Microemulsion Formulation Research Articles

Development and Evaluation of Microemulsion Formualatons of Valsartan for Solubility Enhancement

Microemulsions have attracted considerable amount of interest as potential drug delivery vehicles largely due to their simple method of preparation, stability and their abilities to incorporate a wide range of drugs of varying solubility. O/W microemulsion is expected to increase the solubility by dissolving low water solubility compounds into its dispersed phase and to enhance the oral bioavailability by protecting the drug increasing the rate of absorption and wettability due to surfactants induced permeability changes and smaller droplet size (< 100 nm) and most importantly able to target lymphatic system. 
 In the present study, the drug delivery system contains Valsartan, a hydrophilic component, a lipophillic component, surfactants and co-surfactants. The objective is to provide an increased release of valsartan and increased bioavailability of valsartan. Prepared microemulsion formulations by phase-titration method were evaluated for viscosity, drug content, thermodynamic stability studies and in-vitro dissolution. Resultant microemulsion optimized formulation (ME5) shows drug release (88.2±0.16%.%). Hence, micro-emulsion of valsartan was successfully developed and evaluated.
 Keywords: Microemulsion, Valsartan, solubility, evaluation.

Field demonstration of in-situ microemulsion flushing for enhanced remediation of multiple chlorinated solvents contaminated aquifer

The remediation of in-situ microemulsion flushing for multiple chlorinated solvents contaminated groundwater is challenging, because different chlorinated solvent has major influence on microemulsion formation and solubilization behaviors. This work was conducted to evaluate the remediation effectiveness for various chlorinated solvents contaminated site and monitor the disturbance of groundwater during in-situ microemulsion flushing process. Groundwater at this site was contaminated with chlorobenzene (MCB), chloroaniline and nitrochlorobenzene. The medium layer was mainly composed of fine and silty sand, with average hydraulic conductivity of 4.97 m/d. Results of this field-scale test indicated in-situ microemulsion flushing successfully enhanced the apparent solubility of various chlorinated solvents. Post-flushing concentration of various chlorinated solvents were 1.33–71.6-fold the concentration of pre-flushing values at 10 sampling locations within the test zone. This field was flushed with 16.8 m3 microemulsion, removing approximately 18.49 kg chlorinated solvents. Besides, a trend in the desorption order of various chlorinated solvents was observed. The least hydrophobic pollutant was flushed first, followed by contaminants of increasing hydrophobicity. In addition, during remediation process, the indexes of groundwater fluctuated insignificantly, indicating the reagent had little disturbance to aquifer. This field work demonstrated the feasibility of in-situ microemulsion enhanced remediation via increasing apparent solubility of multiple chlorinated solvents.

Preparation and Characterization of Prednisolone Acetate Microemulsion for Ophthalmic Use

Background: Prednisolone acetate is an ester form of prednisolone. It is used topically as an ophthalmic suspension to treat many inflammatory ocular conditions, where its absorption from suspension is highly variable and has poor dose accuracy. Objectives: The main objective of this research is to formulate and evaluate prednisolone acetate microemulsion for ophthalmic use to increase solubility, residence time, and corneal permeability of the drug to enhance patient compliance and treatment efficacy. Methods: Twenty-four prednisolone acetate-loaded microemulsion (0.5%w/w) formulas were prepared using oleic acid, isopropyl myristate as (oil phase) (1:1), tween 80, labrasol, and cremophor EL as (surfactant), ethanol, polyethylene glycol 400, propylene glycol, transcutol P as co-surfactant and Sörensen isotonic phosphate buffer saline pH 7.4 as the aqueous phase at different Smix ratios (1:1), (1:2) and (2:1) by aqueous titration method to construct pseudoternary phase diagram to determine the existence of microemulsion region. All the prepared formulas were subjected to different evaluation tests to determine the optimum formula. Results: observations of the microemulsion showed that it had a clear and transparent yellowish color, formulation F9 composed of oleic acid and isopropyl myristate in a ratio (1:1) as oil, twee80 as a surfactant, and propylene glycol: ethanol (1:1) in a ratio (2:1) as cosurfactant gave the best particle size (10.18nm), polydispersity index (0.2216), zeta potential (-25,91), % of transmittance (99.382%±0. 09), and drug content (100±0.16). Microemulsion formulation provided considerably higher permeability than the marketed eye drop suspension (Optipred®) and improved bioavailability. Conclusions: The microemulsion-containing prednisolone acetate is a promising ocular carrier for the controlled release of prednisolone acetate in treating anterior segment inflammation. Received: Dec. 2022 Accepted March 2023 Published: Oct.2023

Mini review: recent advances in biosurfactant-based association colloids–formation of microemulsions

In the context of a more sustainable economy, bio-surfactants become increasingly important, due to their independence of petrol-based chemistry, their usually mild synthesis conditions, and in certain cases their pharmacological activity. We have recently discussed self-assembly studies in binary systems of bio-surfactants of microbial origin, or saponins extracted from plants (Hellweg et al., Frontiers in Soft Matter, 2023, 2). In the present review, we focus on the formation of microemulsions based on these molecules. We review the formation and structure of microemulsion systems formed by oil, water, and biosurfactants, with a particular focus on Quillaja saponins and rhamnolipids.

OPTIMIZATION AND CHARACTERIZATION OF ESSENTIAL OILS FORMULATION FOR ENHANCED STABILITY AND DRUG DELIVERY SYSTEM OF MEFLOQUINE

Objective: This work aims to choose suitable essential oil formulations to improve the bioavailability and long-term aqueous stability of mefloquine in drug delivery systems. Methods: Oil phases of pomegranate oil, black cumin seed oil, and garlic oil. To choose the proper oil and surfactant for creating pseudo-ternary phase diagrams, cremophore EL, tween®20 and tween®80 (surfactants), and brij 35 (co-surfactants) were used in a variety of concentrations and combinations (Smix). Mefloquine was estimated to be soluble in a variety of oils, surfactants, and co-surfactants. Drug solubility, drug release research, thermodynamic stability, mean hydrodynamic size and zeta potential. Results: Garlic with smix of cremophore EL and brij 35, Pomegranate with Tween 2.0, and Black cumin seed oil with Tween 80 showed the highest solubilization and emulsification capabilities and were further investigated using ternary phase diagrams. When combined with the co-surfactants under investigation, cremophore EL demonstrated a greater self-emulsification zone than tween® 80 and tween 20. Garlic oil, cremophore EL, and brij 35 nanoemulsion showed smaller size, greater zeta potential, less emulsification time, high transmittance, and better drug solubility than microemulsion formulations on especially those made with tween®20 and tween 80. Mefloquine loaded garlic oil nanoemulsion showed considerably low release in body fluid (32.48%) and a good release in intestinal fluid (82.78%) by 12 h in a drug release study. Conclusion: Garlic oil as the oil phase and a mixture of cremophore EL and brij 35 as the surfactant phase are ideal surfactants and co-surfactant for mefloquine loaded garlic oil nanoemulsion with greater drug release in release kinetics investigation.

Formulation and characterization of micro-emulsions of peppermint and coriander oils extracted by using a supercritical fluid system

ABSTRACT The present study was designed to formulate and characterize the micro-emulsions of peppermint and coriander oil that extracted by using supercritical fluid extraction system. Moreover, Guar gum and maltodextrin were used as coating materials while preparing encapsulates of peppermint and coriander through freeze-drying. The moisture contents of mint leaves and coriander were 81.28 ± 7.12 and 84.62 ± 6.46% respectively whereas the recorded protein content in mint and coriander leaves were 1.456 ± 0.13 and 5.06 ± 0.03% respectively. The crude fat was high in mint leaves as compared to coriander. However, the ash content was 2.98 ± 0.278 in mint and 2.8 ± 0.12 in coriander leaves. The total phenolic contents (TPC) and antioxidant activity coriander essential oil was high as compared to peppermint oil. The results showed the better antioxidant activity of coriander than peppermint. Encapsulation efficiency of powder showed significant results of wall material. T3 (maltodextrin and coriander oil) exhibited better binding capability of bioactive components as compared to guar gum and mint. T3 was coriander and maltodextrin better ability to inhibit the oxidation process and had good DPPH assays as compared to other treatments. This study showed that the T3 (maltodextrin and coriander oil) exhibited better binding capability of bioactive components as compared to guar gum and mint. T3 was (coriander and maltodextrin) better ability to inhibit the oxidation process and had good DPPH assays to other treatments.

Sustained delivery of triamcinolone acetonide from a thermosensitive microemulsion gel system for the treatment of sensorineural hearing loss

Intratympanic administration for the delivery of steroids has been extensively studied but limited because of low permeability of the drug through the row window membrane. Here, to effectively deliver poorly soluble triamcinolone acetonide (TA), microemulsions (ME) were prepared from Capmul MCM (oil), Cremophor RH40 (surfactant), and tetraglycol (cosurfactant) based on solubility studies, emulsifying ability test, and pseudoternary phase diagrams. Microemulsion gel (MEG) was prepared by mixing TA-ME with a poloxamer hydrogel base. The physicochemical properties of ME and MEG formulations were characterized, and the toxicity and oto-protective effectiveness were evaluated in vitro and in vivo. The ME-3 formulation showed a small droplet size (16.5 ± 0.2 nm), narrow PDI (0.067 ± 0.041), and enhanced TA solubility (2619.7 ± 57.6 μg/g). The optimized MEG demonstrated temperature-dependent gelation with a gelation time of 208 ± 10 sec at 37 °C. Slow degradation of the gel matrix sustained release of TA from MEG compared to the ME formulation. Both TA-ME and TA-MEG were found to be nontoxic to NIH3T3 cells at the test concentrations (0 to 5 µg/mL), and biocompatible after intratympanic administration to mice. The incorporation of ME into thermosensitive hydrogels prolonged retention of TA at the site of administration until 6 days. As a consequence, the enhanced drug absorption into the cochlea in TA-MEG group (approximately 2 times higher than other groups) protected hair cells, spiral ganglion neurons, and stria vascular cells from cisplatin-induced damage. Therefore, this injectable TA-loaded MEG is an effective and safe vehicle for the sustained delivery of triamcinolone acetonide into the inner ear.

Tea tree (Melaleuca alternifolia) Essential Oil Concentration in Microemulsion with Antibacterial and Antifungal Activity: An Overview

Abstract: The tea tree (Melaleuca alternifolia), a member of the Myrtaceae family, is a valuable medicinal and aromatic plant. Tea Tree essential oil (TTO) has many medical applications, including antibacterial, antifungal, antiviral, antiprotozoal, anti-inflammatory, antioxidant, and anticancer properties. Although the concentration of TTO in a microemulsion is of economic interest, very few studies on this product have been conducted. In this study, we look at how different tea tree oil concentrations in microemulsion formulations affect susceptibility to various bacteria and fungi. TTO susceptibility in a diverse range of microbial species has now been studied using data from a previously published literature review survey. Most bacteria are resistant to TTO at concentrations as low as 1.0 percent, but mucosal skin staphylococci and micrococci, Enterococcus faecalis, and Pseudomonas aeruginosa have minimum inhibitory concentrations much higher than 2 percent. TTO susceptibility in fungi has only recently been scrutinized. Fungicidal dosages range from 0.12 to 2 percent, with minimum inhibitory concentrations ranging from 0.03 to 0.5 percent and the only notable exception is Aspergillus niger, which contains fungicidal concentrations of up to 8%. The review emphasizes the importance of new antibacterial and antifungal formulations, as well as the role of natural essential oils in the discovery of new antibacterial and antifungal agents, and discusses, in brief, all constituents derived from the essential oil (tea tree) that are in preclinical and clinical development. This paper summarizes human and food-borne bacteria and fungi susceptibility to tea tree essential oils and their constituents. Among the many tested, essential oils of spices and herbs (Melaleuca alternifolia) were found to have the strongest antimicrobial properties. This review looks at a wide range of scientific literature, including Sci-hub, Google Scholar, Pub, Chem, NCBI, and web books.

Design and evaluation of adapalene microemulsion for transfollicular drug delivery through guinea pig skin.

Acne vulgaris can be treated topically with adapalene, a synthetic derivative of naphthoic acid with retinoid activity. Adapalene has a very low rate of percutaneous absorption and is almost completely insoluble in water. To obviate this problem, microemulsion (ME) carrier is used. The study's goals were to create and characterize adapalene-loaded ME and assess the drug's transfollicular route of penetration to see if hair follicles can serve as a conduit for the drug to enter the skin. Adapalene microemulsions (MEs) are made by combining the right amounts of the cosurfactant (propylene glycol), surfactant (Tween 80 and Span 20), and oil phase (oleic acid-Transcutol P (10:1)). Physical and chemical characteristics of MEs, including droplet size, stability, viscosity, drug release, and in vitro skin permeability via guinea pigs' hairy and non-hairy skin, were assessed. The range of 13.86-56.16 nm was found to be the average droplet size of ME formulations. The range of viscosities was 117-240 cps. The drug release profile reveals that 95.374 percent of the drug was released within the experiment's first 24 h. Compared to the adapalene control (aqueous suspension), all MEs enhanced the adapalene flow through both hairy and non-hairy skin. The surfactant/cosurfactant ratio had an impact on the amount of drug that passed through both skins because a larger ratio enhanced the adapalene affinity in the follicular route. Furthermore, the proportions of the water and oil phases in formulations, as well as the S/C ratio, have a significant impact on the physicochemical characteristics and adapalene permeability across both pathways.

DEVELOPMENT AND EVALUATION OF MICROEMULSION FORMULATIONS OF BIFONAZOLE

Aim and objective: The purpose of this study was to develop microemulsion formulations for topical delivery of bifonazole with an objective to increase the solubility of the drug. Methods: Total 5 microemulsion formulations were developed using water titration method. Capmul Pg-12 (oil), Tween-80: (surfactant) and Propylene glycol (co-surfactant) were used in different ratio based on the solubility and emulsification efficiency. Prepared formulations were evaluated on different parameters like transmittance (%), pH, refractive index, viscosity, drug content, solubility, and in-vitro release study Franz diffusion cell. Ternary phase diagram was prepared using oil (Capmul Pg-12), surfactant (Tween 80), co-surfactant (Propylene glycol) in different ratio Results: The % transmission was found to be in the range of 98.47±0.09 to 99.2±0.08%, the pH value was found to be in the range of 3.34±0.08 to 4.02±0.09, refractive index in the range of 1.3418±0.016 to 1.3818±0.004, drug content was found to be in the range of 98.47± 0.08 to 99.62±0.02 %, viscosity was found to be in the range of 65.23±2.1 to 71.56±5.77%. It was seen that after 4 hours of diffusion, the drug released from the formulation ME5 faster and more than that of the other ratios i.e., 91.2±0.06%. It was observed that drug release was governed by the diffusion process. Conclusion: On the basis of different evaluation parameters microemulsion formulations of batch ME5 were found to be the best. Present study concludes successful delivery of Bifonazole by the means of microemulsion formulations Peer Review History: Received: 4 March 2023; Revised: 26 April; Accepted: 20 June 2023, Available online: 15 July 2023 Academic Editor: Dr. Marwa A. A. Fayed, University of Sadat City, Egypt, maafayed@gmail.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Rola Jadallah, Arab American University, Palestine, rola@aauj.edu Dr. Taiwo O Elufioye, University of Ibadan, Nigeria, toonitaiwo@yahoo.com

A Study of Microemulsion Systems for Transdermal Delivery of Risperidone Using Penetration Enhancers

The aim of this study was to develop and characterize microemulsion formulations using penetration enhancers as potential transdermal delivery systems for risperidone. Initially, a simple formulation of risperidone in Propylene Glycol (PG) was prepared as a control formulation, together with formulations incorporating various penetration enhancers, alone and/or in combination, and also microemulsion formulations with various chemical penetration enhancers, were prepared and all were evaluated for risperidone transdermal delivery. An ex-vivo permeation study was carried out using human cadaver skin and vertical glass Franz diffusion cells to compare all the microemulsion formulations. The microemulsion prepared from oleic acid as the oil (15%), Tween 80 (15%) as the surfactant and isopropyl alcohol (20%) as the co-surfactant, and water (50%) showed higher permeation with a flux value of 32.50±3.60 ug/hr/sq.cm, a globule size of 2.96±0.01 nm, a polydispersity index of 0.33±0.02 and pH of 4.95. This novel in vitro research disclosed that an optimized microemulsion formulated using penetration enhancers was able to increase permeation of risperidone by 14-fold compared to the control formulation. The data suggested that microemulsions may be useful in the delivery of risperidone via the transdermal route.

An experimental workflow to assess the applicability of microemulsions for conformance improvement in oil-bearing reservoir

A comprehensive workflow approach is necessary to link multiple experimental tasks and identify microemulsion (ME) formulations with ‘optimal’ stability, displacement behavior and technical feasibility in the petroleum industry. In this paper, a systematic approach is described with the aid of a case study which involves the formulation of an anionic sodium dodecyl sulfate-based microemulsion. The design of such ME systems requires a proper methodology, substantial laboratory work, and functional assessment from research/industrial viewpoints. The surfactant has been screened in terms of its micellization potential, followed by phase behavior analysis and Winsor classification of prepared microemulsions. The desired composition(s) are characterized via several tools to determine droplet size, morphology, oil/water solubilization potentials and salinity scan results. The suitability of the microemulsion system for conformance improvement technology (CIT) is proposed to be assessed via physicochemical evaluation studies encompassing two attributes: rheology and stability. For a favorable ‘conforming’ drive, the microemulsion must exhibit phase stability, sufficient injectivity, and moderate-to-high viscosity under shear. Technical assessment by the industry and research team must also include factors related to cost, availability of chemicals, environmental degradation, and reservoir considerations. The article demonstrates a comprehensive all-inclusive workflow methodology to design and formulate surfactant-stabilized microemulsions via case study analysis for application in CIT. This represents a sound approach to identifying efficient, cost-effective injection fluid systems and provides a framework to identify useful parameters for ME formulation design and employ the proposed (effective) strategy for conformance control.

The Enhanced Skin Permeation of Flavonoids Via the Application of a Coamorphous in a Microemulsion Formulation

Improving the permeability and solubility of poorly water-soluble compounds is a major difficulty in skin permeation. In this study, we investigated whether using a pharmaceutical technique such as applying coamorphous to a microemulsion enhances the skin permeation of polyphenolic compounds. The melt-quenching technique created the coamorphous system between naringenin (NRG) and hesperetin (HPT), two polyphenolic compounds with poor water solubility. By creating a supersaturated state, the aqueous solution of coamorphous NRG/HPT demonstrated improved NRG and HPT skin permeation. However, as both compounds precipitated, the supersaturation ratio decreased. In contrast to crystal compounds, incorporating coamorphous material into microemulsions enabled the preparation of microemulsions in a wider formulation range. Additionally, compared to microemulsions with crystal compounds and an aqueous suspension of coamorphous, microemulsions with coamorphous NRG/HPT increased skin permeation of both compounds by more than four times. These results suggested that interactions between NRG and HPT are maintained in the microemulsion and enhance both compounds' skin permeation. An approach for improving the skin permeation of poorly water-soluble chemicals would be to apply a coamorphous system to a microemulsion.

Highly-Controlled Soft-Templating Synthesis of Hollow ZIF-8 Nanospheres for Selective CO2 Separation and Storage.

Global warming is an ever-rising environmental concern, and carbon dioxide (CO2) is among its major causes. Different technologies, including adsorption, cryogenic separation, and sequestration, have been developed for CO2 separation and storage/utilization. Among these, carbon capture using nano-adsorbents has the advantages of excellent CO2 separation and storage performance as well as superior heat- and mass-transfer characteristics due to their large surface area and pore volume. In this work, an environmentally friendly, facile, bottom-up synthesis of ZIF-8 hollow nanospheres (with reduced chemical consumption) was developed for selective CO2 separation and storage. During this soft-templating synthesis, a combined effect of ultra-sonication and low-temperature hydrothermal synthesis showed better control over an oil-in-water microemulsion formation and the subsequent growth of large-surface-area hollow ZIF-8 nanospheres having excellent particle size distribution. Systematic studies on the synthesis parameters were also performed to achieve fine-tuning of the ZIF-8 crystallinity, hollow structures, and sphere size. The optimized hollow ZIF-8 nanosphere sample having uniform size distribution exhibited remarkable CO2 adsorption capability (∼2.24 mmol g-1 at 0 °C and 1.75 bar), a CO2/N2 separation selectivity of 12.15, a good CO2 storage capacity (1.5-1.75 wt %), and an excellent cyclic adsorption/desorption performance (up to four CO2 adsorption/desorption cycles) at 25 °C. In addition, the samples showed exceptional structural stability with only ∼15% of overall weight loss up to 600 °C under a nitrogen environment. Therefore, the hollow ZIF-8 nanospheres as well as their highly controlled soft-templating synthesis method reported in this work are useful in the course of the development of nanomaterials with optimized properties for future CO2 capture technologies.

New trends towards glaucoma treatment: Topical osmoprotective microemulsions loaded with latanoprost

The chronic use of hypotensive agents eventually leads to ocular surface damage and poor patient compliance during glaucoma management. Thus, new sustained drug delivery systems are needed. This work aimed to develop osmoprotective latanoprost-loaded microemulsion formulations as new potential glaucoma treatments with ocular surface protective properties. The microemulsions were characterized and latanoprost encapsulation efficacy determined. In-vitro tolerance, osmoprotective efficacy, cell internalization as well as cell-microemulsion interactions and distribution were performed. In vivo hypotensive activity was conducted in rabbits to assess intraocular pressure reduction and relative ocular bioavailability. Physicochemical characterization showed nanodroplet sizes within 20–30 nm, being in vitro tolerance within 80 and 100% viability in corneal and conjunctival cells. Besides, microemulsions exhibited higher protection under hypertonic conditions than untreated cells. Cell fluorescence lasted for 11 days after short exposure to coumarin-loaded microemulsions (5 min) showing extensive internalization in different cell compartments by electronic microscopy. In vivo studies exhibited that a single instillation of latanoprost-loaded microemulsions reduced the intraocular pressure for several days (4–6 days without polymer and 9–13 days with polymers). Relative ocular bioavailability was 4.5 and 19 times higher than the marketed formulation. These findings suggest the use of these microemulsions as potential combined strategies for extended surface protection and glaucoma treatment.

The formation and temperature stability of microemulsion emulsified by polyoxyethylene ether surfactant

The effect of polyoxyethylene chain length on the formation and temperature stability of W/O microemulsion emulsified by polyoxyethylene ether surfactant is investigated by dissipative particle dynamics simulation (DPD) on the mesoscopic level. The results show that W/O microemulsions can be formed by three polyoxyethylene chain length ether nonionic surfactants with decreasing the water-oil ratio equal to increasing the oil phase content. However, W/O microemulsion is most easily formed by diethylene glycol monododecyl ether (H1T2) with the smallest oxyethylene base.The results of temperature stability show that W/O microemulsion emulsified by H1T2 has better stability resistant to high or low temperature. In addition, the interfacial tension of the W/O microemulsion system is the lowest, the end-to-end distance of the surfactant molecule is smallest, and the molecular chain is the most curved at the water-oil interface. The theoretical simulation results can guide the formation of the W/O microemulsion induced by polyoxyethylene ether nonionic surfactant, and provide the guidance for its practical application.

Development, characterization of naringenin-loaded promising microemulsion formulations, and demonstration of anti-aging efficacy by in vitro enzyme activity and gene expression

Development, characterization of naringenin-loaded promising microemulsion formulations, and demonstration of anti-aging efficacy by in vitro enzyme activity and gene expression

Exploring the Versatility of Microemulsions in Cutaneous Drug Delivery: Opportunities and Challenges.

Microemulsions are novel drug delivery systems that have garnered significant attention in the pharmaceutical research field. These systems possess several desirable characteristics, such as transparency and thermodynamic stability, which make them suitable for delivering both hydrophilic and hydrophobic drugs. In this comprehensive review, we aim to explore different aspects related to the formulation, characterization, and applications of microemulsions, with a particular emphasis on their potential for cutaneous drug delivery. Microemulsions have shown great promise in overcoming bioavailability concerns and enabling sustained drug delivery. Thus, it is crucial to have a thorough understanding of their formulation and characterization in order to optimize their effectiveness and safety. This review will delve into the different types of microemulsions, their composition, and the factors that affect their stability. Furthermore, the potential of microemulsions as drug delivery systems for skin applications will be discussed. Overall, this review will provide valuable insights into the advantages of microemulsions as drug delivery systems and their potential for improving cutaneous drug delivery.

Phase behavior and structure of a biocompatible microemulsion based on Tween 20, 2-ethylhexylglycerine and isopropyl palmitate in water

Microemulsions are thermodynamically stable mixtures of water and oil. For many applications, such as in cosmetics, it is important that the components are biocompatible. For the formulation of a new biocompatible microemulsion based on Tween 20 (Tw20) surfactant, the glycerol ether 2-ethylhexylglycerin (EHG) is employed as an alternative to commonly used short- to medium chain alcohols as cosurfactant. Tw20 itself is not capable of any significant solubilization but the addition of EHG allows to enhance the solubilization capacity for the polar oil isopropyl palmitate (IPP) largely. At a Tw20 to EHG molar ratio of 1:12, i.e., very large excess of cosurfactant, the solubilization capacity is increased by nearly three orders of magnitude compared to a pure Tw20 solution. The resulting oil-in-water (O/W) microemulsion is studied using static and dynamic light scattering (SLS/DLS) and small-angle neutron scattering (SANS). The SANS spectra are analyzed with a core–shell ellipsoid model, which indicates formation of oblate droplets at higher EHG content. Dynamic light scattering experiments confirm the presence of microemulsion droplets with hydrodynamic radii increasing from 3.8 to 19.8 nm upon addition of cosurfactant. In summary, this study shows that EHG is a cosurfactant that enhances the solubilization properties of a biocompatible surfactant largely and thereby renders it very useful for formulations.

Development and cytotoxicity evaluation of multiple nanoemulsions for oral co-delivery of 5-fluorouracil and short chain triglycerides for colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in the world, but current chemotherapy options are limited due to adverse effects and low oral bioavailability of drugs. In this study, we investigated the obtainment parameters and composition of new multiple nanoemulsions (MN) based on microemulsions for oral co-delivery of 5-fluorouracil (5FU) and short-chain triglycerides (SCT, either tributyrin or tripropionin). The area of microemulsion formation was increased from 14% to 38% when monocaprylin was mixed with tricaprylin as oil phase. Addition of SCT reduced this value to 24–26%. Using sodium alginate aqueous dispersion as internal aqueous phase (to avoid phase inversion) did not further affected the area but increased microemulsion viscosity by 1.5-fold. To obtain the MN, selected microemulsions were diluted in an external aqueous phase; droplet size was 500 nm and stability improved using polyoxyethylene oleyl ether at 1–2.5% as surfactant in the external phase and a dilution ratio of 1:1 (v/v). 5FU in vitro release could be better described by the Korsmeyer-Peppas model. No pronounced changes in droplet size were observed when selected MNs were incubated in buffers mimicking gastrointestinal fluids. The 5FU cytotoxicity in monolayer cell lines presenting various mutations was influenced by its incorporation in the nanocarrier, presence of SCT and cell mutation status. The MNs selected reduced the viability of tumor spheroids (employed as 3D tumor models) by 2.2-fold compared to 5FU solution and did not affect the survival of the G. mellonella, suggesting effectiveness and safety.