Evidence on the role of phosphatidylcholine (PC) as a membrane permeability enhancer was the driving force in forming new liq. nanosized (modified microemulsions) oral delivery system contg. PC mols. We have demonstrated the feasibility of constructing phase diagrams with a large isotropic regions capable of being fully dild. with water. The microemulsions were stabilized with mixts. composed of PC and nonionic surfactant (polyoxyethylene-40 hydrogenated castor oil, HECO40) and short-chain org. acid as cosurfactant/cosolvent. When propionic acid served as the cosurfactant/cosolvent, the isotropic region was at its max. (ca. 72% of the total phase diagram area). The presence of a blend of PC and HECO40 seems to have synergistic effects, forming an isotropic region comprising 72% of the area of the phase diagram, in comparison to 20 and 50% in systems stabilized by PC and HECO40, alone, resp. The role of the PC mols. in the formation of those microemulsions is demonstrated by comparing three soy lecithins. Lecithin with a high PC content forms larger isotropic regions with more "free diln." lines. Several nonionic surfactants were investigated, yet only HECO40 seems to have a packing parameter suitable for the formation of large isotropic U-type systems. [on SciFinder(R)]
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.
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)]
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)]
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
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)]
