Opaque Emulsion Research Articles

Phase Behavior of Non‐Ionic Surfactant‐Medium Chain Triglyceride‐Water Microemulsion Systems

AbstractMicroemulsion systems have garnered tremendous interest in the pharmaceutical sector for a variety of drug delivery applications. Non‐ionic surfactants are often the preferred surfactant class given their uncharged nature, enhanced oral safety profile, and generally regarded as safe status as compared to other surfactant classes (Myers, Surfactant science and technology, 2005, p. 29), (Malmsten, Handbook of microemulsion science and technology, 1999, p. 755), (Grove & Mullertz, Chapter 5‐liquid self‐microemulsifying drug delivery systems, 2007), (Liu et al., Water‐insoluble drug formulation, 2008), (Hauss, Advanced Drug Delivery Reviews, 2007, 59, pp. 667–676), (Balazs, Solubility, delivery and ADME problems of drugs and drug‐candidates, 2011, p. 68). In this work, the phase behavior and microemulsion formation potential of four commonly used non‐ionic surfactants, PEG‐40 hydrogenated castor oil, Poloxamer 188, Polysorbate 80, and d‐α‐tocopherol polyethylene glycol succinate were studied via ternary phase diagram (TPD) mapping using a medium chain triglyceride, Miglyol 812. Results indicated notable differences in phase behavior despite similarities in hydrophilic–lipophilic balance value (13–15). All surfactants produced Winsor Type I, oil‐in‐water microemulsions at water concentrations above 40% wt/wt. Winsor Type II water‐in‐oil microemulsions were difficult to obtain even at high oil concentrations of ≥70% wt/wt. Winsor III microemulsions, though rare, were generally obtained in the middle regions of the TPD between 10% and 30% wt/wt water while Winsor IV microemulsions dominated at high surfactant concentrations of ≥45% wt/wt. Opaque emulsion areas were particularly notable in wax state surfactants. Polysorbate 80 and PEG‐40 hydrogenated castor oil demonstrated a high degree of synergism as well as the largest oil‐in‐water (o/w) and water‐in‐oil (w/o) microemulsion formation potential rendering them suitable for a number of enteral and parenteral applications.

Microfluidic Optical Shutter Flexibly x-y Actuated via Electrowetting-on-Dielectrics with <20 ms Response Time

Tunable microoptics deals with devices of which the optical properties can be changed during operation without mechanically moving solid parts. Often a droplet is actuated instead, and thus tunable microoptics is closely related to microfluidics. One such device/module/cell type is an optical shutter, which is moved in or out of the path of the light. In our case the transmitting part comprises a moving transparent and electrically conductive water droplet, embedded in a nonconductive blackened oil, that is, an opaque emulsion with attenuation of 30 dB at 570 nm wavelength over the 250 μm long light path inside the fluid (15 dB averaged over the visible spectral range). The insertion loss of the cell is 1.5 dB in the “open shutter” state. The actuation is achieved via electrowetting-on-dielectrics (EWOD) with rectangular AC voltage pulses of 2·90 V peak-to-peak at 1 kHz. To flexibly allow for horizontal, vertical, and diagonal droplet movement in the upright x-y plane, the contact structures are prepared such that four possible stationary droplet positions exist. The cell is configured as two capacitors in series (along the z axis), such that EWOD forces act symmetrically in the front and back of the 60 nl droplet with a response time of <20 ms.

Surfactant-oil interactions overcoming physicochemical instability and insoluble praziquantel loading in soybean oil dispersions

Previous studies have reported the limited use of the insoluble ingredient praziquantel (PRZ) in liquid dispersions for the treatment of Schistosomiasis disease. Its interaction with oils used to produce pharmaceutical emulsions has not been reported. The effect of the composition of soybean oil dispersions on the phase behavior is carefully assessed in this study in order to produce stable emulsions that are able to overcome the drug dispersion in water. The mixture of polysorbate 80 (POL) and sorbitan monooleate (MON) (4:7, w/w) has stabilized the soybean oil in water under distinct conditions for 30days. The structural features and drug-loading capacity are assessed from eight liquid and opaque emulsion formulations selected in the phase-behavior diagram (oil phase range from 5% to 30% w/w and surfactants between 1% to 10% w/w). Even the samples with the highest soybean oil have proved to be stable liquid-like, Newtonian flow-type emulsions. The droplet size has been controlled in the range of 400nm to 1200nm, and the drug loading according to the composition of emulsions. The increase of the soluble drug fraction has ranged about 75 fold more than its water solubility. The feasibility and great potential of O/W soybean oil dispersion has been proved for PRZ delivery for the treatment of the Schistosomiasis disease.

Emulsion-mediated synthesis of hierarchical mesoporous-macroporous Al-Mg hydrotalcites

A new sol-gel method mediated by the use of paraffin emulsions is presented for the synthesis of hierarchical mesoporous-macroporous Al-Mg hydrotalcites. Prior to the synthesis, the construction of ternary diagrams for paraffin/surfactant/ethanol helped to identify the most suitable compositional synthesis domain. Two distinct regions, denoted L1 (transparent microemulsion) and L2 (opaque emulsion) were identified for low and high concentrations of paraffins, respectively. The ternary diagrams revealed some features: i) n-hexane (C6) had the smallest L2 region; ii) the high viscosity of n-octadecane (C18) did not allow control of phase separation, and iii) the most suitable paraffin for the use as the emulsifier was the intermediate-sized n-dodecane (C12). The use of paraffin in concentrations included in the L1 region did not contribute to the creation of pores, but the emulsion templating in the L2 region led to hierarchical porous hydrotalcites when were calcined up to 250 °C having enhanced textural properties and presenting mesopores and macropores with mean sizes of 0.02 and 1 μm, respectively. The slit-like shaped mesopores were caused by the partial exfoliation of hydrotalcite layers unordered packed around the emulsion droplets, while the macropores arose from voids left by the droplets after thermal treatment. The singular textural properties of the studied Al-Mg hierarchical porous hydrotalcites turns the emulsion mediated-synthesis a potential method to obtain more efficient catalysts to be used in process involving bulky molecules.

In Vitro Digestion of the Self-Emulsifying Lipid Excipient Labrasol® by Gastrointestinal Lipases and Influence of its Colloidal Structure on Lipolysis Rate

Labrasol(®) is a self-emulsifying excipient used to improve the oral bioavailability of poorly water-soluble drugs. It is a mixture of acylglycerols and PEG esters, these compounds being substrates for digestive lipases. The characterization of Labrasol(®) gastrointestinal lipolysis is essential for understanding its mode of action. Labrasol(®) lipolysis was investigated using either individual enzymes (gastric lipase, pancreatic lipase-related protein 2, pancreatic carboxyl ester hydrolase) or a combination of enzymes under in vitro conditions mimicking first the gastric phase of lipolysis and second the duodenal one. Specific methods for quantifying lipolysis products were established in order to determine which compounds in Labrasol(®) were preferentially hydrolyzed. Gastric lipase showed a preference for di- and triacylglycerols and the main acylglycerols remaining after gastric lipolysis were monoacylglycerols. PEG-8 diesters were also hydrolyzed to a large extent by gastric lipase. Most of the compounds initially present in Labrasol(®) were found to be totally hydrolyzed after the duodenal phase of lipolysis. The rate of Labrasol(®) hydrolysis by individual lipases was found to vary significantly with the dilution of the excipient in water and the resulting colloidal structures (translucent dispersion; opaque emulsion; transparent microemulsion), each lipase displaying a distinct pattern depending on the particle size. The lipases with distinct substrate specificities used in this study were found to be sensitive probes of phase transitions occurring upon Labrasol(®) dilution. In addition to their use for developing in vitro digestion models, these enzymes are interesting tools for the characterization of self-emulsifying lipid-based formulations.

Enzyme‐catalysed hydrolysis of phosphatidylcholine for the production of lysophosphatidylcholine

AbstractBackgroundProduction of lysophosphatidylcholine (LPC) via enzyme‐catalysed hydrolysis was studied. Three enzymes were employed to conduct the reactions at different temperatures. The starting material, phosphatidylcholine (PC), was dispersed in water (system A) and in ethanol (system B) to define the reaction mixture to carry out the trials.ResultsIt was found that the media employed and the type of biocatalyst (free or immobilized), clearly determine the kinetics of the reactions. PC was well dissolved in ethanol but an opaque emulsion was obtained when it was dissolved in water. Immobilized PLA1 and Novozym 435 were able to convert PC into LPC in ethanol, with yields of 50% and 58.51%, respectively, after 48 h at 50 °C. The highest degree of hydrolysis (70%) was reached with Lipase PS after 48 h at 60 °C in water.ConclusionsBoth reaction media enabled fairly good yields but water was better. The present work proposes a simple reaction scheme compared with other reports in the literature where different substrates, additives and polar solvents have been employed. LPC has interesting properties as a bioemulsifier, which led us to develop new methods for its production. © 2013 Society of Chemical Industry

Enhanced transmission with tunable Fano-like profile in magnetic nanofluids

We observe a Fano-like resonance in a magnetically polarizable nanofluid. Under an external magnetic field, the transmittance spectrum of a ferrofluid emulsion containing droplet size of ~220 nm shows an enhanced peak with a Fano-like profile, which is attributed to a localized waveguide resonance from random array of tubes with charged inner surface that are formed by the alignment of the droplets. Furthermore, by varying the magnetic field, the Fano profile is tuned and an opaque emulsion is turned into a transparent one. This finding may have interesting applications in tunable photonic devices.

Examination of phase transition behavior of ion group functionalized MPEG-b-PCL diblock copolymers

Thermogelling block copolymers are central to a variety of biomedical applications. Here, we examined the thermal phase transition behavior of the MPEG-b-PCL diblock copolymer (MC) with carboxyl (MC–COOH) and amine (MC–NH2) groups, and their salt forms (MC–COO−Na+ and MC–NH3+Cl−) at the chain ends of the PCL segment. All MC copolymers formed an opaque emulsion sol at room temperature when prepared as 20 wt% aqueous solutions. As the temperature increased from room temperature, a sol-to-gel transition was observed for MC, MC–COOH, and MC–NH2 copolymers, although not for their salt forms (MC–COO−Na+ and MC–NH3+Cl−). Introduction of a carboxyl and an amine group into the PCL segment decreased the crystallinity and hydrophobicity of the PCL block domains, which altered the onset temperature of gelation (the gel temperature range) and the maximum viscosity. We confirmed that the sol-to-gel phase transition behavior, which indicated the formation and destruction of a structured gel network of MC copolymers, depended on the crystallinity and hydrophobicity of the PCL domains in aqueous media.

Room-temperature decomposition of 2,2′-azobis(isobutyronitrile) in emulsion gels with and without silica

The decomposition of 2,2′-azobis(isobutyronitrile) (AIBN) at room temperature was studied in emulsion gels, with and without silica, using UV/visible spectroscopy. The emulsion gels consisted of toluene, AIBN, an aqueous solution of a surfactant (either hexadecyltrimethylammonium bromide, CTAB, or sodium dodecyl sulfate, SDS), and, in some cases, fumed silica. The AIBN compositions were determined in the opaque emulsion gels by converting them to transparent microemulsions. The decomposition rate constants for AIBN were determined to be 3.7 × 10 −8 s −1 ( ± 0.6 × 10 −8 s −1 ) for the emulsion gels and 10.2 × 10 −8 s −1 ( ± 1.3 × 10 −8 s −1 ) for the silica-containing emulsion gels. These rate constants were significantly greater than that in toluene solution, which, by our technique, is below our measurement threshold (effectively 0).

The Study of the Extraction of Surface-Active Component of a Binary Liquid from Model (“Cylindrical”) Droplets

The dissolution of the droplets of a chlorobenzene and isopropanol mixture in water that filled the Hele-Shaw vertical cell is experimentally studied. The choice of a cylindrical shape for droplets, thus providing only one free (lateral) surface, makes it possible to use the interference method to obtain quantitative characteristics of the studied process. Information on arising flows is obtained by examining the motion of opaque emulsion formed at the interface during the dissolution of a mixture. The interrelation between various mass transfer mechanisms in the droplet as a function of the initial concentration of a mixture and the time of dissolution is discussed.

MMA/DVB emulsion surface graft polymerization initiated by UV light.

Methyl methacrylate/1,2-divinylbenzene (MMA/DVB) in an opaque emulsion were successfully grafted onto the surface of polymeric substrate under the irradiation of UV light with benzophenone (BP) as a photoinitiator that was previously coated on the substrate surface. Monomer conversion, grafting efficiency, and grafting yields were determined by the gravimetric method. ATR-IR, AFM, and TEM were used to characterize the surface composition, to observe the topography of the grafted substrates, and to view inter-film colloid particles formed by cross-linking. The results reveal that, with the opaque MMA/DVB emulsion system and CPP film as substrate, the monomer conversion is in the range of 15-55%, the grafting efficiency is about 80%, the grafting yield reaches 5%, and the thickness of the graft layer can be controlled in the range 0.09-1.5 microm. Images of AFM show that the graft layer is piled up by nanoparticles (about 30-50 nm in diameter), which are linked together and tied to the substrate surface with covalent bonds. A possible model of surface graft polymerization including surface initiating, nucleation, and shish kebab growing is put forward to interpreting the above results.

Oil-in-water microemulsions from association structures of surfactant, water and aminosilicone polymer oil

The interaction of an aminosilicone polymer oil, a nonionic surfactant and water was examined by ternary phase diagram, spinning drop interfacial tension and particle size measurement of oil-in-water microemulsions resulting from a unique patented procedure to combine isotropic ternary mixtures with additional water. Transitory very low interfacial tensions against water were observed for mixtures along the aminosilicone-surfactant edge of the phase diagram. Inclusion of sufficient water in these mixtures produced clear compositions located in an isotropic region. It is believed that the isotropic region is an association complex, possibly inverse micellar, involving hydrogen bonding between water, ether oxygen atoms of the nonionic surfactant and amino groups of the aminosilicone polymer. Oil-surfactant-water compositions in this isotropic region result in ultra-low interfacial tensions against water that pass through a minimum value with time, are at least an order of magnitude lower (<0.0001 mN m −1) than without associated water, and occur in a shorter period of time. The interfacial tensions of isotropic compositions that contain sufficient surfactant to stabilize a microemulsion could not be measured but are believed to be even lower and reached more rapidly. Surprisingly, compositions in this isotropic region yield silicone-in-water microemulsions on instantaneous dilution toward the water corner of the phase diagram. Gradual dilution of compositions in the isotropic region with water failed to produce such microemulsions and instead yielded opaque two or more phase mixtures. Oil-in-water microemulsions were easily made by quickly shaking an isotropic mixture in water to achieve mixing. By this technique, it is believed that mixing to disperse the aminosilicone polymer in the dilution water occurs in the same time period when ultra-low interfacial tensions are present. (In contrast, gradual dilution with water slowly changed the mixture composition until it was out of the isotropic region and entered a two-phase region where an opaque emulsion of much larger particle size formed.) Microemulsions with aminosilicone oil concentrations of 5, 10, 20, 30 and 40% were produced from the same isotropic mixture with essentially no variation in the particle size produced. The microemulsions made by this technique appear to be kinetically stable, remaining unchanged in particle size for years. They may be further diluted with water without any change in particle size and can be used in formulations much as with standard emulsions.

Kinetics and instabilities in the extraction of Co(II) by sodium di-(2-ethylhexyl) phosphate at the water/toluene interface: I. Kinetics and mechanism

A toluenic solution of sodium di-(2-ethylhexyl) phosphate (NaD2EHP) was allowed to react with an aqueous solution of Co(II) in a nonagitated system. Two layers of NaD2EHP emulsions in water appeared: a dilute emulsion A and an opaque emulsion B located below the toluenic phase. Furthermore, spontaneous convective motions were observed. The kinetics of complexation was investigated by spectrophotometry. The influence of four factors was studied: the Co 2+ concentration C m, the NaD2EHP concentration C d, the inert anti-emulsifier (KBr) concentration C e, and the hydration degree I h of the surfactant. When C m was increased, the reaction rate w exhibited a maximum at C m = 15 moles m −3 and then a minimum at C m = 30 moles m −3. The whole dependence w( C m, C d, C e, I h) is explained by a double location of a superficial reaction with proper reaction orders of 1 relative to Co 2+ and 0 relative to NaD2EHP. The results show that, in the absence of forced convection, the rate w of the Co(II) extraction is the sum w 1 + w 2 where w 1 is the reaction rate at the surface of the droplets in layer B and w 2 represents the reaction rate at the macroscopic W/O interface. An increase in C m resulted in a strong reduction of the intensity E of the emulsification. Conversely, an increase in E led to an increase in the droplet area and therefore an increase in w 1, while w 2 was reduced via an increase in the resistance to the diffusion of Co 2+ through the aqueous interstices of emulsion B.

Stabilization of water/oil/water multiple emulsions by polymerization of the aqueous phases.

In order to improve the stability of w/o/w multiple emulsions which have isopropyl myristate as the non-aqueous 'oil' phase, either the internal aqueous phase of the multiple system or the secondary (outer or continuous) aqueous phase can be gelled. Production, by gamma-irradiation, or cross-linked polyacrylamide or poloxamer gels in the aqueous phases of the emulsions leads to systems which have a greater intrinsic stability than untreated multiple emulsions. If the internal aqueous phase is gelled this prevents coalescence. When the continuous outer phase is gelled an opaque emulsion is produced in which the disperse w/o droplets are held in a hydrophilic polymer network from which the droplets are released on contact with water.

Stable Emulsion Regions of Surfactant-Oil-Water and Surfactant-Oil-Water-Long Chain Alcohol Systems

A ternary diagram for nonionic surfactant-oil-water system was studied and the region of stable and strongly opaque emulsion (the region E1) was determined on the diagram. It was found that the E1 region existed only within the two-phase region consisting of a viscous isotropic phase and an oil phase, and that at least 10% surfactant was necessary to obtain this region.The quarternary system containing cetostearyl alcohol in addition to the ternary system was also examined. Addition of the alcohol produced a new stable region of strongly opaque emulsion (the region E2) besides E1. The appearance of the region E2 reduced the minimum surfactant concentration to obtain the stable and strongly opaque emulsion to about 2%. Similar effect was observed for behenyl alcohol of cosmetic grade, which is also a mixture of alcohols. However, pure alcohols of carbon numders from 12 to 16 lacked the ability to form the E2 region. Those of carbon numbers of 18 and 20 gave the E2 region but only above the surfactant concentration of 5%.

Pain is perspective.

PAIN IN PERSPECTIVE, 1975 B. RAYMOND FINK* Pain, one might have thought, should be a prime topic ofconversation between the intellectuals and the scientists, the people of the two cultures who, according to C. P. Snow, have almost ceased to communicate. Certainly pain seems a more propitious subject than the second law of thermodynamics, Snow's original proposal, or molecular biology, his later suggestion [I]. What could be more conducive to mutual respect than shared insights into our growing understanding of the mechanism of feeling in general, and pain in particular? True, one might question whether pain is ripe for such recognition when perhaps the most eminent Soviet psychologist of our time can write an entire work on neuropsychology [2] without ever mentioning it. On the other hand, the urgency of at least planning a dialogue is clear now that two distinguished books [3, 4] have surveyed the gamut of scientific and clinical comprehension of pain yet passed over in silence its cultural influence and religious significance. As to the last, the poverty of apologetics, recent and not so recent [5, 6, 7], is a standing reproach to the insularity of both cultures. The meagerness of the philosophy of pain is astonishing when one considers the vast artistic, intellectual, and physical activities surrounding the sensations of sight and hearing. Yet, one cannot doubt that pain is a fundamental element in our social fabric. From our first day each one of us is united in suffering, or the fear of suffering, with the mother who gave us birth. Whether regarded as an occasion for compassion, punishment, or vengeance or for endurance, prayer, or therapy, the infliction and assuaging of hurt are two of the dominant influences in "civilized" human thought and action and apparently have always been so. Today more than ever they make up two of the largest industries on the face of the planet. In an epoch of unprecedented ethical dilemmas flowing from un- *Department of Anesthesiology, the Anesthesia Research Center and the Center for Research in Oral Biology, University of Washington School of Medicine, Seattle, Washington 98195. Supported by grants DE 02600-08 and GM 15991 from the National Institutes of Health, U.S.P.H.S. I am indebted to Dr. Richard G. Black, coordinator of the pain clinic at the University of Washington, for much stimulating discussion. 278 I B. Raymond Fink · Pain in Perspective imagined technological advances, pain may yet confront humanity with a more pervasive moral quandary than any it has yet had to face. At a time when self-gratification by electrical stimulation of the brain is an accomplished fact, a daily existence rendered universally pain free by artificial means seems a promise (or menace) realizable in the not-sodistant future. Suppose, as may yet be, that it were within the gift of science to abolish pain—to abolish physical suffering without other perceptual cost permanently, once and for all, for every person, at that person's decision. What would you decide? The background for a responsible answer to that question includes a clear understanding of the biology and the social functions of pain. Much ofthe former has become readily accessible in The Puzzle ofPain by Ronald Melzack [3], an important milestone in the expository literature of the subject, and in the less comprehensive but equally luminous Pain Patients [4], Sternbach's sequel to his The Psychology ofPain of a few years ago. These books epitomize the modern scientific understanding and ignorance of pain. But there is another type ofunderstanding or interpretation, religious or cultural in nature, and most familiar perhaps in the Judeo-Christian belief that suffering is divinely ordained retribution for evil deed and thought. Considering how intimately it has permeated western thought, the slender measure of its literature in recent times is striking. Faced with a sparsity of contemporary theological apologia for pain [7], we are forced to advert to books from well-intentioned laity. In Pain and Religion, Brena [5] gamely attempts to bring the two worlds of religion and science together; but they have never appeared more totally immiscible than in this opaque emulsion of noble aspirations and clotted language. Brena, who was at one time director of...

Methods for the preparation of autoradiographs with coverslip cultures.

AUTORADIOGRAPHIC procedures are being increasingly used in all branches of cell biology. The routine methods are extremely useful with sections and air dried cell suspensions1–4, but the extension of these methods to coverslip cultures has often been unsatisfactory. The usual procedure for coverslip preparations involves cementing the coverslip cell side up on a slide in a drop of mounting medium (usually ‘Permount’) before covering with liquid emulsion or AR 10 stripping film5. This method often causes opaque emulsion patches in the space between coverslip and slide and the coverslip quite frequently floats off during rehydration. This communication describes a method which eliminates some of the problems encountered in autoradiography on coverslip cultures.

SKIAGRAPHIC STUDY OF THORAX, THORACIC WALL AND THORACIC VISCERA

The Roentgen-ray picture of the normal or abnormal thorax invariably shows certain opacities corresponding to the hilus of the lung. Latent tuberculosis is found in this same location, and it has been stated that tuberculosis always begins here and spreads through the lung in a peripheral direction. It is of prime importance, therefore, to ascertain if possible the cause of these opacities. An attempt was made to analyze the roentgenogram of the thorax by taking a cadaver and making a Roentgen-ray plate of the thorax intact; of the thorax with heart and lungs removed; of the posterior thoracic wall alone ; of the detached heart and lungs ; of the heart separate ; of the lungs freed from the heart and vessels, and finally of the lungs with the bronchi, artery, or vein injected with opaque emulsion of barium sulphate, or with citrated blood. The cadaver was that of a negress,