Pseudo-ternary Phase Diagrams Research Articles

Pseudoternary Phase Diagram and Antibacterial Activity of Microemulsion-Based Citronella Oil

Citronella oil (CTO) is extracted from citronella leaves by maceration or steam distillation process, which has antibacterial and insect-repellent activities. However, the use of CTO is limited and requires modification in other formulations, such as microemulsion (ME), to increase its bioactivities. ME consists of oil, water, surfactant and/or cosurfactant and is commonly applied in food and beverages, cosmetics, and carrier for drug delivery applications. CTO was used as the oil phase for ME with nonionic surfactant and ethanol as a cosurfactant for lowering interfacial tension between oil and water phase. Subsequent observations regarding stability and antibacterial tests were carried out on ME formulations with surfactant/cosurfactant mixture of 2 due to its largest ME area. A hydrodynamic diameter analysis was also carried out to see the stability of the ME within a period of 50 d. ME with 10% CTO, 30% surfactant mixture, and 60% water showed the best formulation observed from the consistent hydrodynamic diameter measurement. In addition, ME with different formulations could inhibit the growth of Escherichia coli and Staphylococcus aureus by more than 90%. From this research, CTO-based ME potentially improve and develop drug carrier applications, especially via topical route.

Redox-switchable microemulsions with efficient phase separation and surfactant recycling

HypothesisSwitchable microemulsions (MEs) are those capable of adaptively responding to the action of internal or external stimuli. For redox-switchable MEs to obtain high-efficiency phase separation and surfactant recycling, it may be one of the keys to adequately turn off the interfacial activity of surfactants and reduce the solubility of the closed surfactants in the oil phase. ExperimentsMonophasic MEs consisting 11-butylselanyl-undecyl sulfate sodium (C4SeC11SO4Na), n-butanol, n-octane, and water were fabricated using the pseudo-ternary phase diagram method. Their structural features and droplets size were characterized by conductivity, dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM), respectively. The redox response of MEs was studied using a combination of visual observations and DLS, cryo-TEM, nuclear magnetic resonance (NMR) and thin-layer tomography. The efficient recycling of C4SeC11SO4Na from a well-emulsified eluent is conceptually demonstrated. FindingsThe reversible transition between C4SeC11SO4Na and C4SeOC11SO4Na is achieved under the alternating action of H2O2 and N2H4, by which C4SeC11SO4Na-based monophasic MEs are able to efficiently demulsify and regenerate, respectively, regardless of their type. After H2O2-induced demulsification of the MEs, C4SeOC11SO4Na can be efficiently recycled with the water phase. We hope that such a redox-switching method may benefit some technological applications. For example, it offers exciting possibilities for simultaneous recycling C4SeC11SO4Na and removal of oil from a well-emulsified eluent. Around 97.1 ± 0.3 % of C4SeC11SO4Na could be recycled over five cycles with no apparent loss. After a simple and conventional treatment with anion-exchange resin and active carbon, the total organic carbon and chemical oxygen demand of the waste water were 17.4 ± 2.8 and 26.2 ± 1.4 mg/L, respectively.

Development and Characterization of a Microemulsion Containing a Cannabidiol Oil and a Hydrophilic Extract from Sambucus ebulus for Topical Administration.

Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with potential anti-inflammatory and antioxidant activity for the topical treatment of inflammatory skin disorders. The microemulsion system was composed of a 20% CBD oil, which served as the hydrophobic phase; Labrasol/Plurol Oleique (1:1), which served as surfactant and cosurfactant (S/CoS), respectively; and an aqueous vegetal extract obtained from Sambucus ebulus L. (S. ebulus) ripe fruits, which has potential anti-oxidant and anti-inflammatory activity and which served as the aqueous phase. A pseudo-ternary phase diagram was generated, leading to the selection of an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after its reproducibility was tested, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size (by laser scattering), compatibility of components (by differential scanning calorimetry) and rheological properties (using a rotational rheometer). The designed microemulsion showed good stability and slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the aqueous phase of the microemulsion were studied via in vitro diffusion experiments using flow-through diffusion cells and were compared to those of a CBD oil and a microemulsion containing only CBD as an active substance. It was found that the inclusion of the original oil in microemulsions did not result in a significant modification of the release of CBD, suggesting the possibility of including hydrophilic active compounds in the formulation and establishing an interesting strategy for the development of future formulations.

Fabrication and characterization of transdermal delivery of ribociclib nanoemulgel in breast cancer treatment.

The objective of this study is to create a nanoemulgel formulation of Ribociclib (RIBO), a highly selective inhibitor of CDK4/6 through the utilization of spontaneous emulsification method. An experimental investigation was conducted to construct pseudo-ternary phase diagram for the most favourable formulation utilizing rice bran oil, which is known for its diverse anticancer properties. The formulation consisted of varying combination of the surfactant and as the co-surfactant (Tween 80 and Transcutol, respectively) referred to as Smix and the trials were optimized to get the desired outcome. The nanoemulsion (NE) formulations that were developed exhibited a droplet size of 179.39 nm, accompanied with a PDI of 0.211. According to the data released by Opt-RIBO-NE, it can be inferred that the Higuchi model had the most favourable fit among many kinetics models considered. The results indicate that the use of nanogel preparations for the topical delivery of RIBO in breast cancer therapy, specifically RIBO-NE-G, is viable. This is supported by the extended release of the RIBO, and the appropriate level of drug permeation observed in Opt-RIBO-NE-G. Due to RIBO and Rice Bran oil, RIBO-NE-G had greater antioxidant activity, indicating its effectiveness as antioxidants. The stability of the RIBO-NE-G was observed over a period of three months, indicating a favourable shelf life. Therefore, this study proposes the utilization of an optimized formulation of RIBO-NE-G may enhance the efficacy of anticancer treatment and mitigate the occurrence of systemic side effects in breast cancer patients, as compared to the use of suspension preparation of RIBO.

Water in nigella oil microemulsion for enhanced oral bioavailability of linagliptin.

Linagliptin is hydrophilic antidiabetic with poor oral bioavailability due to poor permeability and pre-systemic metabolism. The objective was to assess w/o microemulsion for enhanced oral bioavailability of linagliptin. Nigella oil was used as oily phase based on its reported antidiabetic effect. Isopropyl myristate (IPM) or capryol were combined with nigella oil to impart intestinal membrane permeabilizing abilities. Pseudoternary phase diagrams were constructed utilizing nigella oil in presence and absence of isopropyl myristate or capryol as oily phase using Tween 60 as surfactant. W/O microemulsion formulations were selected from the constructed phase diagrams and linagliptin was loaded in the internal aqueous phase at a concentration of 0.5mg/ml. The prepared formulations were physically evaluated and linagliptin in vitro release was monitored. Eventually, the in vivo hypoglycemic effect was assessed using diabetic rats. The developed microemulsions were of w/o type and exhibited Newtonian flow behavior with nigella/capryol microemulsion recording the lowest viscosity. The recorded droplet size values were 104.9, 121.2 and 86.4nm for nigella, nigella/IPM and nigella/capryol microemulsions, respectively. All microemulsion formulations showed slower drug release rate compared with aqueous suspension with nigella/capryol microemulsion showing the highest release rate compared to other microemulsions. Release data from microemulsion best fitted to Higuchi model. In vivo oral hypoglycemic activity measurement reflected a more intensified hypoglycemic effect with rapid onset after oral ingestion of microemulsion compared to linagliptin dispersion. Nigella oil/IPM-based microemulsion was ranked as the most effective. The investigation highlighted the feasibility of w/o microemulsion for enhanced oral bioavailability of hydrophilic drugs like linagliptin.

Melting and Flow Behavior of Coal Ash at High Temperatures Based on SiO2-Al2O3-CaO/Na2O Pseudoternary Phase Diagram.

The entrained-flow gasifier has a better adaptability to various coals. The composition of coal ash is an important factor affecting the high-temperature flow characteristics of molten slag. Based on the SiO2-Al2O3-CaO/Na2O ternary phase diagram, the high-temperature molten flow characteristics of slag located in the main phase regions of feldspar, melilite, diopside, and mullite were investigated by experiments and thermodynamic software calculations. The results indicate that the melting process of ash in the three phase zones is influenced by different factors. It was discovered by infrared spectroscopy analysis that the slag was dominated by Si2O52- ion clusters in the feldspar region. The slag in the diopside region had a slightly higher proportion of simple silicate ion clusters than the slag in the feldspar region, resulting in better fluidity. This is significant for revealing the mechanism of coal ash melting and flowing and guiding industrial coal blending.

PREPARATION AND EVALUATION OF LAFUTIDINE NANOEMULSION AS ORAL DELIVERY SYSTEM

Objective: Lafutidine is a histamine (H2) receptor antagonist utilized for the treatment of gastric ulcer. Its oral bioavailability is low due to poor water solubility and an extensive first-pass hepatic. So, the present work aims to formulate and characterize of an oil in water (o/w) nanoemulsion of lafutidine as oral liquid dosage form and this could enhance drug solubility and improve its bioavailability. Methods: The pseudo-ternary phase diagrams were constructed via titration method. The diagram plots derived from oil, various ratios of surfactant and co-surfactant (S mix), and double distilled water. The selected optimized lafutidine nanoemulsions formula was determined via a variety of investigational studies like particle size, polydispersity index (PDI), zeta potential, pH, drug content and an in vitro drug release. Results: Characterization studies revealed that the optimum formula of nanoemulsions was (NE5), which consist of 0.2% of lafutidine, 30 % of surfactant and co-surfactant (S mix) (3:1), which mean (22.5%of tween 20:7.5% of polyethylene glycol 200 (PEG 200), 10% of peppermint oil and 59.4% of double distilled water. The optimized formula exhibited droplets size (62.56-96.2 nm), PDI (0.11), good pH value (7.1), zeta potential (-32.2 mV), high drug content (99.2%), in vitro release of lafutidine was significantly higher (P<0.05) for NE5. Scanning probe microscopy (SPM) revealed that the droplets size of NE5 was in nano-scale. Conclusion: It is possible to conclude that the optimized formula (NE5) was promised formula of nanoemulsion for increasing the orally delivered lafutidine bioavailability.

Nanoemulsion based in-situ Gel for Ocular Delivery of Brimonidine Tartrate

Background: Brimonidine tartrate is currently used to treat glaucoma; however, conventional ocular formulations have some disadvantages in terms of treating disorders like glaucoma, as less than 5% of the drug reaches a posterior segment of the eye; hence, there is a need for sustained treatment. Objective: The objective of this study was to develop a self-nanoemulsion (SNEDDS) in-situ gel of brimonidine tartrate to investigate the sustained-release effect to improve ocular bioavailability. Method: Oil, surfactant, and co-surfactant were screened using the pseudo-ternary phase diagram (TPD) by aqueous-titration method based on the drug solubility. Nanoemulsions were evaluated for the pH, viscosity, % drug content, % transmittance, dispersibility, particle size, zeta-potential, TEM, and conductivity test. Nanoemulsion was incorporated into in-situ gel and evaluated for gelling capacity, pourability, gel strength, in vitro drug release study, and drug release kinetics. Result: Castor oil (10%) as oil phase, Acrysol K-140 (10%) as surfactant, and PEG 400 (20%) as cosurfactant were selected in preparation of SNEDDS from TPD. Evaluation parameters of SNEDDS were found in an acceptable range. % Drug release showed the controlled release up to 8 hrs. Optimum % drug content and % CDR were 100.25% and 92.46% after 12hrs, respectively. Optimized SNEDDS in-situ gel followed the Higuchi model via diffusion mechanism having 0.99 R² value and exhibiting sustained release up to 12 hr. Stability study proved no significant changes during storage. In vitro, the ocular irritancy test proved suitable for ocular delivery. Conclusion: A sustained-release formulation was obtained by developing brimonidine tartrate SNEDDS in-situ gel as a stable formulation without irritancy during ocular administration.

Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin.

The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified through the water titration method and pseudoternary phase diagram plots. The interfacial tension between caprylic/capric triglyceride (CCT oil) and water was significantly reduced by the surfactant/co-surfactant combination (Smix) of Cremophore® RH40 and a double-tails co-surfactant, polyglycerol-3-diisostearate, at an HLB of 13 together with a water-to-co-solvent (PG) ratio of 1:1. A two-level full factorial design of experiment (FFD-DoE) emphasized the independent variables of the HLB value, co-solvent, and CCT oil contents affecting the optimal compositions for micro- or nanoemulsion formation. The low-energy spontaneous emulsification of the optimized combination at a low Smix content (10%) yielded the translucent oil-in-water Tripeptide-3 nanoemulsions with an internal droplet size of 25.7 ± 1.20 nm, a narrow polydispersity index of 0.237 ± 0.129, and 70.6 ± 0.58% transmittance. The in vitro skin permeation study revealed a significantly higher skin penetration and retention of the Tripeptide-3 nanoemulsions compared to the high surfactant microemulsions and coarse emulsions. Skin irritation and oil control efficacy were evaluated in healthy volunteers before and after product application for 28 days. The obtained nanoemulsions not only decreased sebum production but also enhanced skin moisture levels. In conclusion, the meticulously designed nanoemulsions, incorporating suitable excipients, show a promising delivery system for hydrophilic peptides to control sebum overproduction in oily facial skin.

Isotretinoin self-nano-emulsifying drug delivery system: Preparation, optimization and antibacterial evaluation

PurposeIsotretinoin (ITN) is a poorly water-soluble drug. The objective of this study was to design a successful liquid self-nanoemulsifying drug delivery system (L-SNEDDS) for ITN to improve its solubility, dissolution rate, and antibacterial activity. MethodsAccording to solubility and emulsification studies, castor oil, Cremophor EL, and Transcutol HP were selected as system excipients. A pseudo ternary phase diagram was constructed to reveal the self-emulsification area. The developed SNEDDS were visually assessed, and the droplet size was measured. In vitro release studies and stability studies were conducted. The antimicrobial effectiveness against multiple bacterial strains, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and different accessory gene regulator (Agr) variants were investigated for the optimum ITN-loaded SNEDDS formulation. ResultsCharacterization studies showed emulsion homogeneity and stability (%T 95.40–99.20, A graded) with low droplet sizes (31.87 ± 1.23 nm–115.47 ± 0.36 nm). It was found that the developed ITN-SNEDDS provided significantly a higher release rate (>96 % in 1 h) as compared to the raw drug (<10 % in 1 h). The in vitro antimicrobial activities of pure ITN and ITN-loaded SNEDDS demonstrated a remarkable inhibitory effect on bacterial growth with statistically significant findings (p < 0.0001) for all tested strains when treated with ITN-SNEDDS as compared to the raw drug. ConclusionThese outcomes suggested that SNEDDS could be a potential approach for improving solubility, dissolution rates, and antibacterial activity of ITN.

Development and Ex-Vivo Skin Permeation of Sildenafil Citrate Microemulsion System for Transdermal Delivery

Background: This study aimed to develop a microemulsion (ME)-based skin delivery platform containing sildenafil citrate (SC)-ME and evaluate its in vitro skin permeability. Methods: Accurate MEs were prepared using pseudo-ternary phase diagrams and a full factorial design with three variables at two levels. After the design phase, suitable ratios of oil, water, and a mixture of surfactant (S) and cosurfactant (CS) were selected to prepare various SC-ME formulations. These SC-MEs were analyzed for stability, droplet size, in vitro SC release, skin permeability, and viscosity properties. Results: The droplet size of the ME samples ranged from 6.24 to 32.65 nm, with viscosities between 114 to 239 cps. Release profiles indicated that 26 to 60% of SC was released from the different SC-MEs within 24 hours. All ME formulations significantly enhanced the permeability coefficient (P) through rat skin. Specifically, the flux (Jss) in SC-ME7 increased by approximately 117 times (Jss = 0.0235 mg/cm2.h) compared to the control sample (0.0002 mg/cm2.h). Conclusions: The study concluded that the proportions of the water or oil phase and the S/CS mixture in the MEs significantly influenced the physicochemical characteristics and permeation parameters. The selected MEs improved both the permeability coefficient and the rate of permeation through rat skin. The enhanced drug delivery through and into deep skin layers is a key attribute of an ideal dermal ME. These findings suggest that MEs could serve as effective transdermal delivery systems for SC and similar drugs. However, in vivo assays and clinical research are needed to confirm the therapeutic efficacy of MEs.

LIQUID AND SOLID SELF-EMULSIFYING DRUG DELIVERY SYSTEMS (SEDDS) CONTAINING VALSARTAN: STABILITY ASSESSMENT AND PERMEABILITY STUDIES

Objective: Valsartan (VST) is a Biopharmaceutical classification system (BSC) class II active ingredient with a bioavailability of approximately 25% and is utilized to treat high blood pressure (hypertension). This study aimed was to showcase the stability and increase the permeability of VST by developing self-emulsifying drug delivery systems (SEDDS) and solidified SEDDS (S-SEDDS) formulations. Material and Method: The ratios of the components were determined by the pseudo-ternary phase diagram, and the characterization studies were conducted in the previous study. Stability was performed in long-term (25±2˚C, 60±5% relative humidity) and accelerated (40±2˚C, 75±5% relative humidity) conditions. The intestinal permeability of SEDDS formulations was evaluated by Caco-2 cells. Result and Discussion: Formulations for 12 month, droplet sizes were found to be 67.52 ± 5.26 nm and 176.93 ± 17.34 nm for SEDDS of VST (VST-SEDDS) and S-SEDDS of VST (VST-S-SEDDS), respectively. During this period, polydispersity indexes were: VST-SEDDS, 0.56±0.1; VST-S-SEDDS, 0.58±0.05. Both formulations increased VST permeability across Caco-2 cells: VST-SEDDS by 2.32x (powder) and 2.18x (commercial); VST-S-SEDDS by 1.38x (powder) and 1.30x (commercial). The formulation components did not have cytotoxic effects. These results demonstrated that newly developed VST-SEDDS and VST-S-SEDDS formulations with high permeability may be a desirable approach for antihypertensive therapy.

Preparation of Compound Salvia miltiorrhiza-Blumea balsamifera Nanoemulsion Gel and Its Effect on Hypertrophic Scars in the Rabbit Ear Model.

Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza-Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo. After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-β1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.

African Breadfruit Seed Oil as Lipid Phase of Self-Emulsifying Drug Delivery System for Improved Gastrointestinal Fluid Solubility of Ibuprofen: Design and Evaluation

Introduction: Rain forest vegetations all over the world produce large quantity of economically important seed oils which, in most developing countries are utilized only as food condiments but hardly employed in pharmaceutical formulations.&#x0D; Objectives: The purpose of this work was to formulate ibuprofen-loaded self-emulsifying drug delivery system for the enhancement of the gastrointestinal fluid solubility of this poorly water soluble drug.&#x0D; Methods: The breadfruit seed oil was extracted by the soxhlet extraction technique and characterized for various physicochemical properties including acid, iodine, peroxide, saponification values and organoleptic properties. The super saturation solubility process, water titration studies and pseudo ternary phase diagrams were used to select and quantify the components of the emulsion systems. The liquid self-emulsifying drug delivery systems were converted to solid forms by adsorption onto a blend of miceocrystalline cellulose and Aerosil-200 powders. The resulting wet mass was dried and processed for encapsulation.&#x0D; Results: The percentage yield of the oil from the extraction process was 20.68 % while the acid, iodine, and saponification values were, 4.12 ± 1.24, 21.91 ± 0.88, and 302.45 ± 1.22 respectively. The ibuprofen exhibited higher solubility in the hydrolysed oil than in the crude form. Fourier transform infrared analysis did not reveal existence of component incompatibility. The optimized liquid and solid emulsions exhibited standard characteristics that were compatible to previous literature reports. The formulations also exhibited superior drug release properties over two control samples.&#x0D; Conclusion: It was concluded that Breadfruit seed oil has the potential to function as the lipid component of ibuprofen-loaded self-emulsifying drug delivery system formulated to enhance the aqueous solubility of the drug.

Enhancing collagen based nanoemulgel for effective topical delivery of Aceclofenac and Citronellol oil: Formulation, optimization, in-vitro evaluation, and in-vivo osteoarthritis study with a focus on HMGB-1/RAGE/NF-κB pathway, Klotho, and miR-499a.

The majority of conventional osteoarthritis (OA) treatments are based on molecular adjustment of certain signaling pathways associated with osteoarthritis (OA) pathogenesis, however there is a significant need to search for more effective and safe treatments. This study centers around formulating Aceclofenac (ACF) with high bioavailability in combination with Citronellol oil and collagen. The optimal concentrations of Citronellol oil/D-Limonene oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were studied for thermophysical stability. Thermodynamically stable formula were analyzed for droplet size, zeta potential, and in-vitro permeation. Then, collagen based nanoemulsion were prepared to capitalize on its efficacy in reducing osteoarthritis side effects and characterized for nano size properties. Formulae F10 and F10C were chosen as optimum nanosize formula. Hense, they were prepared and characterized as nanoemulgel dosage form. The nanoemulgel formulae F10NEG1 and F10CNEG1 showed reasonable viscosity and spreadability, with complete drug release after 4h. These formulae were chosen for further In vivo anti-OA study. Collagen based ACF/citronellol emugel were able to modulate HMGB-1/RAGE/NF-κB pathway, mitigating the production of inflammatory cytokine TNF-α. They were also able to modulate Klotho and miR-499, reducing serum CTXII and COMP, by reducing the cartilage destruction. Histological investigations validated the efficacy, safety, and superiority of Aceclofenac in combination with Citronellol oil and collagen (F10CNEG1) over solo the treated group (F10NEG1 and blank). Hence, the findings of the current work encourage the use of this promising combined formula in treatment of OA patients.

Improving cellular uptake and synergetic anti-tumor effects of magnolol and Brucea javanica oil through self-microemulsion

Objective Magnolol (MG) and Brucea javanica (L.) Merr. oil (BJO) possess synergetic anti-tumor effects, but have poor water solubility and stability, which results in low oral bioavailability. Significance The MG loaded self-microemulsion drug delivery system (MG-SMDDS) with BJO as oil phase component was utilized to improve the cellular uptake and synergetic anti-tumor effects. Methods Compatibility study and pseudoternary phase diagram (PTPD) were respectively employed to screen for the composition and proportion of oil phase in the formulation. Central composite design-effect surface method was applied to optimize proportion of each formulation condition. The droplet size, ζ-potential, colloid stability, encapsulation rate (ER) and in vitro dissolution rate of MG-SMDDS were evaluated. Furthermore, cellular uptake and cytotoxicity of the microemulsion on HepG2 cells were assessed. Results The optimal composition of MG-SMDDS was: MG (9.09%), castor oil (7.40%), BJO (2.47%), Cremophor EL 35 (54.04%) and 1, 2-propanediol (27.01%). The MG-SMDDS exhibited satisfactory droplet size, ζ-potential, colloid stability and ER, as well as faster dissolution rate than free MG. More importantly, SMEDDS containing BJO could enhance the cellular uptake and cytotoxicity of free BJO and free MG on tumor cells. Conclusions The BJO self-microemulsion delivery technique can provide an idea for design of oral delivery vehicles based on BJO.

Enhancing oral bioavailability of an antifungal thiazolylhydrazone derivative: Development and characterization of a self-emulsifying drug delivery system

RN104 (2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole) is a thiazolylhydrazone derivative with prominent antifungal activity. This work aimed to develop a self-emulsifying drug delivery system (SEDDS) loaded with RN104 to improve its biopharmaceutical properties and enhance its oral bioavailability. Medium chain triglycerides, sorbitan monooleate, and polysorbate 80 were selected as components for the SEDDS formulation based on solubility determination and a pseudo-ternary phase diagram. The formulation was optimized using the central composite design in response surface methodology. The optimized condition consisted of medium chain triglycerides, sorbitan monooleate, and polysorbate 80 in a mass ratio of 65.5:23.0:11.5, achieving maximum drug loading (10 mg/mL) and minimum particle size (118.4 ± 0.7 nm). The developed RN104-SEDDS was fully characterized using dynamic light scattering, in vitro release studies, stability assessments, polarized light microscopy, and transmission electron microscopy. In vivo pharmacokinetic studies in mice demonstrated that RN104-SEDDS significantly improved oral bioavailability compared to free RN104 (the relative bioavailability was 2133 %). These results clearly indicated the successful application of SEDDS to improve the pharmacokinetic profile and to enhance the oral bioavailability of RN104, substantiating its potential as a promising antifungal drug candidate.

Study on phase behavior of [C16mim] [br]/CAHS/n-butanol/n-hexane/water microemulsions: synergistic effect of ionic liquid-zwitterionic surfactants

The synergistic effect of ionic liquids (ILs) and anionic surfactants, ILs and cationic surfactants, and ILs and nonionic surfactants to form microemulsions has been studied by other researchers, while the synergistic effect of ionic liquids and zwitterionic surfactants to form microemulsions has not been reported. Here, we report the synergistic effect of imidazolium ionic liquid, 1-hexadecyl-3-methylimidazolium bromide [C16mim] [Br], and betaine-type zwitterionic surfactant, cocamidopropyl hydroxysultaine (CAHS), as surfactants, to form microemulsions with n-butanol, n-hexane and water. Phase behavior of the systems with different mass ratios of two surfactants, varied mass ratios of surfactant to cosurfactant (Km), and different temperatures are investigated by pseudo-ternary phase diagrams. The single-phase region of the microemulsion is maximized when the ratio of CAHS to [C16mim] [Br] is 1:4 and Km is 1.5, with little temperature dependence. The size and the polarity of microemulsions are explored. The synergistic effect of [C16mim] [Br] and CAHS is confirmed by surface tension and interface tension. A universal preparation method to form microemulsions by combining ionic liquids with zwitterionic betaine-type surfactants is provided and it play a pivotal role in broadening the potential uses of ILs in microemulsions.

Microemulsion containing guava leaves essential oil: Enhanced anti-inflammatory, anti-oxidation, anti-tyrosinase activities and skin permeation

In this study, a microemulsion system containing guava leaf essential oil (GLE) was developed to enhance water miscibility, stability and bioactivity. The major chemical components of GLE, d-limonene, and β-caryophyllene, were identified by GC-MS analysis. The microemulsion system consisted of Tween 80 and propylene glycol as the surfactant (S) and co-surfactant (Co–S), respectively, with GLE serving as the oil phase. Three pseudo-ternary phase diagrams were constructed with different S:Co–S ratios (Km) at 2:1, 1:1, and 1:2 to illustrate the microemulsion area. Characterization of GLE contained microemulsions (GLEMEs) was performed using dynamic light scattering (DLS), viscometry, and conductivity measurements. The particle sizes of GLEMEs ranged from 10 to 150 nm. Selected GLEMEs exhibited stable particle sizes for more than 90 days and remained stable over a wide pH range. Additionally, compared to free GLE, these microemulsions demonstrated enhanced anti-tyrosinase and antioxidant activity, as well as improved anti-inflammatory properties. Moreover, microemulsions with high oil content exhibited deeper skin penetration compared to free GLE, while those with high water content accumulated in the upper skin layer.

Phase Equilibrium Studies of Nonferrous Smelting Slags: A Review

Pyrometallurgy is the primary technique for the production of many nonferrous metals such as copper, lead, and zinc. The phase equilibrium information of smelting slags plays an important role in the efficient extraction of metals and energy consumption. The experimental technologies used in phase equilibrium studies are compared. The presentation and applications of the pseudo-ternary and pseudo-binary phase diagrams are demonstrated in the Fe–Si–Ca–Zn–Mg–Al–Cu–S–O system. Experimental results are also compared with the predictions of FactSage to evaluate the accuracy of the current thermodynamic database. This review paper provides comprehensive information for the operation of nonferrous metals and optimization of the thermodynamic database.