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Methods of preparation of novel emulsion
- 1. Methods of Preparation ofNovel Emulsion 1 Presented By Manali Parab M.Pharmacy Ist year (Sem Ist) Pharmaceutics Department
- 2. Emulsion Emulsion canbe defined as heterogeneous system where one immiscible liquid is dispersed in another in the form of droplets and stabilized by third component called emulsifying agent These have been described as heterogeneous systems of one immiscible liquid dispersed in another in the form of droplets, which usually have diameters greater than 1 μm . Types of emulsion Oil in water (o/w) Water in oil (w/o) 2
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- 4. MULTIPLE EMULSION Multipleemulsions are more complex systems as the drops of the dispersed phase themselves contain even smaller dispersed droplets which normally consist of a liquid which is miscible, and in most cases, is identical with the continuous phase. They are therefore, emulsions of emulsions. For each type of multiple emulsion, the internal and external phases are alike and an intermediate phase separates the two like phases. The intermediate phase is immiscible with the two like phases. An emulsifier is present to stabilize the emulsion and a variety of ionic and non-ionic surfactants are available for this purpose. Lipophilic (oil-soluble, low HLB) surfactants are used to stabilize W/O emulsions, whereas hydrophilic (water-soluble, high HLB) surfactants are used to stabilize oil/water systems. 4
- 5. The oillayer acts as a membrane separating these two aqueous phases. Polar molecules dissolved in either the internal aqueous phase or the external continuous aqueous phase can pass through the oil layer by diffusion because of the concentration gradient. In the case of water this is driven by osmotic pressure. Molecules are often transported via micelles of hydrophobic surfactant present in the oil phase. Water diffusion causes swelling, bursting, or shrinkage of the internal aqueous droplets, affecting the stability of the multiple droplets as well as the release profiles of the active ingredients loaded in the inner dispersed aqueous phase For eg. Valsartan multiple emulsion 5
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- 7. Method of preparation Two step emulsification Phase inversion technique Membrane emulsification 7
- 8. Two step emulsification Complexsystem Liquid membrane system Thermodynami cally stable Low HLB added to Oily phase Low HLB: Hydrophobic High HLB: hydrophobic Require two emulsifier Multiple emulsion 8
- 9. Multiple emulsion w/o/wcontains two types of emulsifier Low HLB surfactants ( hydrophobic in nature) High HLB surfactants ( hydrophilic in nature) Low HLB surfactants are used in dispersed phase High HLB surfactants are used in continuous phase 9
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- 12. Phase inversion technique/ onestep emulsification 12 Oil +lipophilic surfactant aqueous solution + hydrophillic emulsifier migration of the emulsifier between phases concentration of dispersed globules in dispersion medium is quite high i.e., globules are packed very closely in suspending fluid. w/o/w emulsion
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- 14. Membrane emulsification technique Inthis method, a w/o emulsion (a dispersed phase) is extruded into an external aqueous phase (continuous phase) with a constant pressure though a porous glass membrane. The particle size can be controlled by controlling size of porous glass membrane. Porous glass used is Shirasu porous glass given by SPG technology Miyazaki, Japan 14
- 15. The relation betweenmembrane pore size and particle size of emulsion exhibits good correlation as described by the formula: Y= 5.03X + 0.19 Where, X= the pore size Y= the mean particle size A micro porous glass membrane with narrow pore size range was used successfully for preparing stable simple (o/w) and water-oil-water (w/o/w) type emulsion 15
- 16. Cross-Flow Membrane Emulsification To preparemonodisperse emulsion using a particular glass membrane called Shirasu Porous Glass (SPG) membrane (SPG Technology, Miyazaki, Japan) In cross-flow membrane emulsification, the dispersed phase is pressed through a microporous membrane (micropore diameter is dp) while the continuous phase flows along the membrane surface. Droplets grow at micropores and detach at a certain size (dd), which is determined by the balance between the forces acting on the droplet. Emulsifiers in the continuous phase stabilize the newly formed inter-face, to prevent droplet coalescence immediately after formation. 16
- 17. DISADVANTAGES Direct membrane emulsification(DME). There are some potential disadvantages with this technique (i) the relatively low maximum dispersed phase flux (typically 0.01–0.1m3 /(m2 h)) that leads to low productivity; (ii) it is difficult to prepare uniform emulsion droplets when the dispersed phase has high viscosity . 17
- 18. (iii) Uniformemulsion can only be prepared using a microporous membrane with very uniform pores. Because of these restricted conditions, there have been some limitations in choosing the dispersed phase, the continuous phase, and the membrane to obtain the desired emulsification products 18
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- 21. Microemulsion ultra low interfacial tension Mixtureof Surfactants & cosurfactant transparent or nearly transparent Microemulsion 21
- 22. Three types ofmicroemulsion are likely to be formed O/W microemulsion W/O microemulsion Bicontinuous microemulsion 22
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- 25. Formulation Microemulsion formulationis specific to the nature of oil/surfactant pair, surfactant concentration and the oil/surfactant ratio, the concentration and nature of co- surfactant and surfactant/co-surfactant ratio and the temperature. Hence main components of microemulsion system are as follows Oil phase Primary surfactant Secondary surfactant (co-surfactnt) Co-solvent 25
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- 27. Methods of formulationof microemulsion Phase titration method (water titration method) Microemulsion are prepared by spontaneous emulsification method (phase titration method) and can be depicted using phase diagrams. Microemulsion formed with several association structures (emulsion, micelles, various gels and oily dispersions) depending on chemical composition and concentration of various substances As quaternary phase diagram is difficult to interpret, pseudo ternary diagrams are constructed to find out different zones, in each corner of the diagram represents 100% of each component 27
- 28. Ternary phase diagrams Numberof intermediate structural phases, including bicontinuous, lamellar, hexagonal and multiple phases, when a mixture of surfactant and oil at certain ratios is mixed gradually with water. Bicontinuous structure may exist in systems where the amount of water and oil are similar and both oil and water exist as a continuous phase Multiple phases may exist where there is insufficient surfactant to form a single microemulsion phase, particularly for compositions close to the oil-water binary axis The transitions between the various phases mapped out in the phase diagram can be driven by changing the temperature or addition of a component 28
- 29. Preparation of samplesfor analysis and construction of phase diagrams 1. One is titration of a mixture of two components with the third component, for example, using water to titrate the mixture of surfactant and oil. 2. The other is preparation of a large number of samples with different compositions (i.e. different ratios of three components) In order to speed up the process, heat and sonication are often employed in the experimentation 29
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- 32. Emulsion titration/dilution method Thismethod involves a two step process in which a premade nonionic surfactant stabilized (e.g. Tween 80) o/w conventional emulsion is diluted into an aqueous surfactant micellar solution (e.g. 1% Tween 80) This method can thus be called ‘emulsion titration or dilution method’, however, this method involves both high energy and low energy methods Formation of microemulsions by the emulsion dilution method was shown to be highly dependent on the concentration of oil in the final mixture. This means that the level of oil concentration required to be diluted into the surfactant solution to enable to form microemulsions (e.g., oil droplet size smaller than 50 or 100 microm) is limited and determined by the amount of titrated conventional emulsion into a surfactant solution This method has also been called “oil exchange”, “swelling of o/w emulsion”, “oil solubilisation” or “molecular transport” 32
- 33. It was shownthat the size of oil droplets smaller than 100 nm could be formed by this approach only when a oil concentration added was lower than 1.5 wt% oil in the final mixture When the volume of emulsion added has a relatively low concentration of oil droplets, all of the oil molecules in the emulsion move out of the droplets and are incorporated into the surfactant micelles. several possible mechanisms (1) oil molecules are directly solubilized in water, and then they are accommodated by micelles in the aqueous phase; (2) oil molecules are incorporated into micelles due to the collision of micelles with the surface of emulsion droplets; 33
- 34. DISADVANTAGES Certain typesof emulsifiers can be used which are limited to mostly nonionic small molecule surfactants Certain types of low viscosity and non triglyceride oils, and the level of oil concentration should be low 34
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- 39. Nanoemulsion Nanoemulsion canbe defined as oil in water emulsion with mean droplets diameters ranging from 50 to 100nm. It is also called as sub micron emulsion or mini emulsion These are group of dispersed particles used for pharmaceutical and biomedical aids and vehicles that show great promise for cosmetics, diagnosis, drug therapies and bio technologies. Due to their small droplet size Nanoemulsions possesses stability against sedimentation or creaming with Ostwald forming main mechanism Nanoemulsions breakdown. 39
- 40. Methods of formulationof nanoemulsion High pressure homogenization In high pressure homogenizer, the dispersion of two liquids (oily phase and aqueous phase) is achieved by forcing their mixture through small inlet orifice at very high pressure (500 to 20000psi), which sublet the product to intense turbulence and hydraulic shear resulting in extremely fine particles of emulsion. 40
- 41. Aqueous phase+ oleaginousphase (heated and pH adjustment) heated and filtration 41 Add emulsifying agent Rapid cooling High pressure homogenizer (500 to 20000psi) Formation of droplets of very small size
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- 43. Microfluidization Microfluidic technologiesare indicated to manipulate small quantities of liquids or fluids usually through channels with at least one dimension smaller than 1 mm, for emulsion formation, mixing and dispersion. Microfluidizer high shear fluid processors are unique in their ability to achieve uniform particle size reduction, bottom-up crystallization and efficient cell disruption. Product enters the system via the inlet reservoir and is powered by a high-pressure pump into the interaction chamber at speeds up to 400 m/s. 43
- 44. An interactionchamber where two channels of fluid flow at high velocity and collide with each other When the fluids from the two channels collide, it generates intense, disruptive forces that result in very small emulsion droplets. It is then effectively cooled, if required, and collected in the output reservoir. The exclusive fixed-geometry interaction chambers combines with a constant pressure pumping system to produce unparalleled results 44
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- 47. Ultrasound emulsification Inthis method, a probe emits ultrasonic waves (20kHz) to disintegrate microemulsion by means of cavitation forces. In the dispersing zone, imploding cavitation bubbles cause intensive shock waves in the surrounding liquid and result in the formation of liquid jets of high liquid velocity. n order to stabilize the newly formed droplets of the disperse phase against coalescence, emulsifiers (surface active substances, surfactants) and stabilizers are added to the emulsion. 47
- 48. As coalescenceof the droplets after disruption influences the final droplet size distribution, efficiently stabilizing emulsifiers are used to maintain the final droplet size distribution at a level that is equal to the distribution immediately after the droplet disruption in the ultrasonic dispersing zone. By varying ultrasound energy input and time, the nanoemulsion of desired properties can be obtained. Undesirable for thermolabile drugs and macromolecues (retinoids, proteins, enzymes and nucleic acids) 48
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- 53. http://www.ijddr.in/drug- development/preparation-and- optimization-of-nanoemulsions-for- targeting-drugdelivery.php?aid=5740 http://www.slideshare.net/MUHEEM_007/ nanoemulsion Vesicular and Particulate Drug Delivery System by Prof. R.S.R. Murthy Controlled and Novel Drug Delivery N.K. Jain CBS Publishers & Distributors 53
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Editor's Notes
- #22 20 - 500 Å, and so is much smaller than the wavelength of light (4000 Å ≤ l light ≤ 7000 Å). Hence, microemulsions are generally weak scatterers of light, and this explains their transparency.