Pharmaceutics I - Pharmaceutical Emulsions PDF

Pharmaceutics I Pharmaceutical Emulsions Prof. Dr. Gamal Zayed Prof. of Pharmaceutics and Pharmaceutical Technology  Definition Types Differences between different types of emulsion Way of detecting emulsion types Application Factors affecting emulsification Emulsifying...

Pharmaceutics I Pharmaceutical Emulsions Prof. Dr. Gamal Zayed Prof. of Pharmaceutics and Pharmaceutical Technology  Definition Types Differences between different types of emulsion Way of detecting emulsion types Application Factors affecting emulsification Emulsifying agents (definition, ideal characteristics, classification)  Outlines Introduction Theoretical Aspects Types and Applications Emulsion Stability Formulation of Emulsion Properties of Emulsion and Emulsifiers  Introduction Def. 1: Emulsions are a class of disperse systems consisting of two immiscible liquids, one of which is dispersed as globules (dispersed phase = internal phase) in the other liquid (continuous phase = external phase) that is stabilized by an emulsifying agent. OR Def. 2: An emulsion is a thermodynamically unstable system consisting of at least two immiscible liquid phases one of which is dispersed as globules in the other liquid phase stabilized by a third substance called emulsifying agent. It consists of a two-phase system prepared by combining two immiscible liquids, one of which is dispersed uniformly throughout the other. Internal phase = the dispersed phase, External phase or dispersion medium = continuous phase.  The liquid that is dispersed into small droplets is called the dispersed phase or internal phase or discontinuous phase The other liquid is the dispersion medium Internal phase Continuous phase A. Two immiscible liquids, not emulsified. B. An emulsion of Phase B dispersed in Phase A. C. The unstable emulsion regressively separates. D. The surfactant positions itself on the interfaces between Phase A and Phase B, stabilizing the emulsion. Examples of Pharmaceutical Emulsions: 1) Lotions 2) Liniments 3) Creams 4) Ointments 5) Vitamin drops Calssification (Types) of emulsion: 1- Simple emulsions/Macroemulsions containing one internal phase. oil-in-water emulsion (o/w) water-in-oil emulsion (w/o) Macroemulsion: Droplets size range approximately 5 mm 2- Multiple-emulsion: it contains two internal phases. oil in water in oil (o/w/o) water in oil in water (w/o/w) Multiple emulsions can be used to delay release or to increase the stability of the active compounds. 3- Microemulsions : They may be def ined as dispersions of insoluble liquids in a second liquid that appears clear and homogenous to the naked eye. They are clear, stable, liquid mixtures of oil, water and surfactant (e.g ionic surfactant such as sodium stearate), frequently in combination with a co-surfactant. In contrast to ordinary emulsion, microemulsions form upon simple mixing of the components and do not require the high shear conditions generally used in the formation of ordinary emulsions. The two basic types of microemulsions are (o/w) and (w/o). Different types of emulsions (O/W, W/O and multiple emulsions O/W/O and W/O/W)  When oil is the dispersed phase and an aqueous solution is the continuous phase, the system is designated as an oil-in -water (O/W) emulsion. Conversely, where water or an aqueous solution is the dispersed phase and oil or oleaginous material is the continuous phase, the system is designated as water-in-oil (W/O) emulsion. Water-in-oil (W/O) emulsion used for intramuscular injections for a depot effect (extended release or long acting effect).  Oil-in-water (O/W) emulsion used for oral and intravenous administration. 20 mL ampule of 1% propofol emulsion suitable for intravenous injection. Advantages of emulsions over other liquid forms 1- The unpleasant taste or odor of an oil can be masked par tially or wholly, by emulsif ic ation. Pharmaceutical emulsions may be used to mask the bitter taste and odor of drugs, in which the drug is dissolved in the internal phase of an o / w e mul si o n. The e x t e rnal phase may t he n be formulated to contain the appropriate sweetening and flavoring agents. 2- Pharmaceutical emulsions may be used to deliver drugs that are poorly soluble in water but readily soluble in oils. E.g., in oil-in-water emulsions the drug substance is dissolved in the discontinuous or internal oil phase. 3- The stability of many drugs which are unstable in aqueous solutions is increased when incorporated into an emulsion 4- Prolonged drug action and increased bioavailability are often obtained when drugs are incorporated into emulsions. 5- Drugs that are more stable in an oily phase compared to an aqueous medium can show improved stability in an emulsion dosage form. Emulsions provide protection to drugs which are susceptible to oxidation or hydrolysis. 6- Emulsions are used widely to formulate externally used products like lotions, creams, liniments etc. The appearance of oleaginous materials intended for topical applications is usually improved when formulated in an emulsified form.  Why would you want an o/w emulsion instead of a w/o emulsion for an oral dosage form? palatable to the mouth and the liquid consistency would be easier to flow through the mouth and down the throat. The continuous water phase would be more smelling drug in the oil phase, your taste buds and your sense of smell will be unaware of the agent passing by. By dispersing a foul tasting or taste buds as the medication passes over them. the manufacturer can add sweeteners and flavors to the continuous phase which will be experienced by the In addition, in the o/w emulsion  Disadvantages of Emulsion 1- Complex process – Creating an emulsion can be a complex and dif fic ult process, requiring specif ic equipment and techniques to properly mix and stabilize the liquids. 2- Limited shelf life – Emulsions can have a limited shelf life, as the stability of the mixture can be affected by temperature, pH, and other factors, leading to separation or spoilage. 3- Sensitive to temperature changes – Emulsions can be sensitive to temperature changes, and may separate or break down if exposed to extreme heat or cold. 4- Dif fic ult to reverse – Once an emulsion is created, it can be difficult to reverse the process and separate the original liquids. 5- Can be unstable – Emulsions can be unstable and can easily break down, which can lead to separation and the loss of the desired properties of the emulsion. Pharmaceutical emulsions are thermodynamically unstable and therefore must be formulated to stabilize the emulsion from separation of the two phases. 6- Bulky, d if fic ult to transpor t, and prone to c ontainer breakages. 5- Liable to microbial contamination which can lead to cracking. 6- Uniform and accurate dose my not be achieved. - Preparation needs to be shaken well before use - A measuring device is needed for administration - A degree of technical accuracy is needed to measure a dose Mechanism of Emulsion Formation (Emulsification) Blending of a small amount of oil and water results in a two phase system because “water and oil do not mix”. If the same small amount of oil is added to an aqueous solution of a suitable surfactant in the micellar state, the oil may preferentially dissolve in the interior of the micelle because of its hydrophobic nature. A number of different chemical and physical processes and mec hanisms c an be inv o lv ed in the pro c ess o f emulsification. 1- S u r f a c e t e n s i o n t h e o r y : A c c o r d i n g t o t h i s t h e o r y, emulsification takes place by the reduction of interfacial tension between two phases 2- Repulsion theory: The theory proposes that the emulsifying agent creates a f il m over one phase that forms globules, which repel each other. This repulsive force causes them to remain suspended in the dispersion medium. 3- Viscosity modification: Certain emulgents (emulsifying agents) such as acacia, tragacanth, carboxymethylcellulose, polyethylene glycol, etc increase the viscosity of the medium, which helps create and maintain the suspension of globules of the dispersed phase 4- Multiple Emulsion Method: Multiphase emulsions are prepared by the solvent evaporation technique by a three-step emulsification process. A) Aqueous drug solution and oil phase containing emulsion stabilizers are combined to give a water-in-oil emulsion (step 1). Later the w/o emulsion is dispersed in the polymer solution (step 2). The solvent is evaporated under reduced pressure (step 3). B) In other way: preparation of a primary o/w emulsion in which the ‘oily dispersed phase’ in an organic solution of the drug and the ‘aqueous continuous phase’ is an aqueous solution containing chitosan and an emulsifier (step 1); multiple emulsion formation with a ‘oily outer phase’ (step 2); and finally, cross-linkage adding a cross-linking agent (step 3). Hint: Hydrophobic drugs are prepared using o/w/o multiple emulsion method. Hydrophilic drugs are prepared using w/o/w multiple emulsion method.  Emulsions tend to have a cloudy appearance, because the many phase interfaces (the boundary between the phases is called the interface) scatter light that passes through the emulsion. Em ul si ons are unstab l e and thus d o not f orm spontaneously. Energy input through shaking, stirring, homogenization, or spray processes are needed to form an emulsion. Over time, emulsions tend to revert to the stable state of oil separated from water. Surface active substances (surfactants) can greatly increase the kinetic stability of emulsions so that, o nc e f o rm e d , t he e m ul si o n d o e s no t c ha ng e significantly over years of storage.  Emulsions are unstable because: The globules of the dispersed liquid tend to coalesce (combine) to form large globules until all of the dispersed globules have coalesced. An emulsifying agent is usually added to the system to prevent the coalescence (combination) of the dispersed globules and maintain the integrity of the individual globules of the dispersed phase. An emulsion of two liquids without a stabilizer will quickly separate back to the original state of two separate liquid layers, a phenomenon known as breaking or cracking. This state is approached via several distinct processes, some of which are reversible such as f locculation and creaming and or irreversible process such as coalescence.  Emulsion Stability (Instability) The term emulsion stability refers to the ability of an emulsion to resist changes in the properties over time. An emulsion is said to be stable, if it remain as such after its preparation i.e. the dispersed globules are uniformly distributed throughout the dispersed medium during its storage. The more stable the emulsion, the more slowly its properties change, An emulsion is said to be unstable, if the internal phase is separated from the external (continuous) phase and the emulsion is described being cracked or broken. Instability of emulsion can be 1- Physical instability 2- Chemical instability  An emulsion is considered physically unstable if: -The internal phase tends to form globule aggregates -Large globules rise to the top (cream) or fall to the bottom to form a concentrated layer of emulsified internal phase globules -If the emulsion breaks (coalescence of the internal phase globules into a distinct phase).  Emulsion Stability What causes an emulsion to break? The globules coalesce due to too little emulsifying agent in the first place or possibly due to degradation of the emulsifying agents by chemical or enzymatic (from microbes or other sources) means. Sterility isn't necessary with oral emulsions, but destruction of the microbes can improve the physical stability of emulsion formulations. Fungistatic preservatives are generally included because fungi (molds and yeasts) are more likely to contaminate emulsions than are bacteria.  Emulsion Stability What causes an emulsion to break? Methylparaben and propylparaben are frequently used to serve this function. Alcohol at 12-15%, based on the aq ue o us v o lume , is fre q ue ntly ad d e d to o ral o /w emulsions for preservation. Care must be taken to protect emulsions against extremes of cold and heat. Freezing and thawing causes a coarsening of an emulsion and sometimes causes breaking. Excessive heat has the same effect. Light-resistant containers which can seal tightly should be used to protect the emulsion from photolysis and oxidation. Chemical antioxidants are usually employed.  Emulsion Stability In light of these considerations, the physical instability of pharmaceutical emulsions may be classified as follows: 1. Flocculation 2. Coalescence or Aggregation 3. Creaming or sedimentation 4. Cracking or Breaking 5. Phase inversion  Emulsion Stability I- Flocculation : Flocculation is def ined as a weak reversible association or aggregation of emulsion droplets which are separated by trapped continuous phase. However these aggregates can easily be redispersed upon shaking. Flocculation is differentiated from coalescence primarily by the fact that the interfacial thin f il m which composed of continuous phase and adsorbed emulsif ier remains intact and that aggregation may be reserved. However these aggregates can easily be redispersed upon shaking (reversible). It is considered as a precursor to the irreversible coalescence. It differs from coalescence mainly in that interfacial f il m and individual droplets remain intact (separated from each other).  Flocculation is inf lu enced by the charges on the surface of the emulsif ie d globules. The reversibility of f lo cculated emulsion depends upon strength of interaction between particles as determined by: A. The chemical nature of emulsifier, B. The phase volume ratio, C. The concentration of dissolved substances, specially electrolytes and ionic emulsifiers.  Emulsion Stability II- Coalescence : While f locculation (aggregation) is the clumping together of particles, coalescence is the fusing of the agglomerates into a large drop or drops. Definition: It is the process in which the dispersed phase droplets join/merge to form larger particles and the emulsion generally cannot be recovered by simple agitation Coalescence is usually rapid when two Immiscible liquids are shaken together, since there is no large energy barrier to prevent fusion of drops or reformation of the original bulk phases. If no protective barrier is present at the interface, or if very low surface coverage by emulsif ie r exists, emulsion droplets rapidly aggregate and coalesce.  Emulsion Stability Flocculation and Coalescence : When an emulsifying agent is added to the system, f lo cculation still may occur but coalescence is reduced to an extent depending on the ef fic acy of the emulsifying agent to form a stable, coherent interfacial film. It is therefore possible to prepare emulsions that are flocculated, yet which do not coalesce. What are the differences between Flocculation and Coalescence?  Emulsion Stability III- Creaming and sedmentation The upward or down ward movement of dispersed droplets (Internal Phase) is termed creaming or sedimentation respectively. Creaming or sedimentation occurs when the dispersed droplets or f loccules separate under the inf luence of gravity to form a layer of more concentrated emulsion, the cream. Creaming may be def ined as the upward movement of dispersed globules to form a thick layer at the surface of the emulsion. Creaming is temporary phase because it can be re- distributed mild shaking or stirring to get again a homogenous emulsion. As far as possible creaming of an emulsion should be avoided because it may leads to cracking with complete separation of two phases.  In any emulsion, creaming or sedimentation takes place depending on the densities of disperse and continuous phases. Generally a creamed emulsion can be restored to its original state by gentle agitation. Most oils are less dense than water so the oil droplets in an o/w emulsion rise to the surface to form an upper layer of cream. In w/o emulsions, the cream results from the sedimentation of water droplets and forms the lower layer. Factors affecting rate of creaming: Rate of creaming is governed by Stoke’s law. As per Stoke’s law V = 2r 2(ρ1- ρ2 )g / 9η Where: V = rate of creaming or sedimentation r = radius of droplets of dispersed phase ρ1, ρ2 = density of dispersed and continuous phase respectively g = gravitational rate constant η = viscosity of continuous phase. 1- Droplet size: A s pe r St o ke’s l a w, ra t e o f c re a m i ng i s d i re c t l y proportional to the square of radius or diameter of the droplet size. Smaller is the diameter of the droplet, lesser will be the rate of creaming. So reduction in droplet size by using a homogenizer helps in reducing creaming or sedimentation. 2- Difference in densities of dispersed and continuous phase: According to Stoke’s law no creaming is possible if densities of the two phases are equal. So Creaming can be avoided by adjusting the density of dispersed phase. 3- Viscosity of the continuous phase: The rate of creaming is inversely proportional to viscosity of the continuous phase. So increase in viscosity of the continuous phase by adding thickening agents can reduce the rate of creaming. Factor affecting viscosity of emulsions: A)Viscosity of continuous phase: Is directly proportional to the viscosity of continuous phase. -Clays and gums increase the viscosity of continuous phase. -For w/o emulsions addition of polyvalent metal soaps or use of high melting waxes and resins in the oil phase can be used to increase the viscosity. B) Volume of internal phase: Depends upon the volume of internal phase. More the volume of internal phase greater is the viscosity. C) Particle size of dispersed phase: On the particle size of dispersed phase. Smaller the globule size, more will be the viscosity. That is why emulsion stability can be improved by reduction in globule size. 4- Storage condition: Rate of creaming is also depended on the temperature of storage condition.  Emulsion Stability (…cont.) Creaming and Stokes’ Law Analysis of the equation shows that if the dispersed phase is less dense than the continuous phase, which is generally the case in the o/w emulsions, the velocity of sedimentation becomes negative, that is, an upward Creaming results. If the internal phase is heavier than the external phase, the globules settle, a phenomenon customarily noted in w/o emulsions in which the internal aqueous phase is more dense than the continuous oil phase. This effect may be referred to as creaming in a downward direction (Sedmenattion). The diameter of globules is seen IV- Phase Inversion: It mean the change of one type of emulsion into the other type. i.e. oil in water (o/w) emulsion changes into water in oil (w/o) type and vice versa. Phase inversion is a physical instability. It may be brought about by: 1- the addition of an electrolyte e.g. addition of CaCl2 into o/w emulsion formed by sodium stearate can be inverted to w/o. 2- by changing the phase volume ratio 3- by temperature changes. Phase inversion can be minimized by: 1- U s i n g t h e pr o pe r e m u l s i f y i n g a ge n t i n a d e q u a t e concentration 2- Keeping the concentration of dispersed phase between 30 to 60 % 3- Storing the emulsion in a cool place. V- Cracking or Breaking: An emulsion of two liquids without a stabilizer will quickly separate back to the original state of two separate liquid layers, a phenomenon known as breaking or cracking. This state is approached via several distinct processes, some of which are reversible such as f locculation and creaming and or irreversible process such as coalescence.  External factors can also lead to breakdown of the emulsion I- Temperature A)Alters emulsifier solubility B)Nonionics become less water-soluble with increasing temperature C)Anionics become more water soluble with increasing temperature D)HLB effectively decreases with increasing temperature, when the emulsifier system is solely nonionic E)Surfactant moves away from oil/water interface thus destabilising emulsion II- Water quality A)Presence of electrolytes impact on surfactant solubility B)Salting out solutes include NaOH, CaCO3, MgSO4 C)Certain anionics interact with hard water D)Solubility changes cause interface partitioning changes E)Anionic/nonionic systems resistant to hard water Methods to increase the emulsion stability Each of the individual causes of emulsion breakdown can be controlled by formulation technique and surfactant selection. Some corrections are easy to implement, some require a radical reformulation of the emulsion system Reduce Creaming and Sedimentation by: 1- Density adjustment - type of solvent or oil in disperse phase 2- Lower mean particle size of the disperse phase - mode of formation of the emulsion 3- Increase viscosity of the continuous phase - addition of protec tive c olloid s, attention to struc ture of surfac tant hydrophobe
Reduce Flocculation by: 1- Increasing surfactant concentration 2- Reinfo rc e the entro pic barrier- no nio nic /po lymeric surfactant species 3- Reinforce the electrostatic barrier - ionic surfactant species Reduce Coalescence by: 1- Prevention of creaming 2- Increase the interfacial film thickness and elasticity 3- Use of polymeric stabilizers Reduce Phase Inversion by: 1- Review and revise phase ratio 2- Increase phase inversion temperature 3- Review ionic/nonionic ratio 4- Increase EO number of nonionic component 5- Decrease carbon number of hydrophobe  Emulsifying Agents  Emulsifying Agents are the substances added to an em ulsion to prev ent the c oalesc enc e of the globules of the dispersed phase.  They are also known as emulgents or emulsifiers.  They ac t by reduc ing the interfac ial tension between the two phases and forming a stable interfacial film.  The choice of selection of emulsifying agent plays a very important role in the formulation of a stable emulsion.  No single emulsifying agent possesses all the properties required for the formulation of a stable emulsion therefore sometimes blends of emulsifying agents have to be taken. Emulsifier: An emulsif ie r (or surfactant) is a substance which stabilizes an emulsion. Detergents are another class of surfactant, and will chemically interact with both oil and water, thus stabilizing the interface between oil or water droplets in suspension. This principle is exploited in soap to remove grease for the purpose of cleaning. A wide variety of emulsif ie rs are used in pharmacy to prepare emulsions such as creams and lotions. The effectiveness of the emulsifying agent depends on its chemical structure, concentration, solubility, pH, physical properties and electrostatic effect.  Criteria For The Selection of Emulsifying Agents : An ideal emulsifying agent should posses the following characteristics: It should be able to reduce the interfacial tension between the two immiscible liquids. It should be physically and chemically stable, inert and compatible with the other ingredients of the formulation. It should be non irritant and non toxic in the conc., used. It should be organoleptically inert i.e. should not impart any color, odour or taste to the preparation. It should be able to produce and maintain the required viscosity of the preparation. It should be able to form a coherent f il m around the globules of the dispersed phase and should prevent the coalescence of the droplet of the dispersed phase Emulsifier Selection The selection of emulsifier is based on Required emulsion type, i.e O/W, W/O, W/O/W Nature of the oil phase, ie. polar, non-polar R e g u l a t o r y r e s t r i c t i o n s , i e. F o o d a p p r o v e d , b i o d e g r a d a b i l i t y
Other factors to consider The chemical “affinity” between surfactant hydrophobe and oil phase Blends of surfactants are more effective than single emulsif ie r of correct HLB Blends of anionics and nonionics can be more effective than either type alone The possibility of chemical reaction between the emulsif ie rs and the oil phase, solutes in the oil phase, or solutes in the aqueous phase  Desired features of emulsifier It must be compatible with the other components in the formulation, which means it must not interfere with the chemical stability of each of the components or with the therapeutic efficacy of the drug. It must be stable in the preparation itself. If it decomposes or degrades, what good is it? The agent must be nontoxic. It should not possess an unacceptable odor, taste or color. It must assist in the formation of and continue to support the emulsified system throughout the shelf-life of the product. The cost of emulsifiers  Desired features of emulsifier Emulsifying agents, in general, assist in the formation of emulsion by three mechanisms: A. Reduction of interfacial tension (thermodynamic stabilization). B. Formation of a rigid interfacial f ilm (mechanical barrier to coalescence). C. Formation of an electrical double layer (electrical barrier to approach of particles).  Types of emulsifier 1- Carbohydrates: Naturally occurring agents obtained from vegetable sources such as acacia, Tragacanth, agar, and pectin. Theses substances are of variable chemical composition, so they exhibit a considerable variation in their emulsifying properties. Since carbohydrate acts as good media for the growth of microorganisms, therefore emulsion prepared using these emulsifying agents have to be preserved to prevent the of growth of microorganisms. These agents generally help to produce o/w emulsions because they are water soluble Acacia is an acidic polysaccharide and it is probably the most common emulsifier for preparations..  Types of emulsifier 2- Macromolecules such as proteins: Naturally occurring agents such as gelatin, egg white and c ase i n, w hi c h al so he l p t o p ro d uc e o / w emulsions. They are not very popular since they form thin emulsions, but more importantly because they decom pose rapidly which results in a broken emulsion.  Types of emulsifier 3- Semi-synthetic polysaccharides: Include mainly cellulose derivatives Such as sodium carboxymethyl cellulose, hydroxy propyl methyl cellulose and methyl cellulose. They are used for formulating o/w emulsion and acts by increasing the viscosity of the system 4- Surface active agent Surfactants: They are adsorbed at the oil/water interface to form monomolecular f il m to reduce the interfacial tension. This group contains surface active agents which act by getting adsorbed at the oil water interface in such a way that the hydrophilic polar groups are oriented towards water and lipophillic non polar groups are oriented towards oil, thus forming a stable f ilm. This f il m acts as a mechanical barrier and prevents coalescence of the globules of the dispersed phase. The functions of surface active agents to provide stability to dispersed droplets are as following: i. Reduction of the interfacial tension ii. Form coherent monolayer to prevent the coalescence of two droplet when they approach each other iii.Provide surface charge which cause repulsion between adjacent particles Surface active agent (SAA) is molecule which have two parts, one is hydrophilic and the other is hydrophobic. Upon the addition of SAA, they tend to form monolayer film at the oil/water interface. Combination of surface-active agents is used most frequently. The combination should form film that closely packed and condensed. H y d r op h i l i c W ater h ead H y d r op h ob i c tai l O il  Classification of surface active agents (surfactants): They are classified according to the ionic charge possessed by the molecules of the surfactant e.g., anionic, cationic, non-ionic and ampholytic. i.Anionic Surfactants: In aqueous solutions these compounds dissociate to form negatively charged anions that are responsible for their emulsifying ability. The long anion chain on dissociation imparts surface activity, while the cation is inactive. T h e se a ge n t s a r e pr i m a r i l y u se d f o r e x t e r n a l preparations and not for internal use as they have an unpleasant bitter taste and irritant action on the intestinal mucosa. e.g., alkali soaps, polyvalent soaps (metallic soaps), organic soaps, sulfated and sulphonated compounds. ii. Cationic Surfactants: In aqueous solutions, these compounds dissociate to form positively charged cations that provide the emulsifying properties. They are mainly used in external preparations such as lotions and creams. Quaternary ammonium compounds such a s c e t r i m i d e ( c e t y l t r i m e t h y l a m m o n i u m br o m i d e ) , benzalkonium chloride and benzethonium chloride are examples of important cationic surfactants. These compounds besides having good antibacterial activity are also used in combination with secondary emulsifying agents to produce o/w emulsions for external application. Example: Quaternary ammonium compounds (cetyl trimethyl ammonium bromide) CH3(CH2)14 CH2N+ (CH3)3 Br- iii). Nonionic surfactants: Nonionic surfactants are undissociated surfactants. They are the class of surfactants widely used as emulsifying agents. They are extensively used to produce both o/w and w/o emulsions for internal as well as external use. These products range from oil-soluble compounds stabilizing w/o emulsions to water-soluble materials giving o/w products. Most non-ionic surfactants are based on: a fatty acid or alcohol (usually with 12-18 carbon atoms), the hydrocarbon chain of which provides the hydrophobic moiety; an alcohol (-OH) and/or ethylene oxide grouping (- OCH 2 CH 2 -), which provide the hydrophilic par t of the molecule.  If the hydrophobic part of the molecule predominates, then the surfactant will be oil-soluble. It will not concentrate at the oil/water interface but rather tend to migrate into the oil phase. E.g span Similarly, a water-soluble surfactant will migrate into the aqueous phase and away from the oil/water interface. E.g tween The best type of non-ionic surfactant to use is one with an equal balance of hydrophobic and hydrophilic groupings. An alternative would be to use two emulgents, one hydrophilic and one hydrophobic. The cohesion between their hydrocarbon chains will then hold both types at the oil/water interface. Advantages: 1- They are not susceptible to pH change and presence of electrolytes. 2- They also show low irritancy as compared to other surfactants. 3- They also have a greater degree of compatibility with other materials than do anionic or cationic emulgents. Disadvantage: More expensive. Most commonly used nonionic surfactants are: - Glyceryl esters, - Polyoxyethylene glycol esters and ethers - Sorbitan fatty acid esters (spans) - Polyoxyethylene derivatives of sorbitan fatty acid esters (Tweens or polysorbates) - Polyoxyethylene/polyoxypropylene block polymers (Poloxamers) 5- Finely divided solid particles: They are adsorbed at the interface between two immiscible liquid phases to form particulate f ilm e.g. Mg(OH)2 and Al(OH)3 and bentonite. Finely divided solid particles are adsorbed at the surface of emulsion droplet to stabilize them. Those particles are wetted by both oil and water (but not dissolved) and the concentration of these particles form a particulate f il m that prevent the coalescence. Particles that are wetted preferentially by water from o/w emulsion , whereas those wetted more by oil form w/o emulsion Note that they are very rare to use and can affect rheology of the final product B en to n i te H ecto r i te F i n el y d i v i d ed so l i d s K ao l i n M ag n esi u m al u m i n u m si l i cate M o n tm o r i l l o n i te A l u m i nu m h y drox i de M ag esi u m h y d r o x i d e S i l i ca  Hydrophilic-Lipophilic Balance (HLB) System A convenient way to choosing emulsifiers involves the use of a numerical scale for characterization. One such approach assigns to an emulsifier a hydrophile-lipophile balance value (HLB), which is characteristic of its relative polarity. This approach is empirical and essentially no different from choosing a series of any type of emulsif ie rs. The advantage of HLB system is that to a f irst approximation one can compare any chemical type when both polar and nonpolar groups are different. With regard to the specific choice of an emulsifier, it has been suggested that surfactants having an HLB value of 3 to 6 should be used for obtaining w/o emulsions, whereas values of 8 to 18 are suitable for forming o/w emulsions.  Hydrophilic-Lipophilic Balance (HLB) System Surfactants are characterized according to the "balance" between the hydrophilic ("water-loving") and lipophilic ("oil-loving") portions of their molecules. The hydrophilic-lipophilic balance (HLB) number indicates the polarity of the molecules in an arbitrary range of 1-40, with the most commonly used emulsif iers having a value between 1 and 20. The HLB number increases with increasing hydrophilicity. Hydrophilic-Lipophilic Balance (HLB) System According to the HLB number, surfactants may be utilized for different purposes: Function HLB Range Antifoaming agent 1 to 3 Emulsifier, water-in-oil 3 to 6 Wetting agent 7 to 9 Emulsifier, oil-in-water 8 to 18 Detergent 13 to 15 Solubilizer 15 to 20  Hydrophilic-Lipophilic Balance (HLB) System The desired HLB numbers can also be achieved by mixing lipophilic and hydrophilic surfactants. The overall HLB value of the mixture is calculated as the sum of the fraction * individual HLB. Example: A mixture of 30% Span 80 (HLB=4.3) and 70% Tween 80 (HLB=15) has an overall HLB value of: HLB=(0.3 * 4.3) + (0.7 * 15)=11.8.  Identification of Emulsion Type Using of naked eye, it is very dif ficult to differentiate between o/w or w/o emulsions. Thus, the four following methods have been used to identify the type if emulsions. 1)Dilution Test (Miscibility Tests): An emulsion will mix with a liquid that is miscible with the continuous phase. Therefore an o/w emulsion is miscible with water, a w/o emulsion with an oil. Based on the solubility of external phase of emulsion. o/w emulsion can be diluted with water while w/o emulsion can be diluted with oil. 2- Conductivity Measurement: Systems with an aqueous continuous phase will conduct electricity, whilst systems with an oily continuous phase will not. Water is good conductor of electricity whereas oil is non-conductor. Therefore, continuous phase of water runs electricity more than continuous phase of oil. 3)-Dye-Solubility Test: -Water-soluble dye will dissolve in the aqueous phase. -Oil-soluble dye will dissolve in the oil phase. What is look like under the microscope after mixing with suitable dye When an emulsion is mixed with a water soluble dye such as amaranth and observed under the microscope, if the continuous phase appears red, then it means that the emulsion is o/w type as water is the external phase and if the scattered globules appear red and continuous phase colorless , then it is w/o type. 4-Fluorescence test: Oils give f lu orescence under UV light, while water doesn’t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces. Methods of Preparation Thank You