Micro emulsions and multiple emulsions

1. MICRO-EMULSIONS& MULTIPLE EMULSIONS PRESENTED BY CH.Leena madhuri 256212886009 M.PHARMACY (SEMESTER-II) DEPARTMENT OF PHARMACEUTICS

2. CONTENTS  INTRODUCTION  ADVANTAGES OF MICRO EMULSIONS AND MULTIPLE EMULSION  DIFFERENCES BETWEEN EMULSION&MICROEMULSION  TYPES OF MICRO EMULSIONS AND MULTIPLE EMULSIONS  FORMULATION AND PHASE BEHAVIOUR  TECHNIQUES  APPLICATIONS  CONCLUSION  REFERENCES

3. DEFINITON:- Emulsions are defined as thermodynamically unstable heterogenous systems, in which one immiscible liquid is dispers in another phase in the form of droplets & stabilised by third component called emulsifying agent. Simple emulsions are 2 types: W/O system O/W system

4. 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...

5. ►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

6. Advantages of Microemulsions: ►Micro emulsions are simple and economic. ►They have long term stability and enhanced bioavailability. ►High solubilization capacity for hydrophilic and lipophilic drugs. ► Various routes like topical, oral and intravenous can be used to deliver the product ►Micro emulsions have low viscosity compared to other emulsions.

7.  DIFFERENCES

8. 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

9. 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 SURFACTANT

10. 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.

11. 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 , lauroglycol, and olive oil.

12. 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

13. The drug is be dissolved in the lipophilic part of the micro emulsion i.e. Oil and the water phases can be combined with surfactant and a co surfactant is then added at slow rate with gradual stirring until the system is transparent . Gel may be prepared by adding a gelling agent to the above micro emulsion. Carbomers (crosslinked polyacrylic acid polymers) are the most widely used gelling agent. PREPARATION OF MICRO EMULSION

14. PHASE BEHAVIOUR:  Oil, water and surfactants are mixed, micro emulsions 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 . pseudo ternary phase diagram is constructed to find out the different zones of micro emulsions.

15.  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.

16.  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.

17. Techniques for characterization of Microemulsions: Micro emulsions have been evaluated using a wide range of different techniques: At the microscopic level,viscosity,conductivity and dielectric methods provide useful information. Conductivity measurements provide a means of determining whether a microemulsion is oil- continous or water- continous and provide a means of monitoring percolation and phase inversion phenomena. Dielectric measurements are a powerful means of probing both the structural and dynamic features of microemulsion system.

18. 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 micro emulsions.  Static scattering techniques, the intensity of scattering light are measured at various angles and for different concentration of micro emulsion droplets. The intensity of scattering radiation is measured as a function of the scattering vector q, Q= (4ᴫ/λ) sinƟ/2 Where Ɵ is the scattering angle λ is the wave length of the radiation  These methods are use to obtain quantitative informations on the size, shape and dynamics of the components.

19. Nuclear Magnetic Resonance Studies: Structure and dynamics of micro emulsion.  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.

20. 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.

21. 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 .

22. 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

23. Oral Drug Delivery: ►Micro emulsions extensively studied for protection of biodegradable drugs. ► Short half-life, stability, biodegradability of these molecules cause considerable design difficulties in their formulation for oral administration.

24. 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.

25. Topical drug delivery: ► Transdermal drug delivery system exhibits several advantages than oral route, by avoiding systemic side effects. ► Lecithin containing w/o micro emulsion of scopolamine and broxaterol was used for the transdermal administration and found that the transport rate obtained with the lecithin micro emulsion gel was much higher than that obtained with an aqueous solution at the same concentration. Example:

26. Parenteral Administration: ► In order to attain prolonged release and to administer parenterally lipophilic substances that are not soluble in water, o/w micro emulsion may be used as carriers. ►They can be administrated by intravenous, intramuscular, subcutaneous route. The potential of o/w micro emulsions 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

27. 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

28. “ Multiple emulsions are novel drug delivery systems, in which the dispersed phase contain smaller droplets that have the same composition as the external phase”. They also called as “ double emulsion systems /liquid membrane systems MULTIPLE EMULSION

29. TYPES OF MULTIPLE EMULSIONS: a)oil-in-water-in oil (O/W/O) emulsion system b)water-in-oil-in water (W/O/W) emulsion system (a) W/O/W double emulsion (b) O/W/O double emulsion 37

30. PRINCIPLES OF LIQUID SURFACTANT MEMBRANE EMULSIONS In W/O/W emulsion ,2 miscible aqueous phases separated by organic phase is called liquid membrane. It is composed of hydrocarbon solvent, emulsifier, additives. It must satisfy 2 primary requirements: It must have ability to form stable emulsion It must have negligible effect on drug activity 38

31. METHODS OF PREPARATION Two step emulsification(double emulsification): 39

32. Modified two step emulsification technique: The composition of internal aqueous phase –oily phase –external phase is fixed at 1:4:5 to produce stable W/O/W emulsion. 40

33. Phase inversion technique (one step technique): 41

34. mechanical equipments used for emulsification process a)laboratory scale homogenizer b)colloidal mill c)ultra sonifier d)large scale homogenizer used in industries

35. METHODS TO STABILIZE MULTIPLE EMULSIONS Liquid crystal stabilized multiple emulsion Stabilization in presence of electrolytes Stabilization by forming polymeric gel Stabilization by interfacial complexation between non-ionic surfactant and macromolecules Phase-inversion stabilization of W/O/W emulsion 43

36. APPLICATIONS IN THERAPEUTICS AND COSMETICS Controlled and sustained drug delivery of various drugs Targeting of bioactives Vaccine adjuvants Multiple emulsions for local immuno suppression Enhancement of absorption Delivery of proteins and peptides Haemoglobin multiple emulsion for oxygen delivery Enzyme immobilization 44

37. Conclusion Micro emulsion 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 micro emulsion properties are beginning to be satisfactorily understood, especially the droplet structure, large research domains remain to be clarified. With evaluation of newer techniques of preparation, stabilization, rheological properties can serves as potential carrier for drugs ,cosmetics ,pharmaceutical agents

38. REFERENCES S.P. Vyas , R.K. Khar. Targeted & Controlled drug delivery: novel carrier systems , 1 st ed. New Delhi: CBS publishers ; 2004,page no 303-303 Micro emulsions as drug delivery system,A.N Lalwani,T.J shah&N.S Parmar-309 Targeted &Controlled Drug delivery vyas/khar-303 Progress in controlled and novel drug delivery system- nk jain Advance in controlled &drug delivery A.j khapae&N.K jain-381

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