Unit cell structure of water-filled monoolein in inverted hexagonal mesophase in the presence of incorporated tricaprylin and entrapped lysozyme.

Molecular dynamics (MD) was employed by means of a specific simulation protocol to investigate the equilibrium structure at 25 °C of the hexagonal inverted (HII) mesophase composed from water, 1-monoolein (GMO), and tricaprylin, with or without entrapped lysozyme. Based on robust and fast MD simulations, the study provides a comprehensive analysis and visualization of the local structure of HII mesophase containing admixtures. The most important physical insight is the possibility to observe the strong self-recovery capacity of the GMO layer, which allows the HII mesophase tubes to reorganize and host lysozyme molecules with a size bigger than the diameter of the water channel. This is a direct message to the experimenters that the HII mesophase has the potential to host molecules larger than the diameter of the water channel. Collective character of the interlipid interactions is outlined, which is not affected by the presence of the cargo and may be the reason for the efficient GMO reorganization. Another important result is the possible explanation of the role of triacylglycerols on the low-temperature stabilization of the HII mesophase. The analysis shows that despite the low amount of tricaprylin, its molecules prevent the extreme inclination of the lipid tails and thus optimize the alignment capacity of the lipid tails layer. The study also reveals that the packing frustration does not depend on the temperature and the presence of admixtures. Hence, it might be numerically defined as a universal invariant parameter of a stable HII mesophase composed of a certain lipid.

Heterogeneous micellar solubilization within lyotropic liquid crystals interfaces.

The solubilization of sodium diclofenac (Na-DFC) in a glycerol monooleate-based emulsion triggers series of structural changes. Incorporation of Na-DFC, leads to formation of a reverse hexagonal mesophase between 2 and 5 wt% Na-DFC. Between 6 and 9 wt% Na-DFC, the hexagonal symmetry gradually transitions to a disordered lamellar mesophase. These structural shifts impact the system's storage modulus, structuring enthalpy, and structural diffusivity. Despite these transitions, the driving force for Na-DFC release remains consistent, leading to hypothesize that the interfacial structure remains unchanged during Na-DFC release. The nano-structural modifications imposed by the Na-DFC load and release were assessed by small-angle X-ray diffraction (SAXD), spin-probe electron paramagnetic resonance (EPR), and nuclear quadrupole resonance (NQR). The selective solubilization of Na-DFC was demonstrated by SAXD peak fittings, revealing an increase of hexagonally oriented rods at the expense of non-oriented micelles, rather than gradual micellar elongation. Computation of the EPR spectra also showcased the selective solubilization of Na-DFC at an enhanced free energy interface (γ), evidenced by step-wise variations in polarity, microviscosity, and order parameters. Additionally, NQR analysis highlighted a higher anisotropy for sodium compared to deuterium, linking the selective solubilization of Na-DFC to heterogeneous structural transformations. These findings underscore the heterogeneous nature of solubilization-release processes, driven by locally increased micellar free energy. Consequently, the loaded Na-DFC interfaces maintain a constant γ, ensuring a consistent release driving force despite the structural transitions affecting the matrix. The ability to selectively solubilize guest molecules may herald a new era in the utilization of selective molecular interfacial loading.

Molecular dynamics approach to water structure of H(II) mesophase of monoolein.

The goal of the present work is to study theoretically the structure of water inside the water cylinder of the inverse hexagonal mesophase (H(II)) of glyceryl monooleate (monoolein, GMO), using the method of molecular dynamics. To simplify the computational model, a fixed structure of the GMO tube is maintained. The non-standard cylindrical geometry of the system required the development and application of a novel method for obtaining the starting distribution of water molecules. A predictor-corrector schema is employed for generation of the initial density of water. Molecular dynamics calculations are performed at constant volume and temperature (NVT ensemble) with 1D periodic boundary conditions applied. During the simulations the lipid structure is kept fixed, while the dynamics of water is unrestrained. Distribution of hydrogen bonds and density as well as radial distribution of water molecules across the water cylinder show the presence of water structure deep in the cylinder (about 6 Å below the GMO heads). The obtained results may help understanding the role of water structure in the processes of insertion of external molecules inside the GMO∕water system. The present work has a semi-quantitative character and it should be considered as the initial stage of more comprehensive future theoretical studies.

NMR chromatography using microemulsion systems.

NMR spectroscopy is an excellent tool for structural analysis of pure compounds. However, for mixtures, it performs poorly because of overlapping signals. Diffusion ordered NMR spectroscopy (DOSY) can be used to separate the spectra of compounds with widely differing molecular weights, but the separation is usually insufficient. NMR "chromatographic" methods have been developed to increase the diffusion separation but these usually introduced solids into the NMR sample that reduce resolution. Using nanostructured dispersed media, such as microemulsions, eliminates the need for suspensions of solids and brings NMR chromatography into the mainstream of NMR analytical techniques. DOSY was used in this study to resolve spectra of mixtures with no increase in line-width as compared to regular solutions. Components of a mixture are differentially dissolved into the separate phases of the microemulsions. Several examples of previously reported microemulsions and those specifically developed for this purpose were used here. These include a fully dilutable microemulsion, a fluorinated microemulsion, and a fully deuterated microemulsion. Log(diffusion) difference enhancements of up to 1.7 orders of magnitude were observed for compounds that have similar diffusion rates in conventional solvents. Examples of commercial pharmaceutical drugs were also analyzed via this new technique, and the spectra of up to six components were resolved from one sample.

Solubilization of vitamin E into H(II) LLC mesophase in the presence and in the absence of vitamin C.

The synergistic solubilization of two major hydrophilic (vitamin C, ascorbic acid, AA) and lipophilic (vitamin E, D-alpha-tocopherol, VE) antioxidants within reverse hexagonal (H(II)) mesophases is reported. The H(II) mesophases are composed of monoolein (GMO)/VE/AA/water. A wide range of VE concentration was examined (on the expense of GMO concentrations) while the AA and water concentrations remained constant (4 and 12.5 wt %, respectively) in order to expand the H(II) mesophase. SAXS and DSC combined with ATR-FTIR techniques were utilized to study the interactions between each solubilizate and the H(II) component that enabled the synergistic accommodation of the hydrophilic and hydrophobic molecules. It was revealed that up to 27 wt % VE solubilized within the H(II) mesophase. This hydrophobic additive localized at the lipophilic GMO tail region solvating the surfactant tails, thereby enabling the formation of the H(II) structure. As a result, the lattice parameter and the melting point of the hydrophobic tails decreased. Above 27 wt % VE (up to 33 wt %), once the GMO lipophilic region was homogenously solvated, additional VE molecules located closer to the interface. At this range of concentrations, new hydrogen bonds between O-H groups of VE and O-H groups of GMO were formed. Once 35 wt % VE was introduced, the H(II) structure transformed to face-centered reverse micellar cubic phase (Fd3m, Q(227)).

Structural rearrangements and interaction within H(II) mesophase induced by cosolubilization of vitamin E and ascorbic acid.

We investigated the effect of ascorbic acid (AA) cosolubilized with vitamin E (VE) on reverse hexagonal (H(II)) mesophase. The H(II) phase comprises monoolein (GMO)/d-alpha-tocopherol (VE) in a ratio of 90/10 by weight and 12.5 wt % water. The macrostructural characteristics of this system were determined by polarized light microscopy and small-angle X-ray scattering measurements. We used differential scanning calorimetry and attenuated total reflectance Fourier transform infrared to characterize the microstructure, the vibration of the functional groups, and the location of the AA guest molecule. AA was incorporated to the system in two steps: 1-4 wt % AA and 5-6 wt % AA. We compared this system to one containing tricaprylin as the oil phase, as previously reported. These measurements revealed that AA is localized first in the water rich-core and in the interface, and acts as a chaotropic molecule that decreases the water melting point. When a larger quantity of AA (5-6 wt %) is added, the system is saturated, and the AA is located in the inner cylinder and manifested by more moderate distortion. The addition of AA also causes alteration in the behavior of the GMO hydrocarbon chains and makes them more flexible. Further addition of AA caused the GMO hydrocarbon chain to be more solvated by the VE hydrocarbon chain and enabled additional migration of VE; hence a decrease in the hydrophobic melting temperature occurred (similar to tricaprylin). Increasing the amount of AA weakened the bonding between the GMO and water and created new bonds between AA and GMO and AA with water.

Concentration- and temperature-induced effects of incorporated desmopressin on the properties of reverse hexagonal mesophase.

In this paper we report on the solubilization of desmopressin, as a model for peptide drugs, into reverse hexagonal (H(II)) liquid crystals. Concentration- and temperature-induced interactions of desmopressin, as well as the conformation of the peptide, were studied using small-angle X-ray scattering, ATR-FTIR spectroscopy, SD-NMR, and rheological measurements. A considerable increase (up to 6 A) in the lattice parameter of the mesophases was obtained upon incorporation of the peptide. According to the ATR-FTIR analysis, the chaotropic effect of peptide embedment was assigned to its interactions with hydroxyls of monoglyceride in the outer interface region. These interactions had only a minor influence on the conformation of the peptide; weakening or opening the gamma-turns resulted in partial binding of the peptide's free carbonyls to monoolein. Temperature-dependent SAXS measurements displayed a chaotropic destabilizing effect of desmopressin on the structure, shifting toward the lower temperature H(II)-L(2) structural transition. Temperature increase resulted in an increase of the domain size in the presence of the peptide, in contrast to the trend observed in the empty mesophase. SD-NMR analysis enabled distinguishing between two factors impeding the diffusion of the peptide: the restriction of motion due to the geometrical constrain of diffusion within the water tubes, and the interactions of the guest molecule with monoglyceride. The onset of the critical behavior at 45 degrees C was found to be significant, indicating considerable weakening of the monoglyceride and desmopressin interactions and the destabilizing effect of the peptide on the mesophase above this temperature. Similar temperature-dependent behavior was revealed by rheological measurements displaying the same onset of the critical behavior. It was demonstrated by Franz diffusion cell measurements that hexagonal mesophases can potentially be used as delivery vehicles for sustained delivery of desmopressin.

Molecular interactions in lyotropic reverse hexagonal liquid crystals: a dielectric spectroscopy study.

A dielectric study of reverse hexagonal mesophases (HII) is presented. Conducted in the frequency range 0.01-1 MHz and temperature range 293

Formation and characterization of ordered bicontinuous microemulsions.

Ordered bicontinuous microstructures formed in a fully water-dilutable, pseudoternary unique nonionic microemulsion were obtained and characterized. The concentrate contained a mixture of triacetin/d-alpha-tocopherol acetate/ethanol/Tween 60. Upon dilution, the concentrate was transformed from a reversed micellar system to oil-in-water microemulsion droplets. The transformation occurred through an intermediate phase of ordered bicontinuous structures. The factors that governed the construction of this unique phase, and its physical and structural properties, were characterized in detail. The techniques used included small angle X-ray scattering (SAXS), self-diffusion and quantum filtered NMR, differential scanning calorimetry, rheology measurements, electrical conductivity, and dynamic light scattering. This mesophase displays microemulsion properties along with some characteristics of lyotropic liquid crystals (but is not a mixture of the two). Similar to microemulsions, the structures were transparent and spontaneously formed and exhibited thermodynamic stability. Yet, unlike microemulsions, they showed short-range order at room temperature. Additionally, the microstructures exhibited non-Newtonian flow behavior, characteristic of lamellar structures. The bicontinuous ordered microemulsions were obtained upon heating (to 25 degrees C) from the lamellar phase existing at low temperatures (5 degrees C). The main feature governing the bicontinuous mesophase formation was the amphiphilic nature of oil blends composed of d-alpha-tocopherol acetate and triacetin. The oils functioned as cosurfactants, altering the packing parameter of the surfactant and leading to the construction of bicontinuous structures with short-range order. These unique structures might have drug or nutraceutical delivery advantages.

Characterization of the nonionic microemulsions by EPR. I. Effect of solubilized drug on nanostructure.

The effect of the solubilized model drug, carbamazepine, on the internal structure of fully dilutable nonionic microemulsions was examined for the first time using electron paramagnetic resonance (EPR). Systems containing different surfactant to oil ratios, at two different pH values (4.6 and 8.5), with continuous dilution implementing structural transformations (micellar solution-W/O-bicontinuous-O/W) were investigated. The internal order, micropolarity, and microviscosity were scrutinized utilizing pH-dependent amphiphilic probe 5-doxylstearic acid (5-DSA). In the basic environment, the probe explored the vicinity of the surfactant head region; the deeper hydrophobic region of the surfactant tails was investigated in the acidic milieu. The study demonstrated that the EPR technique enables efficient monitoring of structural changes and examination of drug influence on structure in surfactant-poor systems. Lower order and microviscosity values were obtained in surfactant-poor systems in comparison to surfactant-rich systems. The drug functioned as a spacer of the surfactant molecules or as a cosurfactant depending on the formed microemulsion structure and the surfactant to oil ratio. The structural changes, pH variation, and presence of the drug did not alter the polarity parameter, indicating that the probe most likely does not sense a water environment in any of the examined systems. Under the basic conditions, higher microviscosity and order values were obtained in comparison to those at low pH, suggesting a higher order packing of the surfactant chains near the surfactant heads. The structural changes initiated in the vicinity of the surfactant heads, therefore, are more apparent in the basic environment. The ability to control and monitor the intramicellar interactions within drug carrier systems may be of significant interest for understanding the kinetics of drug release.

Characterization of nonionic microemulsions by EPR. Part II. The effect of competitive solubilization of cholesterol and phytosterols on the nanostructure.

One of the theories for the reduction of cholesterol (CH) in the blood stream by the consumption of phytosterols (PS) states that these two types of sterols compete for solubilization within the dietary mixed micelles (DMM). In this study, a fully dilutable nonionic microemulsion system was used as a model to explain a possible competitive solubilization mechanism of CH and PS molecules using an electron paramagnetic resonance (EPR) technique that reveals relevant intramicellar properties. The effect of the solubilized sterols on the structural changes occurring in the vicinity of the surfactant head groups or closer to the oil phase was examined by controlling the pH of the environment, which influences the probe locus between the surfactant molecules. The results indicate that the structure transformations in the surfactant layer closer to the vicinity of the head groups region are more pronounced than the structural changes occurring in the region between the surfactant tails closer to the oil phase, except for the oil-in-water (O/W) micelles region. The study also shows that when each of the sterols is solubilized alone, they occupy different solubilization sites within the microemulsion nanostructures, in comparison to their solubilization together. This behavior is most pronounced in 3:1 (wt ratio) CH/PS systems. The main conclusion is that cosolubilization of these sterols leads to competitive solubilization between the surfactant tails closer to the oil phase locus, where the CH molecules are pushed toward the interface by the PS molecules. This conclusion might better explain the competitive solubilization of the two sterols in the human digestive tract.

Potentiality of microemulsion systems in treatment of ophthalmic disorders: Keratoconus and dry eye syndrome - In vivo study.

Microemulsions are widely studied as potential ocular drug delivery vehicles. In the present study we show the versatility of possible use microemulsions as ocular delivery vehicle. The ME is loaded with a hydrophilic drug, riboflavin phosphate (RFP) and a lipophilic, docosahexaenoic acid in triglyceride form (TG-DHA), each separately. These drugs treat keratoconus and dry eye syndrome, respectively. The advantage of using ME loaded with RFP is in overcoming eye epithelium debridement during collagen cross-linking therapy for treatment of keratoconus. ME loaded with lipophilic TG-DHA provides convenient dosage in liquid aqueous form of administration of highly lipophilic TG-DHA, which is known as a protective molecule in dry eye syndrome. The capability of RFP-loaded MEs was demonstrated in terms of improvement of biomechanical strength of the rabbit cornea, as a result of successful penetration of RFP through the intact epithelium. TG-DHA-loaded microemulsion applied topically onto an eye with induced dry eye syndrome showed the significant relief of the dry eye condition.

Solubilization of nutraceuticals into reverse hexagonal mesophases.

The solubilization of four bioactive molecules with different polarities, in three reverse hexagonal (HII) systems has been investigated. The three HII systems were a typical reverse hexagonal composed of glycerol monooleate (GMO)/tricaprylin/water and two fluid hexagonal systems containing either 2.75 wt % Transcutol or ethanol as a fourth component. The phase behavior of the liquid crystalline phases in the presence of ascorbic acid, ascorbyl palmitate, D-alpha-tocopherol and D-alpha-tocopherol acetate were determined by small-angle X-ray scattering (SAXS) and optical microscopy. Differential scanning calorimetry (DSC) and Fourier-transform infrared (FT-IR) techniques were utilized to follow modifications in the thermal behavior and in the vibrations of different functional groups upon solubilizing the bioactive molecules. The nature of each guest molecule (in both geometry and polarity) together with the different HII structures (typical and fluids) determined the corresponding phase behavior, swelling or structural transformations and its location in the HII structures. Ascorbic acid was found to act as a chaotropic guest molecule, localized in the water-rich core and at the interface. The AP was also a chaotropic guest molecule with its head located in the vicinity of the GMO headgroup while its tail embedded close to the surfactant tail. D-alpha-tocopherol and D-alpha-tocopherol acetate were incorporated between the GMO tails; however, the D-alpha-tocopherol was located closer to the interface. Once Transcutol or ethanol was present and upon guest molecule incorporation, partial migration was detected.

Low viscosity reversed hexagonal mesophases induced by hydrophilic additives.

This study reports on the formation of a low viscosity H(II) mesophase at room temperature upon addition of Transcutol (diethylene glycol mono ethyl ether) or ethanol to the ternary mixture of GMO (glycerol monooleate)/TAG (tricaprylin)/water. The microstructure and bulk properties were characterized in comparison with those of the low viscosity HII mesophase formed in the ternary GMO/TAG/water mixture at elevated temperatures (35-40 degrees C). We characterized the role of Transcutol or ethanol as inducers of disorder and surfactant mobility. The techniques used were rheology, differential scanning calorimetry (DSC), wide- and small-angle X-ray scattering (WAXS and SAXS, respectively), NMR (self-diffusion and (2)H NMR), and Fourier transform infrared (FTIR) spectroscopies. The incorporation of either Transcutol or ethanol induced the formation of less ordered HII mesophases with smaller domain sizes and lattice parameters at room temperature (up to 30 degrees C), similar to those found for the GMO/TAG/water mixture at more elevated temperatures (35-40 degrees C). On the basis of our measurements, we suggest that Transcutol or ethanol causes dehydration of the GMO headgroups and enhances the mobility of the GMO chains. As a result, these two small molecules, which compete for water with the GMO polar headgroups, may increase the curvature of the cylindrical micelles and also perhaps reduce their length. This results in the formation of fluid H(II) structures at room temperature (up to 30 degrees C). It is possible that these phases are a prelude to the H(II)-L(2) transformation, which takes place above 35 degrees C.

Viability and permeability across Caco-2 cells of CBZ solubilized in fully dilutable microemulsions.

The purpose of this study was to evaluate the viability and permeability of carbamazepine (CBZ) solubilized in fully dilutable non-ionic microemulsions across Caco-2 cells used as a model for intestinal epithelium. Maximum solubilization capacity (SC) of CBZ was determined within water-in-oil (W/O), bicontinuous and oil-in-water (O/W) structures formed upon dilution. The effect of the nature of the oil phase, surfactant type, and the ratio between the oil phase and surfactant on the quantity of solubilized CBZ, droplets size, the viability of the cells and drug permeability was elucidated. We found that: (1) several fully dilutable microemulsions based on pharma-grade ingredients can be loaded with very significant amounts of CBZ, (2) W/O microemulsions (10wt% water) exhibit up to 3-fold higher solubilization capacity over the drug's solubility in oil (triacetin), (3) CBZ in the O/W microemulsions (80wt% water) exhibit up to 29-fold higher solubilization than in water, (4) the O/W droplets of the examined systems are 9-11nm in size, (5) the highest permeability was obtained in systems containing triacetin/alpha-tocopherol acetate/ethanol in 3/1/4wt% ratio as oil phase and Tween 60 as surfactant, (6) the replacement of alpha-tocopherol acetate by alpha-tocopherol inhibits CBZ release, (7) replacement of a saturated chain of Tween 60 by an unsaturated (Tween 80) or shorter chain (Tween 40) inhibited drug release, (8) the decrease in the oil phase to surfactant ratio leads to enhancement of drug release (dilution line 64>dilution line 73).

Competitive solubilization of cholesterol and phytosterols in nonionic microemulsions studied by pulse gradient spin-echo NMR.

The actual mechanism of cholesterol reduction by phytosterols is yet to be explored. One hypothesis states that cholesterol and phytosterols compete on the solubilization locus within gastric bile salt micelles. In this study competitive solubilization within microemulsions as vehicles for dietary intake of cholesterol and phytosterols was studied by pulse gradient spin-echo nuclear magnetic resonance. The loaded microemulsions undergo phase transitions as a function of dilution, the type of solubilized sterol, and the weight ratio of the cosolubilized sterols. Microemulsions containing 10-20 wt% of aqueous phase, show similar diffusivity of the oil and aqueous phases in all examined systems (excluding PS-loaded one) reflecting the minor influence of these solubilizates on the structure of the inner and the outer phases. The closeness of these structures enables the mobility of water molecules between them. Upon further dilution (>20 wt% aqueous phase), significant differences in decrease rate of the oil and increase of the water phases mobilities (occurring upon inversion), were detected within the studied systems. It was concluded that the solubilized sterols influence the structural transitions based on their location within the structures and their competitive solubilization. The phytosterols solubilized mostly in the continuous oil phase and between the surfactant tails. Cholesterol is solubilized in the vicinity of the surfactant headgroups and affects the surface curvature. In mixtures of cholesterol and phytosterols, structural changes are dictated mostly by the presence of the cholesterol.

Phosphatidylcholine embedded micellar systems: enhanced permeability through rat skin.

Micellar and microemulsion systems are excellent potential vehicles for delivery of drugs because of their high solubilization capacity and improved transmembrane bioavailability. Mixtures of propylene glycol (PG) and nonionic surfactants with sodium diclofenac (DFC) were prepared in the presence of phosphatidylcholine (PC) as transmembrane transport enhancers. Fully dilutable systems with maximum DFC solubilization capacity (SC) at pH 7 are presented. It was demonstrated that the concentrates underwent phase transitions from reverse micelles to swollen reverse micelles and, via the bicontinuous transitional mesophase, into inverted O/W microstructures. The SC decreases as a function of dilution. DFC transdermal penetration using rat skin in vitro correlated with SC, water content, effect of phospholipid content, presence of an oil phase, and ethanol. Skin penetration from the inverted bicontinuous mesophase and the skin penetration from the O/W-like microstructure were higher than that measured from the W/O-like droplets, especially when the micellar system containing the nonionic surfactant, sugar ester L-1695, and hexaglycerol laurate. PC embedded within the micelle interface significantly increased the penetration flux across the skin compared to micellar systems without the embedded PC at their interface. Moreover, the combination of PC with HECO40 improved the permeation rate (P) and shortened the lag-time (T(L)).

Controlling insulin release from reverse hexagonal (HII) liquid crystalline mesophase by enzymatic lipolysis.

In the present study we aimed to control insulin release from the reverse hexagonal (HII) mesophase using Thermomyces lanuginosa lipase (TLL) in the environment (outer TLL) or within the HII cylinders (inner TLL). Two insulin-loaded systems differing by the presence (or absence) of phosphatidylcholine (PC) were examined. In general, incorporation of PC into the HII interface (without TLL) increased insulin release, as a more cooperative system was formed. Addition of TLL to the systems' environments resulted in lipolysis of the HII structure. In the absence of PC, the lipolysis was more dominant and led to a significant increase in insulin release (50% after 8h). However, the presence of PC stabilized the interface, hindering the lipolysis, and therefore no impact on the release profile was detected during the first 8h. Entrapment of TLL within the HII cylinders (with and without PC) drastically increased insulin release in both systems up to 100%. In the presence of PC insulin released faster and the structure was more stable. Consequently, the presence of lipases (inner or outer) both enhanced the destruction of the carrier, and provided sustained release of the entrapped insulin.

Thermally induced fluid reversed hexagonal (H(II)) mesophase.

In the present study we characterized the microstructures of the Lc and HII phases in a glycerol monooleate (GMO)/tricaprylin (TAG)/water mixture as a function of temperature. We studied the factors that govern the formation of a low-viscosity HII phase at relatively elevated temperatures (>35 degrees C). This phase has very valuable physical characteristics and properties. The techniques used were differential scanning calorimetry (DSC), wide- and small-angle X-ray scattering (WAXS and SAXS, respectively), NMR (self-diffusion and (2)H NMR), and Fourier transform infrared (FTIR) spectroscopies. The reverse hexagonal phase exhibited relatively rapid flow of water in the inner channels within the densely packed cylindrical aggregates of GMO with TAG molecules located in the interstices. The existence of two water diffusion peaks reflects the existence of both mobile water and hydration water at the GMO-water interface (hydrogen exchange between the GMO hydroxyls and water molecules). Above 35 degrees C, the sample became fluid yet hexagonal symmetry was maintained. The fluidity of the HII phase is explained by a significant reduction in the domain size and also perhaps cylinder length. This phenomenon was characterized by higher mobility of the GMO, lower mobility of the water, and a significant dehydration process.

Improved solubilization of carbamazepine and structural transitions in nonionic microemulsions upon aqueous phase dilution.

Solubilization capacity and structural transformations in nonionic microemulsions characterized by a large continuous isotropic region forming dilutable self-assembled nanodroplets containing solubilized carbamazepine, were studied along dilution lines 73 and 82 (70 and 80 wt% surfactant and 30 and 20 wt% of oil phase, respectively). The preparations were based on pharma-grade ingredients, water, R-(+)-limonene, ethanol, propylene glycol, and Tween 60. Solubilization capacity (SC) of the drug was dependent on the microstructure of the microemulsion and on the surfactant-to-oil phase weight ratio. The SC in the concentrate (reversed micelles) was 15 times higher than its solubility in the oil. Transition of the W/O microemulsion to a bicontinuous phase and to O/W droplets were indentified by electrical conductivity, viscosity, SAXS, and SD-NMR measurements. Once the system is diluted to 90 wt% aqueous phase, the SC is 10 and 16-fold higher, along dilution lines 73 and 82, respectively, than in pure water. Being solubilized, carbamazepine serves as a cosurfactant therefore it affects the curvatures of the microstructures and consequently the boundaries of the structural regions and the transition points between the different phases. Dilutable microemulsions are promising new carbamazepine vehicles for oral intake.