it � oil v � fig a hypothetical pseudoternary phase diagram of an oilsurfactantwater system with emphasis on microemulsion and emulsion phases within the phase diagram, existence fields are shown where micelles, reverse micelles or waterinoil wo microemulsions and oilinwater microemulsions are formed along with the bicontinuous microemulsions at very low surfactant concentrations two phase systems are observed taken from ref fractions, microemulsions are generally considered to be a dispersion of either oil or water droplets stabilized by an interfacial film of surfactant and where appropriate, cosurfactant these droplet structures are probably the most commonly encountered type of microemulsion zantac for infants microstructure it is worth noting that both an emulsion and a nanoemulsion can only occur in the form of a droplet, either as an oilinwater or waterinoil droplet at intermediate oil and water compositions, it is obviously not possible for the microstructure to be composed of droplets of one phase dispersed in the other in these cases, it is thought that a bicontinuous structure exists, in which the water and oil domains are separated by a regular or topologically chaotic continuous amphiphilerich interfacial layer a bicontinuous microemulsion is often the intermediate microstructure between an oilinwater and a waterinoil microemulsion, although a zantac for infants number of other microstructures such as cylinders and wormlike microemulsions have been reported to exist in terms of its microstructure, a microemulsion is therefore a very complex system, and in instances where a microemulsion exists over a wide range of compositions, several different types of microstructure may be present it is also important to remember that whatever the microstructure, a microemulsion is a dynamic system in which the interface is continuously and spontaneously fluctuating for this reason, microemulsions stabilized by polymeric surfactants may be the most long lived microemulsions, swollen micelles, micelles there is much debate in the literature as to zantac for infants what exactly differentiates a microemulsion from a micelle at low volume fractions of disperse phase some investigators have perceived a difference between microemulsions and micellar systems containing solubilized oil or water, and have used the terms swollen micellar solutions or solubilized micellar solutions to describe such systems these investigators argue that the term microemulsion should be restricted to systems in which the droplets are of large enough size such that the physical properties of the dispersed oil or water phase are indistinguishable from those of the corresponding oil or water phase, thereby theoretically making it possible to distinguish between oilinwater or zantac for infants waterinoil microemulsions and micellar solutions containing small amounts of solubilized oil water however, in most cases, the transformation between micelles progressively swollen with oil water and a microemulsion containing an isotropic core of oil water appears to be gradual with no obvious transition point as a consequence, there is no simple method available for determining the oil water content at which the core of the swollen micelle becomes identical to that of a bulk phase many researchers therefore use the term microemulsion to include swollen micelles, but not micelles containing no oil or water in biotechno logical applications, waterinoil microemulsions are zantac for infants frequently known as reverse micelles and or even as nonaqueous media microemulsions and cosolvent systems the above broad definition does not require a microemulsion to contain any microstructure in other words, it includes systems that are cosolvents, ie systems in which the constituent components are molecularly dispersed most researchers in the field agree, however, that for a microemulsion to be formed, it is important that the system contains some definite microstructure in other words, there is a definite boundary between the oil and water phases, and at which the amphiphilic molecules are located and that a cosolvent is not a type zantac for infants of microemulsion the only way to distinguish a microemulsion from a cosolvent unambiguously is to perform either a scattering study light, xrays or neutrons or pfgnmr measurements regions of cosolvent formation generally appear at low concentrations of oil or water microemulsions as drug delivery systems it is clear from its description that microemulsions possess a number of properties that make their use as drug delivery vehicles particularly attractive indeed, microemulsions were first studied with the view of using them as potential vehicles for poorlywater soluble drugs, in the mid s by elworthy and attwood however, it was not until the mid zantac for infants to late s that they were widely investigated as drug delivery systems this interest being largely the result of the arrival on the market of the cyclosporin a microemulsion preconcentrate, neoral among the physical properties that make microemulsions attractive as drug delivery vehicle is their transparent nature, which means that the product is not only aesthetically pleasing, but allows easy visualization of any contamination the small size of the domains present means that a microemulsion can be sterilized by terminal filtration furthermore, depending on the composition of the microemulsion, it may be possible to heat sterilize the microemulsions since oil inwater zantac for infants microemulsions are able to incorporate lipophilic substances, they can be used to facilitate the administration of waterinsoluble drugs significantly, the small droplet size provides a large interfacial area for rapid drug release, and so the drug should exhibit an enhanced bioavailability, enabling a reduction in dose, more consistent temporal profiles of drug absorption, and the protection of drugs from the hostile environment of the body in addition to increasing the rate of drug release, microemulsions can also be used as a reservoir and actually slow the release of drug and prolong its effect, thereby avoiding high concentrations in the blood whether zantac for infants a drug is rapidly or slowly released from a microemulsion depends very much on the affinity of the drug for the microemulsion since microemulsions contain surfactants cosurfactants and other excipients, they may serve to increase the membrane penetration of drug a number of reviews have been presented, describing the pharmaceutical use of microemulsions since the last major review in the area was writen in , the present review will mainly deal with developments henceforth, although important work prior to this will be discussed when appropriate selfemulsifying drug delivery systems sedds before discussing how microemulsions are being exploited in drug delivery, it is zantac for infants worth making one more distinction, namely the difference between a self emulsifying drug delivery system sedds and a microemulsion a sedds is a mixture of oils, and surfactants, ideally isotropic, sometimes containing cosolvents, which when introduced into aqueous phase under gentle agitation, spontaneously emulsifies to produce a fine oilinwater dispersion typically, the size of the droplets produced by dilution of a sedds is in the range of and nm, while, upon dispersal in water, a smedds formulation a subgroup of the sedds forms a transparent microemulsion with particle sizes nm asmeeds is also known as a premicroemulsion concentrate it is worth zantac for infants noticing that this method of producing a fine oilinwater emulsion using a smeeds is identical to the low energy emulsification method for producing oilin water nanoemulsions it is therefore likely that a diluted smedds and nanoemulsion are identically the same the technique of lowenergy or selfemulsification has been commercially exploited for many years in the agrochemical industry, in the form of emulsifiable concentrates of lipophilic herbicides and pesticides however, it has only recently been introduced in the pharmaceutical industry as a tool to improve the delivery of lipophilic drugs by incorporating the drug into a smedds formulation which is then filled zantac for infants into capsules once the capsule has been swallowed and its contents come into contact with the gi fluid, the drug containing microemulsion should be spontaneously formed once the drug containing microemulsion is formed, there should be little difference between the fate of the drug thus administered and the same drug administered in a preformulated microemulsion, although the droplets formed from the smedds tend to be of a larger size one advantage of administering a drug in a smeeds as opposed to a preformulated microemulsion, is its relatively small volume which can be incorporated into soft or hard gelatin capsules, convenient for zantac for infants oral delivery to date, there has been a good amount of commercial success for the first self microemulsifying drug delivery systems smedds on the market, namely neoral cyclosporin a in addition, the recent commercialization of two selfemulsifying formulations, namely norvir ritonavir and fortovase saquinavir, has undoubtedly increased the interest in sedds and other emulsionbased delivery systems to improve the delivery of a range of drugs of varying physicochemical properties however, there are a number of reasons why smedds are not in greater widespread use, but the main reason is probably the stability of the diluted sedds, which is in fact a zantac for infants thermodynamically unstable emulsion although it may exhibit some limited kinetic or meta stability it should be noted however that as a sedds is either diluted just prior to administration or else in the body, the required droplet stability is less than hrs ie the transit time of materials down the small intestine although most studies of seeds have utilized isotropic liquids, the earliest reports of these selfemulsifying systems using pharmaceutical materials are in fact related to pastes based on waxy polyoxyethylene zalkyl ethers in the context of drug delivery via selfemulsifying systems, isotropic liquids are generally preferred to waxy pastes because zantac for infants if one or more excipients crystallizes on cooling to form a waxy mixture, it is very difficult to determine the morphology of the materials despite this, there is currently a general move towards formulating semisolid sedds for example, attempts have been made to transform sedds into solid dosage forms by addition of large amounts of solidifying excipients such as adsorbents and polymers, unfortunately, as the ratio of sedds to solidifying excipients required for this approach is very high, this leads to problems in formulating drugs having limited solubility in the oil phase recent attempts have been made to reduce the amount zantac for infants of solidifying excipients by gelling the sedds with colloidal silicon dioxide khoo et al have recently reported the preparation of a halofantrinecontaining lipidbased solid selfemulsifying system using either vitamin e tpgs or a blend of gelucire vitamin e tpgs as the base upon dispersal, these systems produced dispersions that the authors described as microemulsions studies in fasted dogs showed that these solid dispersions exhibited a five to sevenfold improvement in absolute oral bioavailability, when compared with the commercially available tablet formulation in a different approach, nazzal et alp have determined the potential of a reversibly induced recrystallized semisolid selfnanoemulsifying drug delivery zantac for infants system, based on a eutectic interaction between the drug and the carrying agent, as an alternative to a conventional sedds in these eutecticbased selfnanoemulsified systems, the melting point depression method allows the oil phase containing the drug itself to melt at body temperature from its semisolid consistency, and disperse to form emulsion droplets in the nanometer size range emulsion systems based on a eutectic mixture of lidocaineprilocaine, and lidocainementhol have been used in the preparation of topical formulations however, little is known of the use of eutectic mixtures for the preparation of selfmicro emulsified formulations related systems there are a number zantac for infants of other putative delivery systems that are closely related to, or are prepared from, a microemulsion these systems include a variety of gel formulations including microemulsionbased gels, ringing gels, microemulsion gels and double microemulsions microemulsion gels oilinwater microemulsions can be readily gelled or thickened by the addition of a noninteracting, watersoluble polymer such as polyhema, carbopol or carrageenan to form clear microemulsion gels in these cases, it is the external aqueous phase that is gelled, while the microemulsion droplets are unperturbed the structure of the resulting microemulsion gel is quite different, if it is prepared using an interacting polymer, such as zantac for infants stearatepolyethylene oxidestearate in this instance, the hydrophilic midblock of the polymer is located in the continuous aqueous phase, while the hydrophobic end blocks are dissolved in the oil droplets, thereby connecting the various microemulsion droplets and resulting in the formation of a transient gel network clear, microemulsion gels are also sometimes obtained at surfactant andor oil concentrations just outside the oil inwater microemulsion region sometimes, the resultant gel rings or vibrates when tapped the ringing is due to the resonance of shear modes within the gel body neither of these microemulsion gels, which are water continuous, are true microemulsions, which are zantac for infants fluid by definition clear gels can also be formed in oil continuous systems for example, a gel can be formed when water is added to reverse micellar solutions of lecithininoil, here, the water causes the wormlike lecithin reverse micelles to intertwine and form a gel in addition, gels, widely known as microemulsionbased gels, can be formed from waterinoil microemulsions stabilized predominately by the di chain surfactant sodium bis ethylhexyl sulfosuccinate aot, when gelatin, the natural amphiphilic polymer is added, microemulsionbased gels have now been prepared in systems in which a large amount of the aot has been replaced by nonionic surfactant zantac for infants or more recently, using in place of aot, the single chain surfactant, cetyltrimethylammonium bromide in combination with pentanol in these gels, the gelatin is thought to form watercontinuous channels between the microemulsiondroplets these microemulsionbased gels are very unusual in that, although they are oil continuous, they are electrically conducting in addition, the continuous oil behaves as if it were still a fluid, even though placing a gel in a solution of the oil does not dissolve it all of these microemulsion gels have potential, or are being explored for use as drug delivery systems of particular interest is the fact that zantac for infants the gels possess the properties of being transparent, infinitely stable and readily prepared using only the mildest of mixing in addition the wide range of microemulsion gels available means that it is possible to select the gel of the required consistency for application to large areas of skin, the nasal membrane, vaginal and buccal membranes and for permeation enhancement microemulsionbased gels have been explored as vehicles for the iontophorectic delivery of drugs double or multiple microemulsions double or multiple emulsions have attracted much interest as potential drug delivery vehicles for example, adding a watersoluble drug into the internal aqueous phase of zantac for infants a waterinoilinwater emulsion may allow the sustained release of the watersoluble drug a double microemulsion should offer similar advantages over the rate of drug release of entrapped solutes double emulsions are notoriously difficult to formulate due to the requirement to have one surfactant or mixture of surfactants to stabilize the first internal emulsion and a second surfactant or mixture of surfactants of quite different physicochemical properties to stabilize the second emulsion although a few papers have detailed the production of nanoparticles from systems they described as double microemulsions, the term double microemulsion in this context is very misleading, as it refers zantac for infants to the mixing of two waterinoil microemulsions of comparable composition, but containing different solute in the aqueous phase there are however two papers which describe the preparation of double oil inwaterinoil microemulsions in the first, castro et al, report spectroscopic studies of nifedipine in brij based oilwateroil multiple microemulsions in the second, carli et al, detail the preparation of an oilinwaterinoil microemulsion from an oily phase of either polyglycolized glycerides or a mixture of mono, di and triglycerides, which is microemulsified using a mixture of water and surfactant soy lecithin and tween the resultant �w microemulsion is subsequently re dispersed in zantac for infants an oily phase to produce the double owo microemulsion processed microemulsion formulations solid state or dry emulsions in practical terms, a solid dosage form is preferable to a liquid dosage form in respect of convenience, ease of handling and accurate dosing consequently, a number of researchers have attempted to develop powdered, redispersible emulsionderived formulations, known as solid state or dry emulsions such solidstate emulsions can be used to modulate the release rates of emulsified compound dry emulsions have been variously prepared by removing water from an oilinwater emulsion, using watersoluble or insoluble solid carriers or indeed a mixture of both watersoluble zantac for infants and waterinsoluble carriers, by rotary evaporation, lyophilization, or spray drying attempts have also been recently made to prepare dry microemulsions using similar methodology for example, moreno et al have lyophilized an amphotericin bcontaining lecithinbased oilinwater microemulsion in the presence of wt mannitol the lyophilized product was an oily cake from which the microemulsion could be easily reconstituted over several months the rationale for developing the waterfree formulation was to avoid the hydrolysis of lecithin, which occurs upon its dispersal in water, thereby preventing any deterioration of the formulation upon storage overall, the lyophilized lecithin based oilinwater microemulsions appear to be valuable zantac for infants systems for the delivery of amphotericin b, with regard to ease and lowcost of manufacturing and their stability and safety, compared with other formulations already in the market in a recent paper, carli et al reported an alternative approach to prepare a dry formulation known as a nanoemulsified composite of the coenzyme q, ubidecarenone this composite is prepared by incorporating the ubidecarenone into the inner phase of the double microemulsion, which is then deposited onto a solid microporous carrier such as crosslinked polyvinylpyrrolidone among the advantages offered by this approach are good processing and storage properties, easy redispersibility in water, high zantac for infants bioavailability and maintenance of the sub micron size of the released droplets kim et al, have prepared entriccoated solid state premicroemulsion concentrates by first preparing a premicroemulsion concentrate containing wt of the drug cyclosporin a, wt of a medium chain triglyceride, wt of surfactant and wt of cosurfactant the premicroemulsion concentrates were then entericcoated as films using polymers, such as sodium alginate, eudragit l and cellulose acetate phthalate, and the resulting films were pulverized to produce powdered, dry, enteric coated premicroemulsion concentrates using this approach, the authors successfully prepared a onceaday oral dose form of cyclosporin a formulation microemulsions are far zantac for infants more difficult to formulate than emulsions because their formation is a highly specific process involving spontaneous interactions among their constituent molecules in addition, in a number of cases, effects due to the order of the mixing of the component molecules have been observed since no adequate theory currently exists to predict from which molecules microemulsions can be formed, mainly because of the requirement to determine a number of unknown parameters, microemulsion formulations are generally developed empirically, although some useful practical guidance as to the choice of the constituent components can be found in the literature a recognized and classical approach to zantac for infants microemulsion formulation is to undertake a systematic study of the phase behavior of the systems understudying utilizing of phase diagrams a major drawback of this approach is the considerable time it takes to develop the phase diagram, especially considering the combination of possible oil, surfactant and cosurfactant, and the fact that time may be necessary for a system to equilibrate heat and sonication are therefore often used, particularly with systems containing nonionic surfactants, to speed up the formation process while there are now commercially available automated systems to prepare phase diagrams, the chief drawback of these systems is their cost a zantac for infants number of attempts have been recently made to use modeling to predict microemulsion formation, thereby aiding in the formulation of microemulsions a range of modeling techniques have been used including artificial neural networks genetic algorithms, and a combination of data mining, computeraided molecular modeling, descriptor calculation and multiple linear regression techniques, unfortunately, however, all of these techniques require a considerable amount of work prior to prediction, thereby restricting their potential usefulness furthermore, the amount of work required for the predictions increases as the number of components of the microemulsion increase microemulsions formulated from five components ie oil, water, surfactant, cosurfactant, electrolyte zantac for infants and drug are not uncommon in pharmaceutical use to the authors knowledge, to date, no work has been performed predicting how much drug can be incorporated into a microemulsion and whether the presence of drug has any effect on microemulsion phase behavior this is an important ommi sion as microemulsions cannot be considered to be inert, since the presence of drug in some instances greatly influences phase behavior see for example ref surfactants and cosurfactants the selection of components for the preparation of microemulsions suitable for pharmaceutical use involves a consideration of their toxicity, and if the systems are to be zantac for infants used topically, their irritancy and sensitizing properties as well there are a number of surfactant and cosurfactants that are considered acceptable for use as excipients in pharmaceutical formulation strickley has recently reviewed those surfactants and cosurfactants currently used in commercially available oral and intravenous formulations in the general scientific literature, by far the most widely used surfactant to prepare a microemulsion is the double chain, ionic surfactant, sodium bis ethylhexyl sulfosuccinate aot, although a large number of studies have used the single chain, nonionic surfactants of the type qej, where i is the number of carbons in the alkyl chain, c, zantac for infants and j is the number of ethylene oxide units in the polyoxyethylene chain, e both aot and the qej surfactants possess the important advantage of being able to form microemulsions in the absence of a cosurfactant unlike most other types of surfactant such as the widely studied single chain, ionic surfactant, sodium dodecyl sulphate sds, which will only form microemulsions in the presence of an alcohol cosurfactant neither aot nor sds would be considered to be apprpropriate for the preparation of pharmaceutically acceptable microemulsions, even though they are listed in the pharmaceutical excipient handbook, rowe et alli as a general rule, zantac for infants nonionic and zwitterionic surfactants tend to be less toxic than ionic surfactants and are therefore more widely used as pharmaceutical excipients assuming that the surfactants do not degrade into toxic materials, surfactants that posses biodegradablechemically unstable linkers tend to exhibit less chronic toxicity than those that are chemically stable for example, as a group, the polyoxyethylene �acyl surfactants exhibit ten times less chronic toxicity than their halkyl counterparts, mainly due to their quicker degradation time of days as opposed to weeks when it comes to comparing acute toxicity, the two groups of surfactants exhibit comparable toxicity perhaps the most widely used zantac for infants nonionic surfactants in pharmaceutical formulations are the polyoxyethylene sorbitan �acyl esters, ie the tweens and in particular, tween and tween , both of which are used parenterally and orally in addition, polyoxyethylene derivatives of the triglyceride, castor oil have acceptability for intravenous administration other pharmaceutically acceptable surfactants are the polyoxyethylene nalkyl ethers and nacyl esters, although both these groups of surfactant tend to be restricted for topical use other nonionic surfactants that are currently attracting much pharmaceutical interest, although they do not yet have acceptability, are the polyglycerol �acyl esters, the �alkyl amine noxides and the �alkyl polyglycosides or sugar surfactants the zantac for infants �alkyl polyglycosides have attracted much pharmaceutical interest, not because of their excellent biodegrad ability, but because they can be manufactured from renewable resources all of the aforementioned surfactants have been used to prepare microemulsions, generally as sole surfactant, the only exception being the �alkyl polyglycosides, which tend to require the presence of a cosurfactant pluronics or poloxamers of the type polyethylene oxidepolypropylene oxidepolyethylene oxide peoppopeo are another class of pharmaceutically attractive surfactant interestingly, most reports detailing the use of polymeric surfactants to stabilize a microemulsion describe the preparation of waterinoil, generally in conjunction with a second surfactant, siebenbrodt and keipert have zantac for infants reported the formation of a triacetininwater microemulsion using pluronic l as sole surfactant lettow et al have used pluronic pi as sole surfactant to prepare oilinwater microemulsions, incorporating a oilp weight ratio of either trimethylbenzene or ,dichlorobenzene finally, the pharmaceutically acceptable zwitterionic lecithin has been extensively used as a surfactant, however, with very few exceptions, it is not possible to prepare a microemulsion using lecithin as sole surfactant generally, lecithin is combined with another surfactant such as tween , or a cosurfactant such as ethanol, when formulating microemulsions although ethanol is considered to be pharmaceutically acceptable, typical cosurfactants such as propanol and zantac for infants butanol are not in addition to toxicity issues, the use of such cosurfactants, which may possess partial oil and watersolubility, can lead to problems with the dilutability of the microemulsion this is a particular issue if the microemulsion is to be administered orally or parenterally consequently, a number of researchers have explored the use of a second surfactant as cosurfactant when formulating a microemulsion microemulsions thus prepared tend to be very stable against dilution, as the cosurfactant generally has little solubility in either the oil or aqueous phase alternately pharmaceutically acceptable, short chain mono and diglycerides have been used in place zantac for infants of a short chain alcohol to successfully prepare microemulsions in a number of instances, short chain fatty acids such as sodium caprylate have been used as cosurfactants, primarily for the formation of microemulsions for oral delivery sodium caprylate is known to enhance absorption of drugs across the gastrointestinal tract a number of researchers have also used cosolvents such as the polyhydric alcohols, sorbitol, glycerol and propylene glycol to aid microemulsion formation in a number of instances, these materials have been described as cosurfactants, which quite clearly do not sit in the interfacial surfactant monolayer rather, they tend to exert their effect zantac for infants by altering the solvent properties of the polar phase oils most reports in the chemical literature detail the preparation of microemulsions using aromatic oils such as benzene and short chain alkanes such as hexane pharmaceutical oils, unlike those used in the chemical and agrochemical industries, tend to be large in terms of molecular weight and therefore volume, and are relatively polar both of these properties tend to work against the oil when it comes to formulating it in a microemulsion, as it is well established that smaller molecular volume oils are easier to solubilize and are solubilized to a greater extent zantac for infants than larger oils although there are reports that in some systems, particularly those containing surfactants with long, unsaturated hydrophobes such as polyoxyethylene oleyl ether, the largest molecular volume oil is solubilized to a greater extent than some of the smaller molecular volume oils the most commonly used pharmaceutical oils are medium and long chain triglycerides, and esters of fatty acids such as ethyl oleate, isopropyl myristate are popular it has become common practice for researchers to screen the solubility of drug in the various components of the microemulsion, in order to predict the optimal composition of the final formulation however, extreme zantac for infants care has to be exercised when using this approach, as very often, the solubility in the final microemulsion formulation does not correlate well with that seen in the various components characterization it is noticeable that in contrast to their ease of preparation, it is very difficult to establish the microstructure of a microemulsion yet, such information is important as it may influence the drug behavior of the microemulsion in use for example, it is known that the microstructure of the microemulsion may alter the release rate of any incorporated solute currently, a range of physicochemical techniques are used to characterize microemulsions zantac for infants these techniques are often used in tandem to obtain a better picture of the system, as it is unlikely that any one technique alone will give sufficient information scattering techniques light, neutron and xray and pulsed field gradient nmr are generally used to determine the microstructure of the microemulsion one serious limitation with characterizing microemulsions is that most techniques rely on the concentration of disperse phase being low enough to avoid particleparticle interactions, as an estimated volume fraction of vol is suitable the requirement is a particular problem with microemulsions that contain cosurfactants that partition between the oil and water phases, zantac for infants because these systems frequently undergo a change upon dilution routes of administration although most of the original work exploring microemulsions as drug delivery vehicles examined their potential for oral drug delivery, microemulsions have now been explored as vehicles for most routes of administration currently, they are probably most widely studied for their potential as transdermal delivery vehicles oral microemulsions and smedds have been widely studied as oral drug delivery vehicles indeed, the first commercially available microemulsion formulation was a premicroemulsion concentrate of the lipophilic peptide, cyclosporin a this formulation, known commercially as neoral, was introduced onto the market in the late zantac for infants s and immediately attracted much attention, mainly because of the high and reproducible bioavailability it produced, but also because developments in biotechnology at that time meant that it had never been easier to produce on a large scale therapeuticallyrelevant protein and peptides unfortunately, because of their physicochemical properties, in particular their large size and poor stability, proteins and peptides are very difficult to formulate microemulsions offered an attractive solution to this problem, and consequently, most of the original exploratory studies on microemulsions as drug delivery vehicles were spent developing oral proteinpeptide microemulsion formulations proteins and peptides as the majority of therapeutic zantac for infants proteins and peptides are hydrophilic and water soluble, most studies utilizing microemulsions as vehicles for such molecules have exploited waterinoil microemulsions after cyclosporin a, which is unusually highly lipophilic, for a therapeutic peptide, the most widely studied peptide is insulin, with much of the early work in this area being performed by ritschel for example, kraeling and ritschel compared the peroral microemulsion formulation of insulin and capsule forms and determined that the microemulsion formulation increased the bioavailability of the insulin recently, more complex microemulsionbased systems have been developed in an attempt to improve the extent of insulin absorption for example, a zantac for infants recent study performed by natnasirichaiku et �� showed a significant improvement in the oral bioavailability of insulin in diabetic rats when administered in nanocapsules dispersed in a waterinoil microemulsion santiago et al have developed a new, enteric oral dosage form of insulin, in which an association of insulin and cyclodextrin contained within a microemulsion is processed into granules in the most recent study aimed at developing an oral formulation of insulin, iek et al used a conventional lecithinbased waterinoil microemulsion formulation prepared from wt water, wt labrafil m cs as oil and stabilized by wt of a weight ratio of lecithin zantac for infants phospholipon g and ethanol in addition to insulin iug water, some of the microemulsions contained the enzyme inhibitor aprotinin klug water although it is the first time that a microemulsion formulation has contained both a proteinpeptide and an enzyme inhibitor, the concept of adding an enzyme inhibitor, to a formulation containing a peptide in an attempt to reduce its degradation is not new the plasma glucose and insulin levels of the rats after intragastric administration of the formulations to both diabetic and nondiabetic rats were significantly different from those obtained after oral administration of an aqueous insulin solution although the addition zantac for infants of aprotinin to the microemulsion containing insulin increased bioavailability when compared with those not containing it, the difference was insignificant other peptides formulated as waterinoil microemulsions in an attempt to improve their oral absorption include rgb peptides, and more recently, n acetylglucosaminylnacetylmuramyl dipeptide gmdp the poor bioavailability of gmdp has been attributed to both its poor stability in the lumen of the gastrointestinal tract and its poor intestinal permeability when gmdp was administered intraduodenally in a waterinmediumchain trigylceride microemulsion, a tenfold increase in bioavailability was observed, ie a bioavailability of was achieved as opposed to , seen after administration of an zantac for infants aqueous solution of gmdp this increase in bioavailability is consistent with the work of constantinides et al,s who utilized a similar medium chain triglyceride based microemulsion to increase the oral bioavailability of the watersoluble peptide sk&f , after intraduodenal administration to rats ke et al have recently reported an attempt to develop waterinoil microemulsions suitable for the incorporation of therapeutic proteins and peptides using a medium chain triglyceride, water and tocopheryl polyethylene glycol succinate tpgs as the primary surfactant however, as tpgs could not form microemulsions when used as sole surfactant, it was mixed with a second surfactant, either tween or , zantac for infants at a weight ratio in the range of to a range of glycols and polyols were examined as cosurfactants although stable, transparent microemulsion and gel regions were identified, the extent of these regions was influenced by the precise nature and the amount of the secondary surfactant and cosurfactant for example, tween , which is an ester of the unsaturated ci fatty acid, oleic acid, was more effective in forming a microemulsion than tween , which is an ester of the saturated c fatty acid, stearic acid in this study, although the microemulsions were ultimately intended for use as delivery vehicles for protein or zantac for infants peptide drugs, they were not examined for this purpose other hydrophilic molecules other watersoluble therapeutic molecules that have been administered in microemulsions include the aminoglycoside antibiotic, gentamicin and the biologically active polysaccharide, heparin in common with all aminoglycosides, gentamicin is highly polar and is therefore considered unlikely to be absorbed from the gastrointestinal tract via simple diffusion in order to facilitate the trans mucosal delivery of the drug, hu et al, prepared a smedds formulation of gentamicin using a range of surfactants when labrasol was used as surfactant, a bioavailability of gentamicin was obtained, compared with only and when tween and zantac for infants transcutol p were respectively used labrasol was also found to inhibit intestinal secretory transport from the intestinal enterocytes, providing the formulation with the additional benefit of inhibiting the efflux of gentamicin out of the enterocytes into the gi lumen due to its low bioavailability, heparin is generally administered by injection in an attempt to formulate an orally active version of heparin, kim et al synthesized a low molecular weight heparin lmwhdeoxycholic acid doca conjugate termed lmwhdoca and formulated it in a waterinoil microemulsion using as oil, the medium chain trigylceride, tricaprylin, a mixture of tween and span surfactants, lmwhdoca and water zantac for infants volume ratios of respectively oral administration of lmwhdoca in the waterintricaprylin microemulsion to mice resulted in a bioavailability of toxicity studies suggested that the enhancement in bioavailability, observed with the docaconjugated lmwh, was administered in a microemulsion not due any local toxicity such as disruption or damaging of the intestinal membrane hydrophobic drugs a number of poorly watersoluble, low molecular weight, lipophilic drugs have also been formulated in microemulsions or smeeds for oral delivery including nitrendipine, danzol halofantrine and biphenyl dimethyl dicarboxylate these studies serve as an illustration of how important it is to understand the influence on microemulsion formation of zantac for infants the various formulation components it is worth commenting that the main use of smeeds formulations is for the oral administration of lipophilic drugs formulating nitrendipine in a smeeds formulation, composed of a ww mixture of glycerol monocaprylic ester mcg and propyleneglycol dicaprylic ester dcpg and nonionic surfactant various, was observed to significantly enhance its absorption when compared with a suspension or an oil solution and served to reduce the effect of the presence of food on its absorption however, the absorption profile of nitrendipine was seen to vary with the type of surfactant used absorption was rapid from the tween stabilized zantac for infants formulation, while the hco based formulation gave a prolonged plasma concentration profile no absorption of nitrendipine was observed from the formulation containing blex polyoxyethylene alkyl ether, ce damage to the gastrointestinal mucosa also differed with the type of surfactant employed hcoo and tween based formulations were mild to the organs, while blexbased formulation caused serious damage the study of porter et al appropriately demonstrates the effect of changing the nature of the trigylceride involved in the formulation on drug absorption these workers studied three lipidbased danazol formulations namely a longchain triglyceride solution lctsolution, a smedds based on long c chain lipids zantac for infants lcsmedds and a smeeds formulation containing medium cc chain lipids mcsmedds these formulations were administered to fasted beagle dogs and their absorption, compared with that obtained with a micronized danazol formulation administered postprandially and in the fasted state although both the lctsolution and lcsmedds formulations were found to significantly enhance the oral bioavailability of danazol, when compared with fasted administration of the micronized formulation, the mcsmedds produced little improvement in danazol bioavailability this result was partly attributed to the fact that upon digestion of the mediumchain formulation, significant drug precipitation was observed khoo et al also considered the effect of formulating zantac for infants halofantrine as a premicroemulsion concentrate in a formulation based on either a medium or long chain triglyceride both formulations, which were administered as softgelatin capsules, contained the same amount of medium or long chain trigylceride and were stabilized by the same surfactantcosurfactant mixture, consisting of cremophor el and ethanol although the plasma levels of the drug were not significantly different between the two formulations, the amount of drug absorbed lymphati cally varied in that of the dose administered in the longchain trigylceride formulation was transported lymphatically, as opposed to only of the dose administered in the mediumchain formulation kim et al zantac for infants attempted to improve the solubility and bioavailability of biphenyl dimethyl dicarboxylate, a drug used in treating liver diseases, by formulating it as a premicroemulsion concentrate in order to optimize drug loading in the formulation, these workers screened drug solubility in a range of surfactants and oils, and on the basis of these results selected tween and neobee m however, care must be taken when using this approach to optimize the formulation with respect to drug loading, as it has shown that solubility of drug in the bulk components is not a reliable indicator of solubility, in the final microemulsion formulation, the zantac for infants danger of predicting drug solubility in the final formulation, on the basis of bulk solubility, can be seen in the study of kim et al where the solubility of the drug in a formulation consisting of a weight ratio of tween to neobee m was times that of the formulation containing a tween neobee m weight ratio of , despite the solubility of the drug in neobee m being times that seen in tween the final formulation, which consisted of wt triacetin and wt tween and neobee m at a weight ratio of , greatly enhanced the oral bioavailability of bdd, possibly due zantac for infants to the increased solubility of the drug and its immediate dispersion in the gastrointestinal tract itoh et al optimized the formulation of the poorly watersoluble drug n, n[,ditertbutylhydroxyphenethyl,difluorophenyl]n [nbenzylpiperidyl] urea, by complexing it with lascorbic acid and incorporating the complex into a smeeds comprising gelucire , hco and sodium dodecyl sulfate upon dilution with water, the smeeds formulation produce a fine dispersion of nm droplets which were stable over the ph range of to the oral bioavailability of the drug was between times that which was obtained with an aqueous solution of the complex buccal to date, very little work zantac for infants has been performed on investigating the use of microemulsions as vehicles for buccal delivery in , ceschel et al, showed that the penetration of the essential oil, salvia sclarea l through porcine buccal mucosa in vitro was increased when formulated as a microemulsion, as opposed to the pure essential oil scherlund et als investigated the potential of lidocaine and prilocaine thermosetting microemulsions and mixed micellar solutions as drug delivery systems for anesthesia of the periodonlal pocket the formulations contained between wt of a eutectic mixture of lidocaine or prilocaine melting point �c, while the block copolymer surfactants, pluronic f and f, were zantac for infants present at between and wt for f, and between and wt for f f was chosen, as it is known to gel at body temperature and it is important that the formulation is easy to apply, remain at the application site, have a fast onset time, be nonirritant, and stable under normal storage conditions the ph of the formulations was varied between and most of the combinations were found to result in clear solutions, presumably oilinwater microemulsions or mixed micellar solutions, depending on the ph of the system at low ph, lidocaine and prilocaine are positively charged, and they could be zantac for infants expected to behave largely as watersoluble cationic surfactants, hence possibly forming mixed micelles on the other hand, at high ph, the drug substances are poorly soluble and could be expected to act largely as hydrophobic solutes and form the core of the microemulsion droplets parenteral in recent years, considerable emphasis has been given to the development of injectable microemulsions ow for the intravenous delivery of drug, in order to increase the solubility of the drug, to reduce drug toxicity, to reduce hypersensitivity, and to improve drug solubility and reduce pain upon injection a very recent development is the formulation of microemulsions zantac for infants as long circulating vehicles, and more recently, as drug tageting agents in addition, waterinoil microemulsions have been investigated as depot vehicles for the intramuscular delivery of drugs the first published study which established the potential of microemulsions for use in intravenous delivery was probably that of von corswant et al in ref these researchers prepared a pharmaceutically acceptable, bicontinuous microemulsion from a mediumchain triglyceride oil, polyethylene glycol and ethanol cosolvents and stabilized by soybean phosphatidylcholine and polyethylene glycolhydroxystearate prior to administration, the microemulsion required dilution with a suitable aqueous phase upon dilution, the microemulsion formed an oilinwater microemulsion with droplets of zantac for infants size between and nm, smaller than the size of the droplets in a commercial intravenous emulsion, namely intralipid from their animal studies, the authors concluded that the microemulsion they developed was suitable for administion by intravenous infusion to conscious rats unfortunately, although the researchers did determine drug solubility in the bicontinuous microemulsions, they did not report this park and kim also investigated the formulation of poorly watersoluble flurbiprofen at times its aqueous solubility into an oilinwater microemulsion suitable for intravenous administration the microemulsions were prepared using varying weight ratios of oil ethyl oleate to surfactant tween , and contained a range of zantac for infants isotonic solutions as the polar aqueous phase unfortunately, insufficient information was supplied regarding the precise compositions of the microemulsions, in particular, how much oil and surfactant were present, so as to draw conclusions about the formulation perhaps surprisingly the ratio of oil to surfactant used did not seem to have any effect on the amount of drug solubilized and that the presence of too much drug had a destabilizing effect on the microemulsion disappointingly, the pharmacokinetic parameters of flurbiprofen, after intravenous administration of flurbiprofenloaded microemulsion to rats, were also not significantly different from those of flurbiprofen in phosphate buffered saline solution zantac for infants in a later publication, park et al overcame the problem of stability seen in their earlier study by replacing the surfactant tween with lecithin and distearoylphosphatidyl ethanolaminenpolyethyleneglycol dspepeg and using ethanol as a cosolvent due to the presence of the long chain polyoxyethylene groups on the exterior surface of the microemulsion droplets, it was perhaps unsurprising that the biodistribution of flurbiprofen administered in this microemulsion was quite different in particular, reticuloendothelial uptake of flurbiprofen decreased, suggesting that it may ultimately be possible to target drugs incorporated in this microemulsion to different sites of the body as part of a series of zantac for infants papers, brime et al, and moreno et al prepared a novel amphotericin � lecithinbased oilinwater microemulsion, in an attempt to produce a formulation with less toxic effects than the currently available commercial formulation, fungizone the microemulsion which contained as oil isopropyl mystriate and a mixture of either tween or brij with lecithin as surfactant in some instances, formulation was lyophilized in an attempt to increase its stability the overall results of the toxicity studies were encouraging as the amphotericin bcontaining microemulsions exhibited a low toxicity, suggesting a potential therapeutic application zhang et alm prepared a lecithinbased smedds formulation of the drug zantac for infants norcantharidin upon dilution, the release rate of norcantharidin contained in the smeeds formulation was found to be dependent on the size of the disperse phase and the type of lecithin used interestingly, although norcantharidin was poorly soluble in the ethyl oleate and only slightly soluble in water, microemulsions containing ethyl oleate oil exhibited a significant increase in solubilization over the corresponding aqueous solution clonixic acid is currently marketed in salt form because of its poor water solubility however, the commercial dosage form causes severe pain after intramuscular or intravenous injection to improve the apparent aqueous solubility of clonixic acid and to zantac for infants reduce the pain it causes on injection, lee et al incorporated mgml clonixic acid into oilinwater microemulsions size nm prepared from premicroemulsion concentrate of castor oil, and a mixture of tween and tween surfactants present in a weight ratio of although the microemulsion formulation significantly reduced the number of rats licking their paws as well as the total licking time, suggesting less pain induction by the microemulsion formulation the pharmacokinetic parameters of clonixic acid after intravenous administration were not significantly different from those of the commercial formulation, lysine clonixinate the results of the study suggested that a microemulsion formulation is an zantac for infants alternative vehicle for clonixic acid paclilaxel taxol injection is known to cause hypersensitivity reactions consequently, he et al explored whether it was possible to prepare a nonsensitizing paclitaxel microemulsion using egg phosphatidylcholine, piyronic f ancl cremophor el as surfactants, and ethanol as cosurfactant note that there was no mention of the presence of a specific oil the study showed that for an equivalent dose, the paclitaxel microemulsion did not cause any hypersensitivity reaction, whereas taxol did in addition, the bioavailability of the paclitaxel in the new microemulsion was significantly higher and the elimination rate slower than that achieved with taxol the zantac for infants authors suggested that the drug molecules, trapped in the oil droplets, diffused into the systemic circulation slowly furthermore, the small particle size of the droplets nm meant that the microemulsion droplets could escape from uptake and phagocytosis of res infact it was previously suggested that it should be possible to modify the surface of the microemulsion droplets, with polyoxyethylene chains, to significantly improve circulation time kanga et als have recently explored the possibility of optimizing the release of paclitaxel from a seeds formulation using the polymer, plga the seeds formulation, which was a mixture of drug, tetraglycol, cremophor elp, and labrafil zantac for infants also contained plga of varying molecular weight the droplet size of the microemulsions was in the range of nm, with the systems without plga exhibiting the smaller size the release rate of paclitaxel decreased in the order of plga, plga k, plga k, and plga kgmol, suggesting that the molecular weight of plga in microemulsion could control the release rate of paclitaxel from microemulsion hong circulating microemulsions long circulating microemulsions have been suggested as an alternative formulation to long circulating vesicles on the basis of their small size, thus avoiding uptake by the res, their stability and their ability to solubilize zantac for infants lipophilic compounds more effectively than vesicles, and their ease of preparation wang et al, and junping et al,m have determined the potential of intravenous delivery systems of emulsionmicroemulsion systems based on vitamin e, cholesterol and pegooolipid in their first study, wang et �,� prepared emulsions containing part drug, parts vitamin e, parts cholesterol and parts pegdspe with the final formulation containing mg of drug in ml of saline solution although the emulsion was reported to form spontaneously on the addition of the required amount of saline, the formulation was homogenized to produce a more uniform particle size distribution of zantac for infants � nm no information was given as to the size of the droplets prior to homogenization the zeta potential and drug loading efficiency of the submicron emulsion were mv and although the size and loading efficiency of the formulation remained uncharged when stored at to �c for a year, � decomposition of the drug was observed the plasma area under the curve auc of the drug in the submicron emulsion was significantly greater than that of free drug overall, the drug in the emulsion had a lower acute toxicity and greater potential antitumor effects than the free drug, suggesting that the zantac for infants formulation is a useful tumortargeting submicron emulsion drug delivery system in a followup study, junping et al prepared microemulsions of vincristine suitable for injection using vitamin e, pegdspe and cholesterol, adding oleic acid to it the weight ratio of components used was i part drug, parts oleic acid, parts vitamin e, parts cholesterol and parts pegdspe no homogenization was used in the preparation of the microemulsion which yielded microemulsion droplets of � nm, when prepared using saline at ph note that ml of microemulsion solution contained mg of drug the adjustment the ph of the aqueous phase ph and the presence zantac for infants of oleic acid was essential for a high drug loading � , while the vitamin e was required for longterm storage of the formulation at to �c the formulation was stable, with respect to particle size, when stored at �c in the dark for year, while the loading efficiency of drug decreased by approximately , and decomposition of the drug was observed the plasma auc of the vincristine in the microemulsion was significantly greater than that of free drug as with the previous formulation, the drug in the microemulsion exhibited a low acute toxicity and a high potential antitumor effect targeted delivery shiokawa zantac for infants et al, recently reported the development of a novel, tumor targeted microemulsion formulation suitable for delivery of the lipophilic antitumor antibiotic, aclacinomycin a tumor targeting was achieved via folate linked to the exterior surface of long circulating pegylated microemulsions folate was selected because the folate receptor is abundantly expressed in a large percentage of human tumors, but it is only minimally distributed in normal tissues the basic composition of the microemulsion was pegoootspecholesterolvitarnin edrug present at a weight ratio or , molar ratio in one microemulsion, mol of folate linked pegdspe was present, another contained mol of folate linked pegdspe in a zantac for infants third, the folate was linked directly to the dspc and in the final one, no folate was present the association of the folate pegsooolmked microemulsion and folatepegaooolinked microemulsion with the target cells was and fold higher, whereas their cytotoxicity was and fold higher than those of nonfolate microemulsion respectively the folatepegsooo linked microemulsions showed fold higher accumulation in solid tumors hrs after iv injection and greater tumor growth inhibition than free drug these findings suggest that a folatelinked microemulsion is a feasible means for tumor targeted delivery of lipophilic drug this study shows that folate modification with a sufficiently long peg zantac for infants chain on the exterior of a microemulsions is an effective way of targeting the carrier to tumor cells topical delivery dermal and transdermal delivery the dermal and transdermal routes of administration offer several advantages compared with other routes of administration however, the poor permeability of the stratum corneum often limits the possibilities for choosing the topical administration route therefore, novel innovative formulations such as microemulsions that have the potential to facilitate skin permeation are of great interest the investigation of microemulsions as vehicles for cutaneous drug delivery is increasingly common as their potential is realized indeed, the cutaneous route is currently zantac for infants the most popular route of adminstration for a microemulsion microemulsions offer significant potentials as transdermal delivery vehicles, since they are robust, frequently stable to the addition of significant amounts of soluble enhancers, excipients and depending on their molecular architecture kreilgaard has reviewed the use of microemulsions as cutaneous drug delivery vehicles in in the present review, work prior to will not be dealt with in any detail in addition, due to the large amount of research in the area, the review is not exhaustive proteins and peptides recently, the transdermal route has received attention as a promising means to enhance the zantac for using dexamethasone acetate infants delivery of drug molecules, particularly peptides, across the skin, using harsh physical enhancement techniques such as iontophoresis and sonophoresis very little research has been performed, investigating microemulsions as vehicles for peptide delivery getie et al examined the skin penetration profiles of wt desmopressin acetate released from a waterinoil microemulsion comprising wt water, wt tagot span and wt isopropyl myristate however, the profile was comparable to that obtained using a standard amphiphilic cream although the amount of drug that penetrated the upper layers of the skin was significantly higher from the cream than from the microemulsion at all time intervals, within hrs zantac for infants of the applied dose reached the acceptor compartment from the microemulsion instead of from the cream within min, suggesting that the waterinoil microemulsion has potential for the systemic administration of the drug hydrophilic drugs waterinoil microemulsions have been used to enhance the penetration of water soluble drugs for example, alvarezfigueroa and blancomendez reported the in vitro delivery of watersoluble methotrexate from hydrogels using iontophoresis, and passively from oilinwater and waterinoil microemulsions prepared using either a vv labrasol plurol isostearique mixture or a vvv tween span l,octanediol mixture as surfactantcosurfactant, and either ethyl oleate or isopropyl myristate as oil all microemulsion zantac for infants formulations studied were more effective than passive delivery from aqueous solution of the hydrophilic drug, although for the microemulsions, delivery was greater from the oilinwater systems however, delivery from the microemulsions was less than that using iontophoresis, probably because of the lower solubility of drug in microemulsions than in simple aqueous solution escribano et al attempted to improve the transdermal permeation of sodium diclofenac four formulations were studied one was an oilinwater microemulsion based on transcutol wt, plurol oleique wt, water wt, isostearyl isostearate wt and labrasol wt the other three formulations were cosolvent systems prepared from various of the ingredients zantac for infants used for the microemulsion formulation in this study, the microemulsion performed less well than the various cosolvent formulations and in a similar manner to an aqueous solution of the drug this observation is perhaps not surprising as various enhancers were involved in the microemulsion droplets and were not available to improve drug penetration also, as it is likely that the drug was predominately in the continuous phase of the microemulsion, it is not surprising that the formulation behaved in a similar manner to an aqueous solution the in vitro transdermal permeation of the antineoplastic, fluorouracil, incorporated at imgml in waterinoil microemulsions zantac for infants prepared using aotwaterisopropylmyristate has been studied by gupta et al these researchers found that as the water content increased from and ww, microemulsions prepared with a surfactant to oil ratio of showed and fold increases respectively in the skin flux of fluorouracil, compared with an aqueous solution of drug increasing the surfactant oil weight ratio from through to , at fixed watersurfactant content of , gave , and fold enhancements of drug flux in their study used attenuated total reflectancefourier transform infrared spectroscopy to determine that the microemulsions exerted their enhancement by interacting and perturbing the architecture of the statun corneum the extent of zantac for infants this perturbation was dependent upon the concentrations of water and aot in the microemulsion preliminary toxicity studies suggested that the microemulsions were a suitable vehicle for transdermal delivery amphiphilic drugs jurkovic et al have investigated the formulation of the amphiphilic antioxidant ascorbyl palmitate in a microemulsion, with a view to using the formulation as a protectant against free radical formation due to uv irradiation both oilinwater and waterinoil microemulsions were prepared using a medium chain triglyceride as oil, and peg capryliccapric glycerides labrasol and polyglyceryldioleate, plurol oleique as surfactant and cosurfactant the ascorbyl palmitate was incorporated into the microemulsions at various zantac for infants concentrations between wt the microemulsions were gelled using either xanthan gum waterinoil or aerosil waterinoil the effectiveness of the ascorbyl palmitate in the microemulsions depended on both the concentration and type of microemulsion regardless of the type of microemulsion, efficacy was significantly higher at the higher ascorbyl palmitate concentrations overall, the oilinwater microemulsions were more effective at protecting against uv irradiation, although they delivered ascorbyl palmitate to the skin at a slower rate than the waterinoil microemulsions the effect of formulation composition on the in vitro release rate of the amphiphilic drug, diclofenac diethylamine, from a range of microemulsion vehicles containing zantac for infants peg capryliccapric glycerides surfactant, polyglyceryl dioleate cosurfactant, isopropyl myristate and water was determined by djordjevic the phase behavior of the microemulsions was determined in the absence of drug in the microemulsions selected for further study, the level of water present ranged from to wt while the amount of oil varied from to wt the physicochemical characterization studies indicated the microstructure to be either bicontinuous or nonspherical, and despite its amphiphilic nature, the drug was partitioned mainly in the water phase the nonlinearity of the drug release profile from the bicontinuous microemulsions was thought to be due to a complex distribution of zantac for infants drug within the microemulsion the flux of the drug increased by times, from a water inoil to an oilinwater microemulsion, the release of drug from the bicontinuous microemulsion, suggesting that the microstructure hampers the release of the drug hydrophobic drugs dalmora and oliveria and dalmora et al, investigated the release of piroxicam encapsulated in jcd in cationic oilinwater microemulsions, in an attempt to optimize the drugs delivery the results demonstrated the potential of the reservoir in vivo system following the use of a microemulsion the high degree of retention of the active substance can provide a means for modulating the antiinflammatory zantac for infants effect, by greatly extending the release period relative to those formulations where the piroxicam is only dissolved or dispersed in a homogeneous aqueous medium in conclusion, both microemulsions and cdcontaining microemulsions can offer many promising features for their use as topical vehicles for piroxicam delivery some of the microemulsions gelled using carbopol paolino et al examined the potential of oilinwater microemulsions as topical drug vehicles for the percutaneous delivery of ketoprofen microemulsions were prepared using triglycerides as oil, and were stabilized by a mixture of lecithin and �butanol as a surfactantcosurfactant system the percutaneous enhancer, oleic acid, was added to some zantac for infants of the microemulsions physicochemical characterization of the microemulsions yielded a mean droplet size of nm and a negative zeta potential of mv in the absence of oleic acid and � mv in its presence the ketoprofenloaded microemulsions showed an enhanced permeation through excised human skin with respect to conventional formulations, although no significant percutaneous enhancer effect was observed in the presence of oleic acid microemulsions showed a good human skin tolerability on volunteers shukla et al have investigated the potential of oilinwater �w microemulsions as vehicles for the dermal delivery of a eutectic mixture of lidocaine lignocaine and prilocaine, which acted zantac for infants as the oil phase the microemulsion was stabilized by a blend of a ratio tween and poloxamer , a mixture of water and propylene glycol were used as the hydrophilic phase these microemulsions were able to solubilize up to wt of the eutectic mixture in an attempt to enhance the transdermal delivery of the poorly water soluble drug, triptolide, and to reduce the toxicity problems associated with its usage, a waterinoil microemulsion was compared with that of solid lipid nanoparticles the microemulsion which was formulated using wt isopropyl myristate, wt tweenl,propylene glycol , vv and water and contained wt of triptolide, gave zantac for infants a steadystate flux for over hours and a permeability coefficient of triptolide of � mgcm per h and � cmh a value which was approximately double that of the solid liquid nanoparticles and times higher than that of triptolide solution of the same concentration in another study, chen etal also studied the incorporation of the drug, into a similar microemulsion using oleic acid as oil oleic acid was added because it is a known penetration enhancer, although there was no evidence of it acting as such in the present formulation the addition, however, of wt menthol to the formulation slightly increased zantac for infants penetration from � to � igcm per h p encouragingly, no obvious skin irritation was observed for the formulation studied, suggesting that microemulsions are promising vehicles for the transdermal delivery of triptolide ross et al examined the transdermal penetration, across full thickness hairless mouse skin, of the insect repellant, n,ndiethylmtoluamide deet, contained in either a vv ethanolwater solution containing wt deet or one of two commercially available microemulsion formulations m ultrathon insect repellant containing wt deet m, st paul, mn, and sawyer controlled release deet formula sawyer products, safety harbor, fl both formulations were of interest because they were marketed zantac for infants as retarding the absorption of deet due to being microemulsions all of the deet preparations exhibited considerable penetration, eg, the ethanolic deet formulation had a time to detection of approximately min with steady stale at min the penetration obtained with the sawyer was no different from that obtained from the ethanolic solution the other microemulsion formulation m demonstrated a different profile despite being a higher concentration of deet wt versus wt and a comparable time to detection min, the time to reach steady state was delayed, although there was still substantial absorption at steady state sintov and shapiro prepared a high surfactant lidocaine microemulsion, containing as surfactant a mixture of glyceryl oleate and either peg stearate or peg hydrogenated castor oil, isopropyl myristate as oil, tetraglycol as cosurfactant, water, and up to wt of drug, although wt was generally used the microstructure of the microemulsion went from oilinwater, through bicontinuous to waterinoil the penetration of the drug from the various formulations showed that the surfactant mixture containing peg stearate was best, while the water and surfactantcosurfactant concentration was also important significantly, the lag time for penetration was reduced, suggesting that these microemulsions loaded with drug would provide rapid local analgesia priano et alu?