectively, to prepare the thermally rearranged polybenzoxazole (TR‐PBO) gas separation membranes with different structures via a thermal rearrangement reaction at 450°C. The microstructure of TR‐PBO membranes was investigated using X‐ray diffraction and positron annihilation spectroscopy. All the TR‐PBO membranes exhibit bimodal free volume structure, containing ultramicropores (&lt;0.7 nm) and micropores (&lt;2 nm) with size of 3.6–4.6 and 7.6–8.4 Å, respectively. As the steric hindrance of the bridging groups in the dianhydride monomers increases, the radius and number of pores in the membranes increases, leading to an increase in fractional free volume (FFV). The pure gas permeation test shows a positive correlation between gas permeability and FFV in the TR‐PBO membranes, indicating that an increase in FFV is favorable for the diffusion of gas molecules. Particularly, the ultramicropores play a decisive role on the gas selectivity. All the TR‐PBO membranes exhibit excellent gas permeaselectivity. Among them, the H2/CH4 separation performance of APAF‐6FDA and APAF‐ODPA membranes approaches the 2008 Robeson upper bound, which is due to the high number of both micropores and ultramicropores. Our results demonstrate that the free volume structure of polymer membranes can be designed by selecting monomers with different structures and utilizing thermal rearrangement reactions, allowing for the preparation of gas separation membranes with high permeability and selectivity.

Unveiling the roles of initial phase constituents and phase metastability in hydrogen embrittlement of TRIP‐assisted VCrCoFeNi medium‐entropy alloys

Medium-entropy alloys (MEAs) that exhibit transformation-induced plasticity (TRIP) from face-centered cubic (FCC) to body-centered cubic (BCC) are considered promising for liquid hydrogen environments due to their remarkable cryogenic strength. Nonetheless, studies on hydrogen embrittlement (HE) in BCC-TRIP MEAs have not been conducted, although the TRIP effect and consequent BCC martensite usually deteriorate HE susceptibility. In these alloys, initial as-quenched martensite alters hydrogen diffusion and trap behavior, and deformation-induced martensitic transformation (DIMT) provides preferred crack propagation sites, which critically affects HE susceptibility. Therefore, this study aims to investigate the HE behavior of BCC-TRIP MEAs by designing four V10Cr10Co30Fe50–xNix (x = 0, 1, 2, and 3 at%) MEAs, adjusting both the initial phase constituent and phase metastability. A decreased Ni content leads to a reduced fraction and mechanical stability of FCC, which in turn increases HE susceptibility, as determined through electrochemical hydrogen pre-charging and slow-strain rate tests The permeation test and thermal desorption analysis reveal that the hydrogen diffusivity and content are affected by initial BCC fraction, interconnectivity of BCC, and refined FCC. As these initial phase constituents differ between the alloys with FCC- and BCC- dominant initial phase, microstructural factors affecting HE are unveiled discretely among these alloy groups by correlation of hydrogen-induced crack behavior with hydrogen diffusion and trap behavior. In alloys with an FCC-dominant initial phase, the initial BCC fraction and DIMT initiation rate emerge as critical factors, rather than the extent of DIMT. For BCC-dominant alloys, the primary contributor is an increase in the initial BCC fraction, rather than the extent or rate of DIMT. The unraveled roles of microstructural factors provide insights into designing HE-resistant BCC-TRIP MEAs.

Observations on the Tritiated Water and TEWL Skin Integrity Tests: Relevance to In Vitro Permeation Testing (IVPT).

The in vitro permeation test (IVPT) using ex vivo human skin is a sensitive and robust model system that has been vital in elucidating the fundamental parameters surrounding the absorption of both therapeutic agents and industrial chemicals through skin. FDA and OECD IVPT Guidances recommend that each skin section selected for study should be screened prior to use to ensure that the stratum corneum integrity is retained. Three methods are currently considered acceptable: 1) transepidermal water loss (TEWL), 2) electrical resistance, and 3) tritiated water (3H2O) absorption. A retrospective analysis of data from the authors' laboratory has been performed with the objective of addressing a number of questions regarding the 3H2O and TEWL integrity tests, and the population attributes of a large database consisting of 17,330 individual skin sections obtained from 459 skin donors. The applicability and usefulness of these tests, when compared to companion permeation data obtained from 25 topical drug products, has also been examined. Both integrity tests found water permeability to be equal in White and Hispanic races but higher than in Blacks, 3H2O being more discriminating than TEWL. Male skin is more permeable than female and there is a slight decrease in permeability with advancing age in both groups. Correlation between 3H2O absorption and drug absorption revealed a minimal relationship between the two in most cases, the Pearson correlation coefficient ranging from -0.417 to 0.953. Additionally, drug outliers were not always identified with a failing integrity test. The results call for a critical reexamination of the value of the 3H2O integrity test, and by extension, TEWL, for use in IVPT studies.

Modelling of room temperature outgassing and diffusion in a martensitic advanced high-strength steel

Hydrogen embrittlement (HE) is among the limiting factors for the employment of advanced high-strength steels in the automotive industry. One of the most relevant manifestations of HE for those components is delayed fracture. To perform HE risk assessment against delayed fracture in structural components wherein hydrogen accumulates near notches or bends after manufacturing or assembly, continuum models can be used to predict hydrogen diffusion and accumulation. To this aim, it is crucial to identify both the correct model parameters and boundary conditions (BCs). This study provides the required modelling and experimental framework to estimate the constitutive diffusion, trapping and outgassing parameters for a commercial martensitic advanced high-strength steel grade 1300. Permeation testing and simple room outgassing tests showed that a natural BC with one-parameter effectively reproduces the experimental results. The proposed model can be used to predict a reasonable hydrogen distribution, both inside of the component and near to the surface, which is valuable for HE risk assessments. Finally, the same BC can be employed with the interpretation of ex-situ hydrogen charged tensile tests.

Design, preparation and diffusion research of the W coating used in W-based cermet for nuclear thermal propulsion

The fissile fuel agglomeration and loss in the tungsten (W) based ceramic-metallic (cermet) fuel element are the major challenges for application in nuclear thermal propulsion (NTP). The previous research indicated that a W coating deposited on the surface of uranium dioxide (UO2) by the fluidized bed chemical vapor deposition (CVD) technique is an efficient way to achieve the uniform distribution of fuel particles and reduce fuel loss simultaneously. However, the W layers' resulting thicknesses differ, which is not conducive to achieving high fuel loading. Therefore, in this study, the appropriate thickness of the W coating is first investigated by COMSOL Multiphysics modeling. Through contrastive analyses, the W layer with a thickness of about 5–10 μm is considered to be the optimal choice, where the maximum loading capacity of the fissile fuel can be achieved with a volume fraction of about 60%. Based on the above calculations, the CVD technique is employed to produce the optimized thickness of the W layer by precisely adjusting the deposition time at 900 °C. This approach is taken after determining the critical influencing factor that governs the performance of the W layer. Experimental results show that the highly dense W layer presents a uniform thickness and fine-grained size. As the only structural and protective layer, the application of this W coating provides a barrier for blocking the inward diffusion of hydrogen (H2) to stop the detrimental chemical reactions between UO2 and H2, thus lowering fuel loss. The spark plasma sintering (SPS) demonstrates that zirconium dioxide (ZrO2) particles as the surrogate for UO2 exhibit a homogeneous distribution without any direct contact in the W matrix because of the presence of the W coating. Despite the fact that the interface between the W coating and the W matrix exhibits remarkable bonding, making it difficult to clearly discern the boundaries due to surface diffusion and atomic binding, the existence and integrity of the W coating after high-temperature sintering is unequivocally confirmed through interface TEM observations and the uniform dispersion of coated particles within the W-Y2O3 matrix. Furthermore, the fine-grained W coating has been demonstrated to effectively hinder the diffusion of H2 isotopes through permeation and diffusion tests. This comprehensive study not only aids in establishing the optimal geometrical thickness for the W coating but also underscores its pivotal role in W-based cermet fuels for NTP system.

Integrated Janus nanofibers enabled by a co-shell solvent for enhancing icariin delivery efficiency

During the past several decades, nanostructures have played their increasing influences on the developments of novel nano drug delivery systems, among which, double-chamber Janus nanostructure is a popular one. In this study, a new tri-channel spinneret was developed, in which two parallel metal capillaries were nested into another metal capillary in a core–shell manner. A tri-fluid electrospinning was conducted with a solvent mixture as the shell working fluid for ensuring the formation of an integrated Janus nanostructure. The scanning electronic microscopic results demonstrated that the resultant nanofibers had a linear morphology and two distinct compartments within them, as indicated by the image of a cross-section. Fourier Transformation Infra-Red spectra and X-Ray Diffraction patterns verified that the loaded poorly water-soluble drug, i.e. icariin, presented in the Janus medicated nanofibers in an amorphous state, which should be attributed to the favorable secondary interactions between icariin and the two soluble polymeric matrices, i.e. hydroxypropyl methyl cellulose (HPMC) and polyvinylpyrrolidone (PVP). The in vitro dissolution tests revealed that icariin, when encapsulated within the Janus nanofibers, exhibited complete release within a duration of 5 min, which was over 11 times faster compared to the raw drug particles. Furthermore, the ex vivo permeation tests demonstrated that the permeation rate of icariin was 16.2 times higher than that of the drug powders. This improvement was attributed to both the rapid dissolution of the drug and the pre-release of the trans-membrane enhancer sodium lauryl sulfate from the PVP side of the nanofibers. Mechanisms for microformation, drug release, and permeation were proposed. Based on the methodologies outlined in this study, numerous novel Janus nanostructure-based nano drug delivery systems can be developed for poorly water-soluble drugs in the future.

Trilayer dissolving microneedle for transdermal delivery of minoxidil: a proof-of-concept study

Alopecia areata (AA) is a chronic autoimmune disease characterized by bald patches in certain areas of the body, especially the scalp. Minoxidil (MNX), as a first-line treatment of AA, effectively induces hair growth. However, oral and topical administration pose problems, including low bioavailability, risk of uncontrolled hair growth, and local side effects such as burning hair loss, and scalp irritation. In the latest research, MNX was delivered to the skin via microneedle (MN) transdermally. The MNX concentration was distributed throughout the needle so that drug penetration was reduced and had the potential to irritate. In this study, we formulated MNX into three-layer dissolving microneedles (TDMN) to increase drug penetration and avoid irritation. Physicochemical evaluation, parafilm, was used to evaluate the mechanical strength of TDMN and showed that TDMN could penetrate the stratum corneum. The ex-vivo permeation test showed that the highest average permeation result was obtained for TDMN2, namely 165.28 ± 31.87 ug/cm2, while for Minoxidil cream it was 46.03 ± 8.5 ug/cm2. The results of ex vivo and in vivo dermatokinetic tests showed that the amount of drug concentration remaining in the skin from the TDMN2 formula was higher compared to the cream preparation. The formula developed has no potential for irritation and toxicity based on the HET-CAM test and hemolysis test. TDMN is a promising alternative to administering MNX to overcome MNX problems and increase the effectiveness of AA therapy.

Evaluation of the “nickel effect” in sulfide stress cracking of low alloy steels

The “nickel effect” refers to the cause of the 1 wt %Ni maximum limit in low alloy steels for the oil and gas production industry to avoid sulfide stress cracking (SSC). The Ni restriction dates to the first edition of the NACE MR 0175/ISO 15156 standard in 1975 and the specific reasons for that limitation remain disputed. This work evaluates the nickel effect with electrochemical tests in the presence and absence of tensile loads at anodic and cathodic potentials and at the open circuit potential (OCP). Thiosulfate was used as a satisfactory alternative to H2S bubbling. The effect of nickel on hydrogen transport and trapping was analyzed with gaseous hydrogen permeation tests. A strong influence of Ni, even at Ni contents below 1 wt%, on SSC initiation at OCP due to trench formation was observed. Compared to other common alloying elements, Ni had a modest role in hydrogen trapping.

Specific delivery of metronidazole using microparticles and thermosensitive in situ hydrogel for intrapocket administration as an alternative in periodontitis treatment

Periodontitis is a common chronic inflammatory disease primarily caused by the prevalence of bacterial overgrowth resulting in the development of an inflammatory condition that destroys the tooth’s supporting tissues and eventual tooth loss. Comparatively, to other treatment methods, it is difficult for topical antibacterial drugs to effectively permeate the biofilm’s physical barrier, making conventional therapy for periodontitis more challenging. This novel study combines thermosensitive in situ hydrogel with microparticles (MPs) to enhance the targeted delivery of metronidazole (MET) to the periodontal pocket. Polycaprolactone (PCL) polymer was utilized to produce bacteria-sensitive MPs. Additionally, the study assessed the attributes of MPs and demonstrated an enhancement in the in vitro antibacterial efficacy of MPs towards Staphylococcus aureus (SA) and Escherichia coli (EC). Subsequently, we incorporated MET-MPs into thermosensitive in situ hydrogel formulations using chitosan. The optimized formulations exhibited stability, appropriate gelation temperature, mucoadhesive strength, and viscosity. In vitro permeation tests showed selective and prolonged drug release against SA and EC. Ex vivo experiments demonstrated no significant differences between in situ hydrogel containing pure MET and MET–MPs in biofilm quantity, bacterial counts, and metabolic activity in biofilms. According to in vitro tests and the effectiveness of the antibacterial activity, this study has exhibited a novel methodology for more efficacious therapies for periodontitis. This study aims to utilize MET in MPs to improve its effectiveness, enhance its antibacterial activity, and improve patient treatment outcomes. In further research, the efficacy of the treatment should be investigated in vivo using an appropriate animal model.

The influence of the experimental methodology on evaluating the hydrogen embrittlement susceptibility of AISI 4340 steel manufactured by different routes

High strength low alloy steels are widely used in the offshore and marine industries for the manufacturing of fasteners. In this context, the occurrence of hydrogen embrittlement is a risk to the service life of these components. The scope of this work is to evaluate the impact of the steelmaking process on the hydrogen embrittlement susceptibility of AISI 4340 steel through different experimental methodologies. The effects of the presence of segregation bands and inclusions on the hydrogen interaction with the microstructure of the steel were studied through hydrogen electrochemical permeation tests and mechanical characterization. The hydrogen embrittlement susceptibility was investigated by performing uniaxial standard tensile tests with prior hydrogen charging, slow strain rate tests with in-situ hydrogen charging, and incremental step loading tests with notched specimens and in-situ hydrogen charging. Fractographic analyzes were carried out to support the interpretation and discussion of the results. It was observed that continuous casting route results in a microstructure more susceptible to hydrogen embrittlement, due to the presence of coarser segregation bands, with a greater density of impurities and inclusions.

ROS-Responsive PLGA-NPs for Co-Delivery of DTX and DHA for Colon Cancer Treatment

The aim of this work was to evaluate the antineoplastic effect of newly synthesized nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) alone or PLGA esterified with 2,2′-[propane-2,2-diylbis (thio)] diacetic acid (TKL), loaded with docetaxel (DTX) and/or docosahexaenoic acid (DHA), as innovative site-specific therapeutic carriers. The obtained materials were characterized by FT-IR and 1H-NMR, while the dimensional analysis of the nanoparticles obtained was performed by Dynamic Light Scattering. The encapsulation efficiency of the nanoparticles was evaluated, and in vitro skin permeation tests were also performed. The antitumor activity of the nanomaterial was studied in the human adenocarcinoma HCT116 cell line. In particular, viability tests in bidimensional culture, as well as in tumor spheroids, were conducted. The use of these nanocarriers could facilitate the stable and efficient delivery of DTX and DHA through the upper segments of the gastrointestinal tract to the colon. In addition, the presence of the ROS-sensitive 2,2′-[propane-2,2-diylbis (thio)] diacetic acid in their matrix should promote the site-specific release of DTX in the tumor mass, where high levels of reactive oxygen species could be found.

QbD Based Formulation Development and Optimisation of Ozenoxacin Topical Nano-Emulgel and Efficacy Evaluation Using Impetigo Mice Model.

To formulate and optimize Ozenoxacin nano-emulsion using Quality by Design (QbD) concept by means of Box-Behnken Design (BBD) and converting it to a gel to form Ozenoxacin nano-emulgel followed by physico-chemical, in-vitro, ex-vivo and in-vivo evaluation. This study demonstrates the application of QbD methodology for the development and optimization of an effective topical nanoemulgel formulation for the treatment of Impetigo focusing on the selection of appropriate excipients, optimization of formulation and process variables, and characterization of critical quality attributes. BBD was used to study the effect of "% of oil, % of Smix and homogenization speed" on critical quality attributes "globule size and % entrapment efficiency" for the optimisation of Ozenoxacin Nano-emulsion. Ozenoxacin loaded nano-emulgel was characterized for "description, identification, pH, specific gravity, amplitude sweep, viscosity, assay, organic impurities, antimicrobial effectiveness testing, in-vitro release testing, ex-vivo permeation testing, skin retention and in-vivo anti-bacterial activity". In-vitro release and ex-vivo permeation, skin retention and in-vivo anti-bacterial activity were found to be significantly (p < 0.01) higher for the nano-emulgel formulation compared to the innovator formulation (OZANEX™). Antimicrobial effectiveness testing was performed and found that even at 70% label claim of benzoic acid is effective to inhibit microbial growth in the drug product. The systematic application of QbD principles facilitated the successful development and optimization of a Ozenoxacin Nano-Emulsion. Optimised Ozenoxacin Nano-Emulgel can be considered as an effective alternative and found to be stable at least for 6months at 40°C / 75% RH and 30°C / 75% RH.

A strong, silk protein-inspired tissue adhesive with an enhanced drug release mechanism for transdermal drug delivery

In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu2+ adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu2+ to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu2+-p-π conjugated network in PHT-SP-Cu2+ were characterized and elucidated using different characterization methods including FT-IR, 13C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu2+ provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu2+ was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87–4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu2+ could adhere to the human body for more than six days. Moreover, the drug loading, in vitro release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu2+ had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu2+ was increased by 6.25-fold compared with PHT, and in the in vivo pharmacokinetic analysis, the AUC was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu2+ for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency. Statement of significanceA new adhesive, PHT-SP-Cu2+, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu2+ were used in synthesis. Characterization techniques confirmed the structure and Cu2+-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu2+, exhibiting superior adhesion. PHT-SP-Cu2+ showed 7.6 times higher peel strength than DURO-TAK® 87–4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher AUC in vivo studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu2+ showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches.

Recognition and separation of artemisinin by two-dimensional GO/MXene laminar imprinted composite membranes constructed based on self-supporting technology

In order to solve the problem that some of the imprinted sites were embedded inside the membranes due to the blending method, resulting in low utilization of the imprinted sites, a two-dimensional click graphene oxide (GO)/MXene self-supported layered imprinted composite membranes (CGMMs) was devised and prepared for the adsorption and efficient discriminative separation of artemisinin. Firstly, MXene was modified by self-polymerization using dopamine (PDA), and PDA hybrid coating was constructed on the surface of MXene, which was effective in improving the oxidation brittleness and hydrophilicity of MXene. Given the structural and hydrophilic similarities between GO and MXene nanosheets, the produced CGMMs exhibit an outstanding hydrophilicity and a characteristic lamellar shape. Subsequently, spherical imprinted polymers based on MXene were successfully constructed on the surface and interlayer of stacked GO/MXene nanosheets. The performance of CGMMs was explored by isothermal adsorption, kinetic adsorption, selective adsorption tests and selective permeation tests. The equilibrium adsorption capacity of CGMMs reached 36.10 mg g−1 with satisfactory selective separation capacity (αArtemisinin/ Artesunate = 4.10 and αArtemisinin/ Dihydroartemisinin = 3.03) and excellent permeation selectivity (βArtesunate/ Artemisinin = 5.71 and βDihydroartemisinin/ Artemisinin = 4.40), which implied the successful construction of effective artemisinin-imprinted sites on CGMMs. An essential aspect of the excellent adsorption property and selectivity exhibited by the prepared CGMMs is that the cross-section of CGMMs is composed of MXene nanosheets and GO nanosheets superimposed on a laminar structure dotted with imprinted polymers, which extends the molecular transport channels and facilitates the construction of more molecular imprinting sites.