Solubilization capacity and structural transformations in nonionic microemulsions characterized by a large continuous isotropic region forming dilutable self-assembled nanodroplets contg. solubilized carbamazepine, were studied along diln. lines 73 and 82 (70 and 80% surfactant and 30 and 20% of oil phase, resp.). The prepns. 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 wt. ratio. The SC in the conc. (reversed micelles) was 15 times higher than its soly. in the oil. Transition of the W/O microemulsion to a bicontinuous phase and to O/W droplets were identified by elec. cond., viscosity, SAXS, and SD-NMR measurements. Once the system is dild. to 90% aq. phase, the SC is 10 and 16-fold higher, along diln. lines 73 and 82, resp., 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. [on SciFinder(R)]

A H2O-in-oil microemulsion was further dispersed in an aq. phase contg. Pluronic F127 as a steric stabilizer, to form a specific type of double emulsion termed emulsified microemulsion (EME). The inner microemulsion phase was made from glycerol-monooleate (GMO), R(+)-limonene, EtOH and glycerol. SAXS (small x-ray scattering), PGSE-NMR (pulse gradient spin echo-NMR), elec. cond., and cryo-TEM (cryogenic-TEM) imaging techniques were used to confirm the existence of inner W/O nano-droplets after 2nd emulsification step and upon EME aging. Spherical globules of EME without long-range internal order were obsd. by the SAXS measurements and the cryo-TEM images. The av. globule size of ∼200-300 nm remained intact for at least 6 mo. [on SciFinder(R)]

The present short review aims to summarize advanced nucleating agents for polypropylene (PP). Reviewing the relevant literature, we focused on powerful nucleators that are capable of significantly increasing the crystn. temp. of the polymer at very low working concns. and also serving as clarifying agents. The nucleation mechanism and efficiency of these compds. are discussed in detail. The nucleating agents were divided into groups according to their tendency to induce monoclinic ($\alpha$), hexagonal ($\beta$), or orthorhombic ($\gamma$) PP cell geometries. The major $\alpha$-nucleators and clarifiers are sorbitol-based compds. that speed-up the polymer crystn. due to gelation phenomena and induction of epitaxial crystn. by the metal salts of substituted arom. heterocyclic phosphate. Among $\beta$-nucleators, N,N'-dicyclohexyl-2,6-naphthalene dicarboxamide was found to be very efficient and its nucleation ability was highly concn. dependent. In addn., it was shown that nucleation efficiency of a nucleator can be significantly increased by a new dispersion method comprising its solubilization in a microemulsion. Moreover, the nucleator (HPN-68) increased the $\gamma$-modification present in the polymer. [on SciFinder(R)]

In the present study we demonstrate that large quantities of cyclosporin A and three dermal penetration enhancers (phosphatidylcholine, ethanol, or Labrasol) can be solubilized into reverse hexagonal (HII) liq. cryst. structures composed of monoolein, tricaprylin, and water. The microstructural characteristics of these complex multi-component systems were elucidated by rheol., SAXS, and DSC measurements. Addn. of up to 20 wt% phosphatidylcholine improved significantly the elastic properties of the systems (lower values of tan $δ$ ) and increased the thermal stability of the mesophases enabling us to solubilize up to 6 wt% cyclosporin A and two other enhancers (Labrasol and ethanol) to obtain stable mesophases at physiol. temp. Rheol. measurements revealed that solubilization of cyclosporin A alone has a destabilizing effect on the reverse hexagonal phases: it caused a deterioration in the elastic properties of the systems, leading to more liq.-like behavior and resulting in very short relaxation times (0.04-0.1 s). Labrasol, solubilized at high concns. (up to 12 wt%) into the liq. crystals, also demonstrated a destabilizing effect on the HII structure: the decreasing elasticity of the system was attributed to Labrasol's presumed locus at the interface and its ability to bind water, as shown by DSC measurements. Ethanol had a destabilizing effect similar to that of Labrasol, yet the effect appeared to be more pronounced, probably due to its higher water-binding capability. [on SciFinder(R)]

It is well documented that phytosterols inhibit the uptake of exogenic cholesterol and do not interfere with cholesterol synthesis or cause side effects. The mechanism by which phytosterols interfere with cholesterol absorption is not completely clear and there are at least three hypotheses for their beneficial activity. Among these is that of competitive solubilization of phytosterols and cholesterol in dietary mixed micelles. In the present study we investigated the competitive solubilization of phytosterols (approx. 50% $\beta$-sitosterol) and cholesterol in a nonionic microemulsion system constructed as a model for the dietary mixed micelles. We studied the effect of the competitive solubilization of cholesterol and phytosterols on the structural transformations and phys. properties of the microemulsion and evaluated the locus of the solubilizates within the nanodroplets of each sterol sep. and when they are loaded together at different wt. ratios along one diln. line. Our results show that chem. and structural differences between cholesterol and phytosterols significantly influence the solubilization capacity of the nonionic microemulsion. Cholesterol, being more amphiphilic, is solubilized more efficiently at the W/O microemulsion interface, while in the O/W microemulsion phytosterols are dissolved somewhat more efficiently in the droplet core. [on SciFinder(R)]

A review discusses macroemulsions, miniemulsions, microemulsions, and double emulsions and their behavior. [on SciFinder(R)],3rd Edition.

The present study evaluates the effect of a solubilized model drug, diclofenac sodium salt (diclofenac), in our unique new U-type microemulsion system embedded with phosphatidylcholine (PC) in terms of microstructure transformations, phys. properties of the system (viscosity, elec. cond.), droplet sizes and shapes, and nucleation and growth of the droplets. The phys. properties are correlated to the permeability of diclofenac through Caco-2 monolayer cells. The major findings reported are: (1) systems that are rich in surfactant and contain minimal oil phase form a microemulsion that enables high solubilization of diclofenac (20% diclofenac in the oil and surfactant conc. can be fully dild. with water); (2) PC presence at the interface does not affect the size of the O/W droplets, while the presence of diclofenac at the interface decreases the O/W droplet size by an av. of 50%; (3) diclofenac seems to increase incorporation of PC into the W/O interface; (4) diclofenac affects the phys. properties of the microemulsion increasing the viscosity of the W/O microemulsion system and completely changing the cond. profile of the system upon water diln.; (5) cryo-TEM images indicate that above 70% water the droplets are spherical; (6) diclofenac permeability through Caco-2 monolayer cells increases when PC is embedded into the interface. [on SciFinder(R)]

A review on the use of microemulsions as drug and nutraceutical delivery vehicles. Some of the major concepts related to the formation of microemulsions in general, and in particular, the formation of a new U-type microemulsion that is fully dilutable and of high solubilization capacity are summarized. Applications of microemulsions as delivery systems for drugs and nutraceuticals are discussed, with emphasis on recent progress in the U-type microemulsions as delivery systems of poorly water-sol. drugs and nutraceuticals. [on SciFinder(R)]

The present invention relates to pharmaceutical compns. in the form of microemulsions comprising carbamazepine and their enhanced permeability and extended release properties. The microemulsion compn. may be an oil-based formulation or an oil/aq. phase mixed formulation. Thus, a microemulsion conc. contg. 5% of solubilized carbamazepine was prepd. by mixing 28.8% of a D-limonene/ethanol (1:1) with 67.3% of Tween 60 to form a 7:3 conc. In the next step 3.85% of carbamazepine were solubilized in the conc. to give the slightly yellow colored, clear and stable compn. This conc. may be totally dild. by an aq. phase with no phase sepn. The conc. may be taken orally where its diln. in the stomach should not form any disintegration of the conc. Each 20.8 g of the compn. contain 800 mg carbamazepine. In the compn. the carbamazepine bioavailability is much higher, hence the consumed dose required for effective action will be much lower and should be detd. Except for the microemulsion conc. form, the drug could be consumed at a dild., ready microemulsion. [on SciFinder(R)]
Patent devoted to the solubilization ob carbamazepine into interfaces of microdroplets

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 H2O soly. (\textless5 $μ$g/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 dissoln. was very small and its dispersion in H2O was impossible. In recent studies, the authors learned to construct U-type phase diagrams and to formulate reverse microemulsions (oil-based concs.) that are progressively and fully dilutable with aq. phase. The authors solubilized clxb in nanostructures of reverse micelles of U-type nonionic microemulsions that consisted of R(+)-limonene, alc., 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 aq. phase. The clxb solubilized microemulsions are fully dild. with aq. phase without phase sepn. The solubilization capacity decreases as the H2O content increases. Elec. cond., viscosity, and self-diffusion (SD) coeffs. of the microemulsion components were measured along a suitable H2O diln. line. The 3 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% aq. phase, resp.). From the SD coeffs., 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 H2O content as in the empty (i.e., without drug) system. From the viscosity profiles, the drug affects the structure of the bicontinuous phase as reflected in the H2O content at which the oil-continuous network is destroyed and full inversion occurs (50 vs. 55% in the drug-loaded system). Upon further diln. the drug remains solubilized at the interface and is oriented with its hydrophilic part facing the H2O, and is strongly affects the inversion to O/W droplets. From Small Angle x-ray Scattering (SAXS) measurements the drug effects the structure of microemulsion droplets and forms ill-defined structures, probably less spherical. Yet, the overall droplet sizes at the high dilns. did not change very much. [on SciFinder(R)]

A review. Microemulsions are clear, stable, isotropic mixts. of oil, water, and surfactant, frequently in combination with a cosurfactant. Microemulsions were intensively studied during the last decades by many scientists and technologists because of their great potential in many food and pharmaceutical applications. The use of microemulsions is advantageous not only due to the facile and low cost prepn., but also because of the improved bioavailability. The increased absorption of drugs in topical applications is attributed to enhancement of penetration through the skin by the carrier. Satd. and unsatd. fatty acids serving as an oil phase are frequently used as penetration enhancers. The most popular enhancer is oleic acid. Other permeation enhancers commonly used in transdermal formulations are iso-Pr myristate, iso-Pr palmitate, triacetin, isostearylic isostearate, R(+)-limonene, and medium chain triglycerides. The most popular among the enhancing permeability surfactants are phospholipids that were shown to enhance drug permeation in a different mode. L-$\alpha$-phosphatidylcholine from egg yolk, L-$\alpha$-phosphatidylcholine 60%, from soybean and dioleylphosphatidyl ethanolamine which are in a fluid state may diffuse into the stratum corneum and enhance dermal and transdermal drug penetration, while distearoylphosphatidyl choline which is in a gel-state has no such capability. Other very commonly used surfactants are Tween 20, Tween 80, Span 20, Azone, Plurol Isostearique, and Plurol Oleique. As cosurfactants commonly serve short-chain alkanols such as ethanol and propylene glycol. Long-chain alcs., esp. 1-butanol, are known for their enhancing activity as well. Decanol was found to be an optimum enhancer among other satd. fatty alcs. that were examd. (from octanol to myristyl alc.). Many enhancers are concn.-dependent; therefore, optimal concn. for effective promotion should be detd. The delivery rate is dependent on the type of the drug, the structure and ingredients of the carrier, and on the character of the membrane in use. Each formulation should be examd. very carefully, because every membrane alters the mechanism of penetration and can turn an enhancer to a retarder. Various potential mechanisms to enhance drug penetration through the skin include directly affecting the skin and modifying the formulation so the partition, diffusion, or soly. is altered. The combination of several enhancement techniques such as the use of iontophoresis with fatty acids leads to synergetic drug penetration and to decrease in skin toxicity. Selected studies of various microemulsions contg. certain drugs including retinoic acid, 5-fluorouracil, triptolide, ascorbic acid, diclofenac, lidocaine, and prilocaine hydrochloride in transdermal formulations are presented in this review. In conclusion, microemulsions were found as an effective vehicle of the solubilization of certain drugs and as protecting medium for the entrapped of drugs from degrdn., hydrolysis, and oxidn. It can also provide prolonged release of the drug and prevent irritation despite the toxicity of the drug. Yet, in spite of all the advantages the present formulations lack several key important characteristics such as cosmetic-permitted surfactants, free diln. in water capabilities, stability in the digestive tracts and sufficient solubilization capacity. [on SciFinder(R)]

This is the first of a two-part study focusing on a novel dispersion method which enables increasing the crystallization rate of polypropylene (PP) through the incorporation of nucleating agent HPN-68 into the molten polymer using a microemulsion as a nanovehicle. The cycle time for processing the PP is significantly reduced and thus the effectiveness of its production is increased. Our concept is based on creating an advantage in dispersion capability of the nucleator that is dissolved in a nanoreactor vehicle in comparison with its conventional introduction as a crystalline powder. The microemulsions were introduced to the target PP using a mixer. By the end of the mixing, when the water phase had evaporated, only the nucleator and the surfactant remained in the matrix. The microemulsion components that solubilized the HPN-68 were mineral oil, alcohol, surfactant, and water. DSC results showed a 24% improvement in nucleation efficiency of PP by this method. WAXS results showed that HPN-68 is a gamma-nucleator. It causes polymorphism by significantly raising the gamma-phase concentration in the PP. SEM results showed a four-fold decrease in the PP spherulite size due to the improved dispersion of HPN-68 within the matrix via microemulsion compared to conventional nucleator incorporation. (c) 2006 Elsevier Inc. All rights reserved.

A review. Cholesterol is an essential lipid for mammalian life, but a high cholesterol level can almost guarantee the eventual onset of vascular diseases and, in some cases, can lead to death. It has been shown that there is a direct connection between high cholesterol levels and vascular diseases. Some methods for lowering the serum cholesterol level, thereby preventing the development of these diseases, have been developed and those include drugs and food additives. Since both drugs and food additives act to inhibit the uptake of cholesterol, understanding the sterol absorption process is the key to understanding exactly how drugs and food additives reduce serum cholesterol levels. The major drawback of using anti-cholesterol drugs is related to their side effects, and therefore, natural food additives called plant sterols (phytosterols) have been developed as an attractive alternative. Phytosterols are sterols that are synthesized only in plants and that are structurally similar to cholesterol but with the inclusion of an extra hydrophobic carbon chain at the C-24 position. Phytosterols and their esters reduce cholesterol level in the blood in spite of the fact that they are poorly absorbed into the blood stream. The mechanism by which phytosterols/phytosterol esters interfere with cholesterol absorption is not completely clear, but based on the present understanding, three distinct features have been recognized: (1) physico-chem. effects (e.g. competitive solubilization and co-crystn.); (2) effects at the absorption site (e.g. hydrolysis by lipases and esterases); (3) effects on intra-cellular trafficking of sterols. Due to phytosterols' poor solubilization in oil and water, they must be taken in high doses to achieve a redn. in cholesterol level. One of the goals of the food and pharmaceutical industries, therefore, is to develop products that effectuate the same decrease in cholesterol level but in smaller sterol doses achieved by increasing sterol bioavailability. The first line of products to meet the increased bioavailability criterion was the oil-sol. esterified phytosterols combined with fatty acids, which exhibit soly. in oil 10 times higher than that of pure phytosterols. The three primary methods of phytosterol inclusion in food are suspension, pptn. and microemulsion. [on SciFinder(R)]

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 diln. lines (50:50 and 80:20% surfactant mixt./oil phase). From the water thermal behavior we learned that three structural regions can be identified along the water diln. lines. The thermal transition points coincide with the structural phase transition of the microemulsions as measured by other methods (elec. cond. and SD-NMR measurements). The structural transitions were detected at 20 and 45% of water along diln. line 55, where along diln. line 82 it occurs at 40 and 50% of water. The microemulsions along diln. line 82 seem to have more compact surfactant packing film, thus the film has stronger resistance to transformation upon diln., resulting in a smaller bicontinuous region than the one formed at diln. line 55. The difference in phase transition point can be used for triggering the release of future solubilizate. [on SciFinder(R)]