Growing interest in microemulsions


Recently there is a turning involvement in microemulsions due to their drug transporting ability. Microemulsions are known to increase the efficaciousness of drugs by bettering their sustainability and controllability of action hence doing them more mark oriented without modifying the construction of medicative compound. Piroxicam is utile in the intervention of rheumatoid arthritis, degenerative arthritis and traumatic bruises with GI side effects. It is possible to work out these jobs by presenting drug bearers which may better the disposal of drug with minimisation of side effects due to command of drug release mechanism.

Microemulsions have good known belongingss and are extensively reported in literature e.g.optically isotropous, crystalline and thermodynamically stable homogenous solutions of oil and H2O, stabilized by add-on of a a cosurfactant. Oil in H2O microemulsions can be used for the topical application of drugs due to ( a ) their high solubilization capacity every bit good as their favorable thermodynamic interaction with tegument which make them more active towards tegument ( B ) favorable partitioning locally ( degree Celsius ) decrease of diffusional barrier by o/w microemulsion.

Extensive physicochemical word picture of an emulsion is indispensable before it can be made ready to be used for application in pharmaceutical industry. Pharmaceutical application require usage of biocompatible ingredients which may non do any type of toxic consequence while interaction with a human organic structure. The microemulsion must be stable while applied in the physiochemical conditions. The microemulsion while loaded must be stable and this can be confirmed by suited word picture of ME ; with and without the burden of medicative compound. The microstructural alterations are of great importance in this respect and physicochemical conditions must be satisfied for successful use of ME Different techniques such as conduction, viscousness, denseness, surface tenseness and the fluorescence investigation surveies are utile for supervising these alterations. The release of drug depends on the type of ME and the mechanism of release followed which depends on the type of ME and drug e.g release will be faster for a hydrophilic drug in instance of o/w microemulsion.

In this work, a microemulsion system is constructed for ailing H2O soluble non-steroidal anti-inflammatory drug Feldene, comprising of Castor oil, a non-ionic wetting agent Tween 80, a cosurfactant ( ethyl alcohol ) and phosphate buffer ( PB ) of pH 7.4. The pseudo-ternary stage diagram has been constructed for this peculiar system at a changeless wetting agent to cosurfactant ratio ( 1:2 ) . Castor oil has a hydroxyl group in add-on to unsaturation, doing it more polar and its ethoxylates are normally used as emulsifiers in many applications. Polyoxyethylene fatty acid, stearic acid, oleic acid are used in emulsifiers in oil/water type pick and lotions. Castor oil shows anti-inflammatory effects due one of its major constituent called ricinoleic acid. Conductivity, viscousness and surface tenseness are employed to look into the gradual alterations happening in the microstructure of microemulsion. It is expected that the usage of microemulsion preparation may better the solubility of Feldene and avoid its debasement.

Materials and Methods


Tween 80 ( polyoxyethylene sorbitan monooleate ) , absolute ethyl alcohol ( 99.8 ? % ) and castor oil were purchased from Fluka. Pyrene ( 98 % ) was purchased from Sigma-Aldrich. Piroxicam was liberally provided by “Amson Vaccines & A ; Pharma ( PVT ) Ltd” and used without farther purification. Phosphate buffer ( 0.01 M, pH 7.4 ) was used as the aqueous stage. Buffers were prepared utilizing NaH2PO4/Na2HPO4. 0.1M NaOH and HCl were used to keep the pH of the solution.


Microemulsion Preparation

The pseudo-ternary stage diagram was delineated ( as shown in Fig. 1 ) utilizing oicastor oil, wetting agent ( Tween 80 ; HLB = 15 ) , cosurfactant ( ethyl alcohol ) and aqueous stage PB ( pH 7.4 ) at 25±0.01 ?C with changeless wetting agent to cosurfactant ratio ( 1:2 by mass ) . The temperature was maintained at 25±0.01 ?C utilizing a Lauda M-20 thermoregulator. Initially castor oil was added to Tween 80/ethanol mixture and the PB was added dropwise to obtain the coveted microemulsion composings. Transparent, single-phase mixtures were designated as microemulsions. All the samples were stable for over 10 months, staying clear and transparent.

Table 1: Selected microemulsion preparations ( % , w/w )









* ME

Castor Oil




















Tween 80










Ethyl alcohol










*Selected Microemulsion ( ME ) for farther analysis

Drug incorporation in Microemulsion

A set of microemulsions, as given in the table1, differing from each other in weight fractions ( Fw ) were selected from the single-phase part as given in Fig. 2 to analyze their physicochemical belongingss. All of them were stable over 10 months and did n’t shown any marks of stage seperation. A 1 % w/w composing of Piroxicam was prepared by dissolvingthe it into pre-weight oil constituent of the systemunder stirring followed by add-on of staying constituents.

Microemulsion Characterization

Optical Transparency

Polarimetry and ocular scrutiny were used to analyze the optical transparence of the pure drug loaded microemulsion. The theoretical account of the Polarmeter instrument for this intent was ATAGO, AP-100 Automatic Polarimeter. All these scrutinies were performed at the room temperature.Centrifugation

Drug Loaded and pure samples of ME were centrifuged at 5500 revolutions per minute to look into their thermodynamic stability.Each sample was centrifuged at 5500 revolutions per minute for 20 min utilizing ( Hermle Z200 ) extractor.

Surface Tension

A tortuosity balance ( White Elec. Inst. Co. Ltd. ) was used to mensurate the surface tenseness at 25 ±0.01?C under atmospheric pressureThe perimeter of the ring for the measuring was 4.0cm. An experimental mistake of ±0.05 mNm-1 was estimated.

Density and Specific Gravity

Densities and Specific Gravity of pure and drug loaded microemulsion samples were measured by utilizing an Anton Paar ( Model DMA 5000 ) denseness metre at 25 ±0.01 ?C. Caliberated denseness metre was used for executing the measurings. Density of air and pure H2O are used as criterions for caliberation.

Refractive Index

The refractile indices of the samples were by experimentation determined utilizing a refractometer ( ATAGO, RX-5000 ) by puting a bead of solution on the slide.


The pH of all the selected pure ME samples and the drug loaded ME was determined at room temperature utilizing a pH Meter ( WTW 82362 Weilheim ) fitted with a pH electrode ( WTW A061414035 ) . The temperature was kept changeless ( 25±0.01 ?C ) utilizing a Lauda M-20 thermoregulator.

Conduction Measurements

Electrical conduction is a suited tool for the measuring of the consequence of the sum of H2O stage of microemulsion. Microprocessor Conductivity Meter ( WTW 82362 Weilheim ) fitted with an electrode ( WTW 06140418 ) holding a cell invariable of 1.0 cm-1 was used for the intent of measuring of conduction ( ? ) . Conduction measurings were carried out by titration of oil and surfactant/cosurfactant mixture with buffer ( along the dilution line AB in Fig. 1 ) . The conduction of selected and drug loaded microemulsions was besides measured. The mistake bound of conductance measurings was ±0.02 ?scm-1.

Viscosity Measurements

Viscosities were measured with graduated Ubbelhode viscosimeter at 25±0.1 ?C. For each measuring, the viscosimeter was washed, rinsed and vacuum dried. To follow the syrupy behavior of the microemulsions, flow clip was measured for all the selected and drug-loaded microemulsions ( 1 wt % drug ) . The mistake bound of viscousnesss measurings was ±3 % .

Consequences and Discussion

Castor oil, a fatty acid, known for its high permeableness, was used to fix ME system [ 18-20 ] . A non-ionic wetting agent, tween-80 is used due to its abundant use in commercial preparations of pharmaceutical due to its non-toxic nature [ 21-23 ] where ethyl alcohol was used a co-surfactant so that there is no demand for any input of extra energy and do the so formed composing ready as a possible drug bearer system.. [ 24-26 ] . Before the add-on of aqueous stage, a so called oily stage consisting merely of wetting agent, oil, and ethanol exists. Ethanol affects its critical wadding parametric quantity ( CPP ) of tween 80 as cited in literature and is known to stamp down the formation of unwanted stages. When H2O is bit by bit added to the so called oily stage, it favors the organisation of the caput groups of the tween 80 into a polar nucleus while the fatty acid dress suits are oriented such that they are present in the oil uninterrupted stage.

Phase Surveies

Tween-80/ethanol/castor oil/buffer at 25 ?C.

Phase behavior probes of this system demonstrated the suited attack to finding the H2O stage, oil stage, surfactant concentration, and cosurfactant concentration with which the transparent, 1-phase low-viscous microemulsion system was formed. The stage behaviour exhibits a two-phase part, a three-phase part and a big single-phase part which bit by bit and continuously transformed from buffer rich side of binary solution ( buffer/surfactant micellar stage ) of pseudo-ternary stage diagram towards the oil rich part. This laid an accent on a uninterrupted passage from H2O rich composings to oil swollen micelles.

The stage survey revealed that the maximal proportion of oil was incorporated in microemulsion systems when the surfactant-to-cosurfactant ratio was 1:2. From a preparation point of view, the increased oil content in microemulsions may supply a greater chance for the solubilization of Feldene. Eight microemulsions ( 1-8 ) were selected from the single-phase isotropic part ( Fig. 2 ) , with composings mentioned in Table 1. Selected Microemulsion ( ME ) was farther analyzed by conduction, viscousness, denseness, surface tenseness, refractile index and pH. The values of measured parametric quantities have been presented in Table 2.

Table 2: Physical Parameters of Selected Microemulsion ( ME ) & A ; after Incorporation of Drug

Physical Property

Second: CoS = 1:2


( no drug )


( drug loaded )

Refractive Index



Conductivity ( ?s/cm )



Kinematic Viscosity ( cPLg-1 )



Density ( gL-1 )



Viscosity ( cP )



Surface Tension ( mN/m )



Specific Gravity






Conduction Measurements

Conductometry is a utile tool to measure microemulsion construction. Conductivity surveies have elucidated the being of a characteristic zone with an isotropous microemulsion sphere in a continuum. Electric conduction ( s ) was measured as a map of weight fraction of aqueous constituent Fw ( % wt ) for the oil, surfactant/cosurfactant mixture along the dilution line AB ( shown in Fig. 2 ) . The consequences of fluctuation of s V Fw ( % wt ) are shown in Fig. 3 ( a ) . The behavior exhibits profile feature of percolative conduction. The conduction is ab initio low in an oil-surfactant mixture but increases with addition in aqueous stage.

While the H2O volume fraction additions, the electrical conduction of the system somewhat increases every bit good until the critical Fw is reached when a sudden addition in conduction is observed. This phenomenon is known as infiltration, and the critical Fw at which it occurs is known as infiltration threshold Fp.

The value of conduction below Fp suggests that the contrary droplets are distinct ( organizing w/o microemulsion ) and have small interaction. Above Fp the value of s additions linearly and steeply till it touches the value of Kb. The interaction between the aqueous spheres becomes increasingly more of import and forms a web of conductive channel ( bicontinuous microemulsion ) [ 30 ] . Beyond the infiltration threshold ( Fp ? 6 % ) conduction increases linearly and aggressively up to ( Fw ? 20 % ) . It can be concluded that beyond Fp a web of conductive channels exists, which corresponds to the formation of H2O cylinders or channels in an oil stage due to the attractive interactions between the spherical micro-droplets of H2O stage in the w/o microemulsion. With farther addition in H2O content, above Fb ( Fw & gt ; 20 % ) , the s shows a crisp lessening, which may be due to strong attractive forces as system becomes more syrupy [ 15, 30 ] . Fig. 3 ( B ) depicts the fluctuation of log s V weight fraction of H2O ( Fw ) . The alteration in the incline of log s can be interpreted, as a structural passage to bicontinuous from w/o, about at Fw = 6 % . The passage takes topographic point one time the aqueous stage becomes uninterrupted stage i.e. at Fb. This is in line with the observation made in stage survey. Therefore, the s V Fw secret plan illustrates happening of three different constructions ( viz. w/o, bicontinuous, o/w ) . The conduction of the microemulsions incorporating more than 20 wt % H2O decreased significantly, likely due to the higher viscousness.

The infiltration threshold can be determined from the secret plan ( ds/dFw ) , as a map of the H2O weight fraction, Fw ( % wt ) . A upper limit in the first derived function of conductance Fw at ~12wt % H2O is observed ( Fig. 4 ) corroborating the presence of infiltration behaviour ( bicontinuous microstructure ) in this part [ 31 ] . The electric conduction of pure selected and drug loaded microemulsion ( 1.0 % ) is given in Table 2. A comparing of two systems shows that drug incorporation does non impact the microstructure of the microemulsion.

Viscosity Measurements

To avoid the ambiguity of likely non-Newtonian flow behaviour of microemulsion the flow clip has been used as an index of viscousness. Flow clip of oil, surfactant/cosurfactant mixture along the dilution line AB ( shown in Fig. 2 ) , was measured as a map of weight fraction of H2O Fw ( wt % ) and is shown in Fig. 5. Similar tendency has been observed for the viscousness of oil, surfactant/cosurfactant mixture as a map of Fw ( Fig. 6 ) . The rapid alteration in the viscousness is likely due to the alteration in the microstructure of the microemulsion. The alteration in the internal construction could be due to either the alteration in the form of droplets or may be due to the passage from w/o to bicontinuous microemulsion. It is good known that addition of volume fraction of spread stage in microemulsion additions viscousness of the system.

For the system studied viscousness additions with addition in Fw ( wt % of aqueous stage ) . Difference in the viscousnesss is more profound for lower H2O content values in comparing to the dilute system. The microemulsion system is turning to be more syrupy with add-on of H2O and therefore may assist in the slow diffusing of drug at infinite dilution. The microemulsion system therefore, shows a structural alteration from oil uninterrupted system to H2O uninterrupted, which has higher viscousnesss than the former. The secret plans of hk ( kinematic viscousness ) , d2?/d2Fw and 1/? d?/dFw versus Fwreflect that the passage occurs at ~11 % weight fraction of aqueous stage ( Fig. 6 ) . The passage point of surface tenseness, conduction and viscousness secret plans coincides good at ~11 % weight fraction of aqueous stage and confirms the presence of percolative behaviour.

Surface Tension

The surface tenseness additions linearly over the same scope of H2O content ( Fig. 7 ) , but two interruptions ( at ~7.0 and ~20 wt % H2O ) suggest that construction alterations occur at these composings. The surface tenseness measurings showed increase, when measured as a map of weight fraction of aqueous constituent, expect for the ~12 % weight fraction where the value all of a sudden decreased and thenceforth a regular addition was observed. This low surface tenseness value showed the presence of bicontinuous microemulsion between oil and H2O rich system, which is because of presence of self-assembled organize microstructure in it [ 13, 35, ] . The consequences coincide good with the electric conduction and viscousness measurings. It can be assumed that the added intoxicant ( ethyl alcohol ) is incorporated in the interfacial construction in such a manner that more H2O is on the exterior of the “oil drops” , doing the addition in surface tenseness. Incorporation of drug showed a negligible alteration in the surface tenseness measurings, hence indicting the possibility of Feldene molecules into the palisade bed on the interior side of microemulsion.


A pseudo-ternary stage diagram was successfully constructed for the system under probe i.e. , Tween 80/ethanol/castor oil/buffer. The conduction and viscousness surveies along the dilution line ( in stage diagram ) depict the Structural passage from w/o to o/w via bicontinuous stage at ~11 % ?w ( wt % fraction of aqueous stage ) was supported by conduction and viscousness informations. Among the selected microemulsions ( I-VIII ) , MEX was found to be best possible, stable and optically clear, composing for the incorporation of Feldene The surface tenseness and fluorescence surveies indicated that the drug may shack at the interface of oil and aqueous stage. The ME system was successfully applied to increase the solubilization of drug.


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