Water Dilution Line Research Articles

The effect of the structural transition within a direct hexagonal (HI) mesophase on the internal lipid mobility

The current study analyzes the cause of the extreme change in dermal permeation resulting from a minute structural transformation within a temperature-sensitive direct hexagonal mesophase by a multiple-method approach. The evaluated mesophase is composed of Tween 80, propylene glycol, isopropyl myristate, benzyl alcohol, and water. 1 wt% ketoconazole (KCZ) was loaded in the concentrate as a model lipophilic drug. Evaluation of the mesophase at 25 °C indicated that the hexagonal mesophase region (33.0–42.5 wt% water along water dilution line N91) consists of two distinct structures. At water content below 39.0 wt%, the mesophase is structured as a bidiscontinuous hexagonal mesophase (BHM) consisting of occluded hydration centers and hexagonally oriented direct micelles. Above 39.5 wt% water, dilution of the BHM obstructs the hydration centers, transforming the mesophase to a water continuous hexagonal mesophase (CHM). FTIR evaluation indicated that the both the added water upon dilution and the water molecules released from the hydration centers bind to the surfactant's non-hydrated ethoxylates. Evaluation of the structural transition by PGSE-NMR and DSC indicated that the binding of water to the surfactant's heads immobilizes the inner core of the solubilized lipids. The reduction of the lipid core’s mobility prevents its crystallization at cryogenic temperatures. SAXS and rheological evaluations pointed out that both BHM and CHM are temperature-sensitive mesophases, which lose their range order and storage modulus at 32 °C. Obstruction of the hexagonal mesophase enhances KCZ's diffusion from both mesophases’ via cellulose acetate at 35 °C. Despite the similarity of both mesophases at elevated temperatures (35 °C), the lipidic inner core’s rotational correlation time for deformed CHM micelles remains substantially lower than from the deformed BHM. Franz cell evaluation indicated that the lipidic core mobility substantially influences KCZ's distribution upon dermal application, whereas from CHM KCZ's transdermal flux via a dermatome bovine graft at 35 °C, was 1.60 ± 0.28 µg/cm2 h, no flux was detected from BHM. On the other hand, KCZ's dermal accumulation from BHM, at 35 °C, was found to be more than double than that from CHM, indicating that the decrease in the lipidic inner core’s mobility of direct micelles prevents the accumulation of lipophilic compounds in the dermis, thereby enhancing their transdermal flux.

Formation of sacha inchi oil microemulsion systems: effects of non-ionic surfactants, short-chain alcohols, straight-chain esters and essential oils.

This study reports the formation of sacha inchi oil (SIO) microemulsions for food and cosmetic applications. Effects of non-ionic surfactants, short-chain alcohols, essential oil and straight-chain esters on the phase behavior and formulation of U-type microemulsion were investigated. Pseudo ternary phase diagrams were constructed to assess the influence of these factors using water titration method. Structural transitions were measured along several water dilution lines using conductivity and viscosity tools. Among four different surfactants, Tween 80 solubilized the maximum oil and induced the formation of a U-type microemulsion system. Oil solubilization was decreased in the presence of short-chain alcohols. In addition, the system containing straight-chain esters as the cosolvent showed a higher expansion effect in the U-type areas than that containing essential oils. Finally, upon water dilution of three systems with SIO/ethyl acetate of 1:1, 1:2 and 1:3, microstructural transition from W/O to bicontinuous occurred at 200 g kg-1 (w/w) water content, and then to O/W structure at 650 g kg-1 (w/w) water content. Straight-chain esters as cosolvent is a potential strategy to extend the dilutability of SIO microemulsions. © 2021 Society of Chemical Industry.

Phase inversion characteristics observed upon water dilution of a bidiscontinuous phase

This study presents a directly aggregated pseudo-ternary system. The three apexes of the investigated system represent a surfactant phase [Tween 80:propylene glycol (9:1 wt ratio)], an oil phase [isopropyl myristate:benzyl alcohol (7.5:2.5 wt ratio)], and water. Within the pseudo-ternary system, water dilution line, termed N91 (90 wt% surfactant phase and 10 wt% oil phase), was found to represent transparent and thermodynamically stable compositions from concentrate to high water dilution (>95 wt% water). Despite that the system was found to be directly aggregated, dilution line N91 exhibited classical L2→L1 phase inversion characteristics (at 39 wt% water). To explain this phenomenon, a novel structural interpretation regarding the observed inversion as an obstruction of the bidiscontinuous phase, consisting of oil and water-segregated domains, is proposed. The evaluation of dilution line N91 was based on electrical conductivity, SAXS, SD-NMR, rheometry, DSC and cryo-TEM.The structural transitions along water dilution line N91 were found to be as follows: 'pseudo L1' (pseudo direct surfactant-oil aggregates) → bi-discontinuous structure (of which partial is a hexagonal H1 mesophase) → L1.We concluded that the high concentration of low CPP (critical packing parameter) surfactant plays a major role in determining the system's geometry throughout the water dilution line. As a result, the proposed interpretation of the structural inversion observed along dilution line N91 differs from the classical U-type inversion interpretation (L2 →bicontinuous →L1).

Lessons Learned From Electrical Submersible Pumps Installed in High-Salinity and Corrosive Reservoir, TAGI Formation

Summary An experience of electrical-submersible-pump (ESP) -issues troubleshooting to overcome the high-corrosion media of GSA wells is presented. Additionally, actions taken to extend the run life of pumps are explained. GSA is the company in Algeria that adopted the ESP system including all services; therefore, there was no chance to share experience with other entities in the country. Thus, it became necessary to try all available approaches during a period of 10 years to mitigate ESP failures and, eventually, production downtime. To overcome the high salinity of >320 g/L, several actions were introduced by either of two ways—ESP equipment or well completion. Simple motors and protectors were changed to tandem to prevent water penetration inside the motor. Power cable was changed from galvanized to Monel armor for high resistance to corrosion. For well completion, single or double ½-in. water-dilution lines were adopted and were run along tubing and connected to tail pipe, which runs to perforations. Modification in completion metallurgy also took place, when carbon steel was replaced by Super 13Cr. Supplementary actions were taken at the surface; the pressure switch was connected with a variable-speed drive (VSD) to smoothly shut down the ESP for unforeseen surface-controlled subsurface-safety-valve (SCSSV) closures. The adopted actions yielded considerable positive results. ESP failures that originated from the motor were reduced from four per year during 2012 to only one failure in 2016. However, salt-deposition blocs were almost prevented, and resulted in decrement in bullheading and coiled-tubing interventions by 85%, except for some wells when salt-bloc buildup was occasionally quicker and more important than water-dilution rate. Running a ½-in. injection line along with the tail pipe lowered ESP-shutdown frequency. Also, changing the power-cable type gave roughly good results. After running Monel armor, the number of related power-cable failures decreased, contributing to the reduction of whole failures, because related power-cable failure represented 70% of ESP failures in 2015. Considering Super 13Cr instead of carbon-steel tubing gave positive indications, and reduced sharply related tubing-integrity failure. The problem still exists, however, with very low frequency. For surface equipment, all unforeseen SCSSV closures actuated from the control panel are always accompanied by a gradual decrement of frequency and, consequently, smoother ESP shutdown. Because our organization is the company that uses ESP with a proper sense in Algeria, this paper presents some best practices to be considered for other companies and ESP contractors that are based in the country or abroad that intend to install an ESP system in very high-salinity and corrosive fields and to adopt a lease model for downhole equipment.

Gel-like TPGS-Based Microemulsions for Imiquimod Dermal Delivery: Role of Mesostructure on the Uptake and Distribution into the Skin.

The aim of this work was to develop an innovative microemulsion with gel-like properties for the cutaneous delivery of imiquimod, an immunostimulant drug employed for the treatment of cutaneous infections and neoplastic conditions. A pseudoternary phase diagram was built using a 1/1 TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate)/Transcutol mixture as surfactant system, and oleic acid as oil phase. Eight microemulsions-selected from the 1.25/8.75 oil/surfactants ratio, along the water dilution line (from 20 to 56% w/w)-were characterized in terms of rheological behavior, optical properties via polarized microscopy, and supramolecular structure using X-ray scattering. Then, these formulations were loaded with imiquimod and the uptake and distribution into the skin was evaluated on full-thickness porcine skin. X-ray scattering experiments revealed the presence of disconnected drops in the case of microemulsion with 20% water content. Diluting the system up to 48% water content, the structure turned into an interconnected lamellar microemulsion, reaching a proper disconnected lamellar structure for the highest water percentages (52-56%). Upon water addition, also the rheological properties changed from nearly Newtonian fluids to gel-like structures, displaying the maximum of viscosity for the 48% water content. Skin uptake experiments demonstrated that formulation viscosity, drug loading, and surfactant concentration did not play an important role on imiquimod uptake into the skin, while the skin penetration was related instead to the microemulsion mesostructure. In fact, drug uptake became enhanced by locally lamellar interconnected structures, while it was reduced in the presence of disconnected structures, either drops or proper lamellae. Finally, the data demonstrated that mesostructure also affects the drug distribution between the epidermis and dermis. In particular, a significantly higher dermal accumulation was found when disconnected lamellar structures are present, suggesting the possibility of tuning both drug delivery and localization into the skin by modifying microemulsions composition.

Docosahexaenoic acid triglyceride-based microemulsions with an added dendrimer – Structural considerations

Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compounds are water-insoluble and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future.The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water dilution line using electron paramagnetic resonance and pulsed-gradient spin-echo NMR along with other analytical techniques.The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water dilution. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants.In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface.

A novel topical targeting system of caffeine microemulsion for inhibiting UVB-induced skin tumor: characterization, optimization, and evaluation.

The purpose of the present study was to develop an optimal microemulsion (ME) formulation as topical nanocarrier of caffeine (CAF) to enhance CAF skin retention and subsequently improve its therapeutic effect on UVB-induced skin carcinogenesis. The pseudo-ternary phase diagram was developed composing of Labrafil M 1944 CS as oil phase, Cremophor EL as surfactant, tetraglycol as cosurfactant, and water. Four ME formulations at water content of 50, 60, 70, and 80% were prepared along the water dilution line of oil to surfactant ratio of 1:3 and characterized in terms of morphology, droplet size, and electric conductivity. A gel at the same drug loads (1%, w/w) was used as control. Ex vivo skin permeation studies were conducted for ME optimization. The optimized formulation (ME4) was composed of 5% (w/w) Labrafil M 1944 CS, 15% (w/w) Smix (2/1, Cremophor EL and tetraglycol), and 80% (w/w) aqueous phase. The skin location amount of CAF from ME4 was nearly 3-fold higher than control (P < 0.05) with improved permeated amount through the skin. The skin targeting localization of hydrophilic substance from ME4 was further visualized through fluorescent-labeled ME by a confocal laser scanning microscope. In pharmacodynamics studies, CAF-loaded ME4 was superior in terms of increasing apoptotic sunburn cells (P < 0.05) as compared with control. Overall results suggested that the ME4 might be a promising vehicle for the topical delivery of CAF.

Water solubilization capacity of pharmaceutical microemulsions based on Peceol®, lecithin and ethanol

Biocompatible microemulsions composed of Peceol®, lecithin, ethanol and water developed for encapsulation of hydrophilic drugs were investigated. The binary mixture Peceol®/ethanol was studied first. It was shown that the addition of ethanol to pure Peceol® has a significant fluidifying and disordering effect on the Peceol® supramolecular structure with an enhancement in water solubilization. The water solubilization capacity was improved by adding lecithin as a third component. It was then demonstrated that the ethanol/lecithin weight ratio played an important role in determining the optimal composition in term of water solubilization efficiency, a necessary property for a nutraceutical or pharmaceutical application. The optimal ethanol/lecithin weight ratio in the Peceol® rich region was found to be 40/60. Combination different techniques such as SAXS, fluorimetry, rheology and conductivity, we analyzed the water uptake within the microemulsion taking into account the partitioning of ethanol between polar and apolar domains. This ethanol distribution quantified along a water dilution line has a major effect on microemulsion properties.

High accuracy NMR chemical shift corrected for bulk magnetization as a tool for structural elucidation of dilutable microemulsions. Part 1 – Proof of concept

In microemulsions, changes in droplet size and shape and possible transformations occur under various conditions. They are difficult to characterize by most analytical tools because of their nano-sized structure and dynamic nature. Several methods are usually combined to obtain reliable information, guiding the scientist in understanding their physical behavior. We felt that there is a need for a technique that complements those in use today in order to provide more information on the microemulsion behavior, mainly as a function of dilution with water. The improvement of NMR chemical shift measurements independent of bulk magnetization effects makes it possible to study the very weak intermolecular chemical shift effects.In the present study, we used NMR high resolution magic angle spinning to measure the chemical shift very accurately, free of bulk magnetization effects. The chemical shift of microemulsion components is measured as a function of the water content in order to validate the method in an interesting and promising, U-type dilutable microemulsion, which had been previously studied by a variety of techniques. Phase transition points of the microemulsion (O/W, bicontinuous, W/O) and changes in droplet shape were successfully detected using high-accuracy chemical shift measurements. We analyzed the results and found them to be compatible with the previous studies, paving the way for high-accuracy chemical shifts to be used for the study of other microemulsion systems.We detected two transition points along the water dilution line of the concentrate (reverse micelles) corresponding to the transition from swollen W/O nano-droplets to bicontinuous to the O/W droplets along with the changes in the droplets’ sizes and shapes.The method seems to be in excellent agreement with other previously studied techniques and shows the advantage of this easy and valid technique.

Structure-activity relationship of a u-type antimicrobial microemulsion system.

The structure-activity relationship of a U-type antimicrobial microemulsion system containing glycerol monolaurate and ethanol at a 1∶1 mass ratio as oil phase and Tween 20 as surfactant were investigated along a water dilution line at a ratio of 80∶20 mass% surfactant/oil phase, based on a pseudo-ternary phase diagram. The differential scanning calorimetry results showed that in the region of up to 33% water, all water molecules are confined to the hydrophilic core of the reverse micelles, leading to the formation of w/o microemulsion. As the water content increases, the water gains mobility, and transforms into bicontinuous in the region of 33–39% water, and finally the microemulsion become o/w in the region of above 39% water. The microstructure characterization was confirmed by the dynamic light scattering measurements and freeze-fracture transmission electron microscope observation. The antimicrobial activity assay using kinetics of killing analysis demonstrated that the microemulsions in w/o regions exhibited relatively high antimicrobial activity against Escherichia coli and Staphylococcus aureus due to the antimicrobial oil phase as the continuous phase, while the antimicrobial activity started to decrease when the microemulsions entered the bicontinuous region, and decreased rapidly as the water content increased in the o/w region, as a result of the dilution of antimicrobial oil droplets in the aqueous continuous phase.

Microstructure characterization of a food-grade U-type microemulsion system by differential scanning calorimetry and electrical conductivity techniques

The microstructure transitions of a food-grade U-type microemulsion system containing glycerol monolaurate and propionic acid at a 1:1 mass ratio as oil phase and Tween 80 as surfactant were investigated along a water dilution line at a ratio of 80:20mass% surfactant/oil phase, based on a previously studied phase diagram. From the water thermal behaviours detected by differential scanning calorimetry, three structural regions are identified along the dilution line. In the first region, all water molecules are confined to the water core of the reverse micelles, leading to the formation of w/o microemulsion. As the water content increases, the water gains mobility, transforms into bicontinuous in the second region, and finally the microemulsion become o/w in the third region. The thermal transition points coincide with the structural phase transitions by electrical conductivity measurements, indicating that the structural transitions occur at 35 and 65mass% of water along the dilution line.

Phase Diagrams, Density, and Viscosity for the Pseudoternary System of {Propan-2-yl Tetradecanoate (IPM) (1) + [Tween 80 (21) + Propan-1-ol (22)] (2) + Water (3)}

In this work, a microemulsion system composed of propan-2-yl tetradecanoate (IPM) as oil, polyoxyethylene (20) sorbitan monooleate (Tween 80) as surfactant, propan-1-ol as cosurfactant, and water as the hydrophilic phase has been prepared. The pseudoternary phase diagram of {IPM (1) + [Tween 80 (21) + propan-1-ol (22)] (2) + water (3)} at 303.15 K has been constructed at a constant surfactant to cosurfactant mass ratio of 0.5:1. The phase diagram shows the area of microemulsion. Densities and viscosities were measured in the microemulsion area along three water dilution lines. A maximum viscosity is observed along the water dilution line, which indicates a structural transition from water-in-oil, to a bicontinuous state, and then inversion, to the state of oil-in-water.

Investigation of microemulsion microstructures and their relationship to transdermal permeation of model drugs: Ketoprofen, lidocaine, and caffeine

In this study, microemulsion microstructures, key formulation variables, and their relationship to drug transdermal permeation enhancement were investigated. A microemulsion system with high water soluble capacity was developed, using isopropyl myristate, Labrasol, and Cremophor EL as oil, surfactant, and co-surfactant, respectively. The microstructures of the microemulsions were characterized by a combination of techniques including electrical conductivity measurement (EC), differential scanning calorimetry (DSC), electro-analytical cyclic voltammetry (CV), dynamic light scattering (DLS). Three microemulsion formulations with the model drugs at water contents of 20%, 40%, and 70% representing the microstructures of W/O, Bi-continuous, and O/W were prepared along the water dilution line of oil to surfactant ratio of 1/9. Skin permeation of hydrophobic and hydrophilic model drugs, ketoprofen, lidocaine, and caffeine in the microemulsion formulations was studied using Franz-cells and dermatomed porcine skin. Permeation of all drugs from microemulsions was enhanced significantly compared with the control propylene glycol formulation. The drug permeation flux and the cumulative permeation amount after 24h increased with water content in the microemulsions, thus correlated to the formulation microstructures of W/O, Bi-continuous, and O/W. The permeation of lipophilic drugs ketoprofen and lidocaine increased with water content in a more pronounced manner, which seemed to follow an exponential growth trend, while the permeation of hydrophilic drug caffeine appeared to increase linearly. Additionally, at the same water content, increasing oil content led to higher ketoprofen permeation.

Celecoxib Solubilization in Nonionic Microemulsions

In this study, we report on the solubilization of celecoxib, a pharmaceutical active ingredient in the U-type microemulsions formulated using sucrose monolaurate and peppermint oil. Ethanol was used as the cosurfactant. The aqueous phase consisted of water + propylene glycol at a weight ratio equals two. The solubilization capacity of celecoxib in the formulated microemulsions along the water dilution line N60 where the surfactant/oil/ethanol weight ratio equals 3/1/1 is many times higher than in either the oil or the aqueous phase. The solubilized celecoxib does not affect the extent of water solubilization in the microemulsions. The celecoxib solubilization capacity decreases with the increase in the water content. We evaluated the microemulsions dilution and interfacial factors contributing to the celecoxib solubilization along the N60 dilution line. It was found that the dilution factor is dominant in determining the solubilization capacity of celecoxib when structural transitions are occurring. In an established microstructure, the interfacial factor is dominant. Structural transition of celecoxib loaded water-in-oil microemulsion to a bicontinuous phase and to oil-in-water droplets were identified using SAXS measurements along the N60 dilution line. It was found that below 30 wt% aqueous phase content the water-in-oil microemulsions are present, the transition between the water-in-oil to bicontinuous and then to oil-in water microemulsions occur at 30 and 75 wt% aqueous phase, respectively. SAXS measurements demonstrated that the drug effects the structure of microemulsion droplets and forms “ill-defined structures,” probably less spherical. Yet, the overall droplet sizes at the high dilutions did not change very much. The results demonstrate that the solubilized drug affects the transition from bicontinuous to water-in-oil microemulsions. The hydrodynamic radius of the drug loaded microemulsions at 80 and 90 wt% aqueous phase content was determined by dynamic light scattering.

Enhanced Percutaneous Permeability of Diclofenac Using a New U-Type Dilutable Microemulsion

Enhanced systemic absorption in vivo and percutaneous penetration in vitro was demonstrated after transdermal administration of diclofenac sodium formulated in U-type microemulsion. Diclofenac sodium was solubilized in a typical four-component system consisting of an oil, polyoxyethylene-10EO-oleyl alcohol (Brij 96V) as the surfactant, and 1-hexanol along water dilution line W46 (40 wt % surfactant and 60 wt % oil phase before water titration).Viscosity and small angle X-ray scattering measurements have evidenced bicontinuous structures within water fractions of 0.25 and 0.5 along the dilution line. Self-diffusion NMR studies showed that drug molecules accumulated in the interfacial film and, to some extent, dissolved in the oil. Relative to a commercial macro-emulsion cream (Voltaren® Emulgel®), microemulsions containing paraffin oil or isopropyl myristate increased the in vivo transdermal penetration rate of diclofenac by two order of magnitude, whereas the rat plasma levels were increased by one order of magnitude. The in vitro data obtained from excised rat skin were comparable to the in vivo results, but suffered from discrepancies from the ideal in vivo-in vitro correlation, which might be explained by optimal in vitro conditions of perfusion and hydration. It has also been found that when jojoba oil is formulated as the oil phase in the microemulsion, the penetration rate of the drug decreases significantly. Based on the three-dimensional structure of jojoba oil, the wax is presumed to prevent the drug from being freely diffused into the skin while migrating from the interfacial film into the continuous oil phase.

Electrostastic Control of Spontaneous Curvature in Catanionic Reverse Micelles

By means of small-angle neutron scattering and conductivity measurements, we study the microstructure of octylammoniumoctanoate/octane/water catanionic reverse microemulsions with an excess of anionic or cationic surfactant. Increasing the surface charge makes the microemulsion able to incorporate much more water than in the neutral case, up to 10 water molecules per surfactant. Even with charges in the surfactant film, wormlike micelles are present in the microemulsion domain. Along water dilution lines, the classical rod-to-sphere transition due to the minimization of the curvature energy of the rigid surfactant film is observed. When temperature is decreased, a re-entrant phase transition associated with the liquid-gas equilibrium of attractive cylinders is observed. Using the framework of the Tlusty-Safran theory, attraction could originate from junctions between wormlike reverse micelles. In any case, the spontaneous curvature of the catanionic surfactant film depends on both the temperature and the net charge, whatever the sign of the latter.

Improved solubilization of Celecoxib in U-type nonionic microemulsions and their structural transitions with progressive aqueous dilution

Celecoxib (clxb) is an important drug for treatment of rheumatoid arthritis and osteoarthritis by specifically inhibiting the enzyme cyclooxygenase-2 (COX-2). Clxb is a type 2 drug characterized by low water solubility (<5 μg/ml) and fast transmembrane transport. The present formulations require high dosage since the transmembrane transport fluctuates and is very difficult to control. Dissolving the drug within an oil phase was not practical since its dissolution was very small and its dispersion in water was impossible. In our recent studies, we learned to construct U-type phase diagrams and to formulate reverse microemulsions (oil-based concentrates) that are progressively and fully dilutable with aqueous phase. In the present study, we solubilized clxb in nanostructures of reverse micelles of U-type nonionic microemulsions that consisted of R(+)-limonene, alcohol, propylene glycol (PG), and hydrophilic surfactant (Tween 60). The solubilization capacity of the drug in these systems is many times higher than in either the oil or the aqueous phase. The clxb solubilized microemulsions are fully diluted with aqueous phase without phase separation. The solubilization capacity decreases as the water content increases. Electrical conductivity, viscosity, and self-diffusion (SD) coefficients of the microemulsion components were measured along a suitable water dilution line. The three major microemulsion regions were detected and the transitions between the W/O to bicontinuous phase and from this phase to the O/W droplets were identified (at 30 and 70 wt% aqueous phase, respectively). From the SD coefficients, it was found that the drug is initially solubilized at the interface of the W/O droplets and there are no significant structural changes. The transition to a bicontinuous phase occurs at the same water content as in the empty (i.e., without drug) system. From the viscosity profiles, we concluded that the drug affects the structure of the bicontinuous phase as reflected in the water content at which the oil-continuous network is destroyed and full inversion occurs (50 vs 55 wt% in the drug-loaded system). Upon further dilution the drug remains solubilized at the interface and is oriented with its hydrophilic part facing the water, and is strongly affects the inversion to O/W droplets. From Small Angle X-ray Scattering (SAXS) measurements we learned that the drug effects the structure of microemulsion droplets and forms “ill-defined structures,” probably less spherical. Yet, the overall droplet sizes at the high dilutions did not change very much.

Phase transition induced bywater dilution in phospholipid U-type food-grade microemulsions studied by DSC

In this study we used differential scanning calorimetry to clarify the role of water activity within the nano-droplets, and to explore phase transitions in novel phospholipids based fully dilutable food-grade microemulsions. The microstructure transitions were investigated along two water dilution lines (50:50 and 80:20 mass% surfactant mixture/oil phase). From the water thermal behavior we learned that three structural regions can be identified along the water dilution lines. The thermal transition points coincide with the structural phase transition of the microemulsions as measured by other methods (electrical conductivity and SD-NMR measurements). The structural transitions were detected at 20 and 45 mass% of water along dilution line 55, where along dilution line 82 it occurs at 40 and 50 mass% of water. The microemulsions along dilution line 82 seem to have more compact surfactant packing film, thus the film has stronger resistance to transformation upon dilution, resulting in a smaller bicontinuous region than the one formed at dilution line 55. The difference in phase transition point can be used for triggering the release of future solubilizate.

Effect of 1-butanol on the microstructure of lecithin/water/tripalmitin system

Warm microemulsions based on lipids characterized by a melting point over 50 °C have been successfully used as starting matrix in a quenching process to obtain solid lipid nanoparticles (SLN). In this work, we have investigated the effect of 1-butanol (B) on the phase behavior of the lecithin (LCT)/water (W)/tripalmitin (TP) system at 70 °C. The study has been carried out at LCT/B = 1 (weight ratio). Emulsion and liquid crystalline phase regions have been observed in the ternary phase diagram, while the presence of 1-butanol in the LCT/W/B/TP system allows the formation of a wide area of liquid isotropic phase from the whole (LCT + B)/TP binary axis up to 37 wt% of water. The microstructure of this isotropic phase has been investigated by means of 1H NMR PGSE technique. The self-diffusion coefficients of the different components along oil and water dilution lines indicate a microstructural organization characterized by a highly connected water in oil domains.

Phase Behavior of the Lecithin/Water/Isooctane and Lecithin/Water/Decane Systems

The isothermal pseudo-ternary-phase diagram was determined at 25 degrees C for systems composed oflecithin, water, and, as oil, either isooctane or decane. This was accomplished by a combination of polarizing microscopy, small-angle X-ray scattering, and NMR techniques. The lecithin-rich region of the phase diagram is dominated by a lamellar liquid-crystalline phase (Lalpha). For lecithin contents less than 60% and low hydration (mole ratio water/lecithin = W0 < 5.5), the system forms a viscous gel of branched cylindrical reverse micelles. With increase in the water content, the system phase separates into two phases, which is either gel in equilibrium with essentially pure isooctane (for lecithin < 25%) or a gel in equilibrium with Lalpha (for lecithin > 25%). These two-phase regions are very thin with respect to water dilution. For 8 < W0 < 54 very stable water-in-oil emulsions form. It is only after ripening for more than 1 year that the large region occupied by the emulsion reveals a complex pattern of stable phases. Moving along water dilution lines, one finds (i) the coexistence of gel, isooctane and Lalpha, (ii) equilibrium between reverse micelles and spherulites, and, finally, (iii) disconnected reverse micelles that fail to solubilize water for W0 > 54. This results in a Winsor II phase equilibrium at low lecithin content, while for lecithin > 20% the neat water is in equilibrium with a reverse hexagonal phase and an isotropic liquid-crystalline phase. The use of the decane as oil does not change the main features of the phase behavior.