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    by: jaya

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    1 : MICRO EMULSIONS PRESENTED BY Y.JAIRAM KUMAR M. Pharmacy
    2 : CONTENTS ?INTRODUCTION ?ADVANTAGES OF MICRO EMULSIONS ?DIFFERENCES BETWEEN EMULSION&MICROEMULSION ?TYPES OF MICRO EMULSIONS ?FORMULATION AND PHASE BEHAVIOUR ?TECHNIQUES ?APPLICATIONS ?CONCLUSION ?REFERENCES
    3 : Microemulsions ?Microemulsions are thermodynamically stable, optically transparent, isotropic dispersions of aqueous and hydrocarbon liquids stabilized by an interfacial film of surfactant molecules ?Microemulsions show diverse structural organizations due to wide range of surfactant concentrations, water-oil ratios, temperature etc...
    4 : ?The surfactant used in these formulations are known to improve the bioavailability by various mechanisms including A) Improved drug dissolution B) Increased intestinal epithelial permeability C) Increased tight junction permeability D) Decreased/inhibition of p-glycoprotein efflux
    5 : Advantages of Microemulsions: ?Microemulsions act as supersolvents of drug. They can soluble hydrophilic and lipophilic drugs including drugs that relatively insoluble in both aqueous and hydrophilic solvents. ?Improvement of bioavailability of antifungal and anti-inflammatory drug by topical micro emulsion. ?The mean diameter of droplets in micro emulsions is below 0.22µm; they can be sterilized by filtration.
    6 : ?Some microemulsions can carry both hydrophilic and lipophilic drugs ?Microemulsions have low viscosity compared to other emulsions. ?The formation of microemulsions is reversible. They may become unstable at low or high temperature, but when the temperature returns to the stability range, the micro emulsions reformed.
    7 :
    8 : Types of Microemulsions: ?O/w Microemulsion ?Bi continuous Microemulsion ?W/o Microemulsion
    9 : Structure of Microemulsion: ? Microemulsions are the spherical or cylindrical structures formed by the aggregates of micelles that are formed by surfactants at the oil/water interface. ? Micelles are drops of oil in water interface and reverse micelles are like drops of water in oil
    10 : ?Another microemulsion structure is the lamaelle, where water and oil consective layers are separated by surfactant. ?The lamaelle is similar to the smectic thermotrophic phase. It maintain the order even at dilution concentrations. ? This structure is related to the spherulute structure [onion structure]
    11 : ?The bicontinuous structure or sponge phase. In this both oil &water are continuous phase. ?The pipeline forms an oil continuous phase and the exterior forms a water continuous phase
    12 : ? Other microemulsions structure are possibly interconnected rod-like micelles with an inner different structure, vesicles, etc…
    13 : SOLUBILITY STUDIES: ?The microemulsion formulations consist of 1 or 2 more surfactants in combination with co-surfactant and drug dissolved in oil. ?The mixture is a clear, monophasic liquid at temperature and passes good solvent properties to allow presentation of the drug in solution. ?Oils form distinct core in the interior of the surfactant aggregate, results in enhanced solubilising capacity of the oils with improved drug loading capacities of the microemulsion.
    14 : FORMULATION: ?Microemulsion formulation involves a combination of three or five components. a) An oily phase b) An aqueous phase c) Primary surfactant d) Secondary surfactant e) Electrolyte
    15 : SURFACTANT ?Surfactant must able to low interfacial tension to a very small volume to aid dispersion process during the preparation micro emulsion. To provide a flexible film that can readily deform round droplets The appropriate lipophilic character to provide a correct curvature at the interfacial region for the desired micro emulsion.
    16 : combination of anionic or cationic surfactants of high HLB with a co- surfactant of low HLB, a single chain non- ionic surfactant of the poly ethylene glycol alkyl ether at appropriate temp. are generally used for the formulation of micro emulsion. examples: span 8O, tween 6O, polyoxy ethylene lauryl ether sodium dodecyl sulphate
    17 : CO-SURFACTANT ? It is generally not possible to achieve a required interfacial area with the use of single surfactants, if however co- surfactant is added to the system. ?An essential requirement for the formation and the stability of micro emulsion is attained at very low interfacial tension. Since micro emulsion have very large interphase between oil and water because of small droplet size, they can only be thermo dynamically stable.
    18 : OILS ?The oil component influence curvature by its ability to penetrate and hence swell the tail group region of the surfactant mono layer. ?Short chain oils penetrate the tail group region to grater extent than long chain alkanes, and hence swell this region to a grater extent, resulting in an increasing negative curvature Example: Triglycerides like labrafac, lauroglycol, and olive oil.
    19 : TEMPERATURE: ?It plays an important role in the formulation of microemulsion when an non-ionic surfactant is used. ?At low temperature, non-ionic surfactant are hydrophilic and form o/w microemulsion, at high temperature, they are lipophlic and form w/o microemulsion. ?At an intermediate temperature, hydrophilic-lipophilic interactions just balance and form bicontinuous microemulsion
    20 : SURFACTANT- CO-SURFACTANT RATIO The surfactant & co-surfactant ratio is a key factor in influencing the phase properties. Attwood et al … showed how size and location of micro emulsion is changing on changing in amass ratio of polysorbate 40 / sorbitol from 1:1 to 1: 3.5 ratio. Such effects are attributed to difference in the packing of surfactant and co surfactant at the oil / water interphase.
    21 : Diagram representation of micro emulsion preparation
    22 : PHASE BEHAVIOUR: ?Oil, water and surfactants are mixed, microemulsions are the one of the number of association structures { including emulsion, lamellar, micelles, cubic and hexagonal} that can form depending up on the composition. ?A quaternary phase diagram is time consuming is difficult to interpret, pseudo ternary phase diagram is constructed to find out the different zones of micro emulsions.
    23 : Ternary phase diagram of oil, water and surfactant of microemulsion formation zone
    24 : ?In each corner of diagram represents 100% of the particular component. ?Micro emulsion can also exists in equilibrium with excess water, excess oil or both, which are known as winsor Type 1,2,&3 systems. ?The winsor type 1 system consists of a lower phase o/w micro emulsion with excess of oil.
    25 : ?Type 2 consists of upper phase of w/o micro emulsion with excess of water. ?Type 3 system form when the surfactant are concentrated in surfactant rich bicontinuous middle phase which co exists with both water and oil.
    26 : Winsor Type I,II,&III Microemulsion:
    27 : Techniques for characterization of Microemulsions: 1) Scattering techniques 2) Nuclear magnetic resonance studies 3) Electron microscopic 4) Interfacial tension and viscosity measurements
    28 : Scattering techniques: ?Small-angle x-ray scattering (SAXS), small-angle neutron scattering (SANS), and static as well as dynamic light scattering are widely applied techniques in the study of microemulsions. ? Static scattering techniques, the intensity of scattering light are measured at various angles and for different concentration of microemulsion droplets. The intensity of scattering radiation is measured as a function of the scattering vector q, Q= (4?/?) sinO/2 Where O is the scattering angle ? is the wave length of the radiation ? These methods are use to obtain quantitative informations on the size, shape and dynamics of the components.
    29 : Nuclear Magnetic Resonance Studies: Structure and dynamics of microemulsion. ? Self-diffusion measurements using different tracer techniques, generally radio labelling. ?The Fourier transform pulsed-gradient spin-echo (FT-PGSE) technique uses the magnetic gradient of the samples.
    30 : Electron Microscopic Studies: The images showing clear evidence of the micro structure has been obtained. ? Freez-fracture electron microscopy has also been used to study microemulsion structure.
    31 : Interfacial tension: ?The formation and the properties of microemulsion can be studied by measuring the interfacial tension. ? Spinning-drop apparatus can be used to measure the ultra low interfacial tension.
    32 : Viscosity Measurements: ?Viscosity measurements can indicate the presence of rod like or worm-like reverse micelle. ?Viscosity measurements as a function of volume fraction have been used to determine the hydro dynamic radius of droplets .
    33 : Applications of Microemulsions: ? oral drug delivery ? Topical drug delivery ? ocular and pulmonary delivery ? parenteral administration ? preflouro microemulsions ? microemulsions in biotechnology. ? Solubilization of drugs in microemulsions ?influence on drug release characteristics
    34 : Oral Drug Delivery: ? The recent advances in pharmaceutical and biotechnology permits rather high amounts of peptides and proteins to be produced. ? Short half-life, stability, biodegradability of these molecules cause considerable design difficulties in their formulation for oral administration. ?Micro emulsions extensively studied for protection of biodegradable drugs.
    35 : Example: ?Cyclosporine is an immunopotent drug widely used in transplants. It has very poor bioavailability after oral administration. ?w/o microemulsion were administrated to rat per orally and it was found that for one of them, the absolute and relative bioavailability were better than that of commercially available solutions. ?A cyclosporine preparation using w/o microemulsion containing a sorbiton ester-polyoxyethylene glycol mono ether mixture of surfactant, a low molecular weight alcohol fatty ester and water as the vehicle for the drug was administered.
    36 : Topical drug delivery: ? Transdermal drug delivery system exhibits several advantages than oral route, by avoiding systemic side effects. ? But the main limiting factor for this delivery system is penetration of drug through stratum corneum, which comprises keratin rich dead cells embedded in a lipid matrix. ?Considering the solubilising capacity of microemulsion, these are expected to significantly affect the structure of the stratum corneum lipid self-assembles, with obvious consequences for drug penetration.
    37 : Example: ? Lecithin containing w/o microemulsion of scopolamine and broxaterol was used for the transdermal administration and found that the transport rate obtained with the lecithin microemulsion gel was much higher than that obtained with an aqueous solution at the same concentration.
    38 : Parenteral Administration: ? In order to attain prolonged release and to administer parenterally lipophilic substances that are not soluble in water, o/w microemulsion may be used as carriers. ?They can be administrated by intravenous, intramuscular, subcutaneous route. The potential of o/w microemulsions as a vector for fluorocarbon, calcium antagonist, steroids and other lipophilic drugs. ?o/w microemulsion containing very lipophilic drugs to reticuloendothelial system i.e.. liver and spleen. The results indicted that higher the partition coefficient of the drug
    39 : Micro emulsion in Biotechnology: ?Many enzymatic and biocatalytic reactions are conducted in pure organic or aqua- organic media. ?Biphasic media also used for these type of reactions. ?The use of pure polar media also causes the denaturation of biocatalysts. The use of water-poor media is relatively advantageous. ?Enzymes in low water content display and have a) Increased solubility in nonpolar reactants b) Improvement of thermal stability of the enzymes
    40 : Conclusion ? Microemulsion properties are extremely varied. The extreme diversity of their practical applications is one consequence. ?One of their disadvantages is the large amount of surfactant required to stabilize them because of the small dispersion size. ? Although microemulsion properties are beginning to be satisfactorily understood, especially the droplet structure, large research domains remain to be clarified.
    41 : REFERENCES Schulman, JH Stoechenius, W., Prince. L.M.J.Phys. Chem, 1959,63,1677-80 Shinoda, K.Lindmann, B.Langmuir, 1987,3,135-49 Danielson, I., Lindmann, B.Colloids and surfaces.1992,3,391-2 Lawrence M.J.Rees G.D.Adv Drug DEL.Rev,2000,45,89-121 Bagwe, R.P., Kanicky, J.R., Palla, B.J.Patanjali, P.K., Shah, D.O.Crit Rev, Ther. Drug Carrier Syst., 2001. 18, 77-140
    42 : THANK U

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