Tuesday, April 25, 2017

EMULSIONS

DISPERSE SYSTEM
In which one substance is distributed in particulate form throughout another
Two types
Emulsion
Is a biphasic liquid preparation containing two immiscible liquids one of which is dispersed as minute globules into other and stabilized by a third substance called emulsifying agent.
The droplet phase is called the dispersed phase or internal phase and the liquid in which droplets are dispersed is called the external (continuous phase).
Suspension
Is a two phased system in which a finely divided solid is dispersed in a continuous phase of solid, liquid, or gas.
The droplet phase is called the dispersed phase or internal phase and the liquid in which droplets are dispersed is called the external (continuous phase).
Classification of Emulsion
Based on:
Oil in Water (O/W): Oil droplets dispersed in water
Water in Oil (W/O): Water droplets dispersed in oil
(Diameter greater than
 0.1 μm)

Dispersed phase                            
Simple emulsions
(Macro emulsions)




Multiple emulsions
Oil-in-water-in-oil (O/W/O)
Water-in-oil-in-water (W/O/W)


Nano emulsions
Thermodynamically stable optically transparent, mixtures of a biphasic oil –water system stabilized with surfactants
0.01 – 0.2 mm Micro emulsions (Thermody-namically stable)



Micro emulsions






TYPES OFEMULSIONS:
1. Macroemulsions (Simple Emulsions):
I. Oil in water (o/w): Oil droplets are dispersed in a continuous aqueous phase. This emulsion is generally formed if the aqueous phase constitutes more than 45 % of the total weight and a hydrophilic emulsifier is used. These are [referred for oral administration and cosmetics. These are useful as water washable drug bases .The globule size is 0.25 to 10 microns.
ii. Water in oil (w/o):  Aqueous droplets are dispersed in continuous oily phase. . This emulsion is generally formed if the oily phase constitutes more than 45 % of the total weight and a lipophobic emulsifier is used. These are used for cosmetics. They are employed for treatment of dry skin and emollient applications.
2. Multiple emulsions:
Types of multiple emulsions:  w/o/w , o/w/o
They are developed with a view to delay the release of an active ingredient. They have three phases. They may be oil-in-water-in-oil (o/w/o) or of water-in-oil-in-water (w/o/w). An emulsifier is present to stabilize the emulsions and various ionic and nonionic 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 o/w systems In these emulsions within emulsions any drug present in innermost phase must now  cross two phase boundaries to reach the external continuous phase. Such emulsions also can invert. However, during inversion they form simple emulsions. So a w/o/w emulsion will get inverted to o/w emulsion.
Preparation of multiple emulsions:
Aqueous phase is added to oily phase, containing a lipophilic surfactant. Upon mixing a w/o emulsion is formed. This w/o emulsion is then poured into a second aqueous solution,contain za hydrophilic surfactant. Upon mixing multiple emulsion w/o/w is formed.
3. Microemulsions:
          They may be defined as dispersions of insoluble liquids in a second liquid that appears clear and homogenous to the naked eye. They are frequently called solubilised systems because on a macroscopic basis they seem to behave as true solutions.  Terms as transparent emulsions, micellar solutions, solubilised systems, and swollen micelle have all been applied to the same or similar systems.
        These emulsions appear to be transparent to the eye. They have globule radius below the range of 10-75 nm. The appearance of emulsion depends on the wavelength of visible light i.e. globules less than 120 nm do not reflect light and appear transparent to the eye. As in microemulsions the globule size is less than 120 nm, they appear to be transparent.
USES (APPLICATIONS) OF EMULSIONS:
Emulsions can be used for oral, parenteral or topical pharmaceutical dosage forms.
i. Oral Products
Emulsions are used for administering drugs orally due to following reasons:
a. More palatable: Objectionable taste or texture of medicinal agents gets masked.
b. Better absorption: Due to small globule size, the medicinal agent gets absorbed faster.
ii. Topical products:
O/W emulsions are more acceptable as water washable drug bases for cosmetic purposes.
W/O emulsions are used for treatment of dry skin. Emulsions have following advanyages when used for topical purpose:
A.    Patient acceptance: Emulsions are accepted by patients due to their elegance, easily
B.     washable character,
C.     acceptable viscosity,
D.    less greasiness.
iii. Parenteral Emulsions:
A.    i.v rout:  Lipid nutrients are emulsified and given to patients by i/v rout. Such emulsions have particle size less than 100 nm.
B.     Depot injections : W/o emulsions are used to disperse water soluble antigenic materials in mineral oil for i/m depot injection.
    iii.            Diagnostic purposes:
    iv.            Radio opaque emulsions have been used in X-ray examination.
Identification test of emulsion
Dilution test:
In this test the emulsion is diluted either with oil or water. If the emulsion is o/w type and it is diluted with water, it will remain stable as water is the dispersion medium" but if it is diluted with oil, the emulsion will break  as oil and water are not miscible with each other.
*      o/w emulsion can be diluted with water.
*        w/o emulsion can be diluted with oil.
                                                                     
Conductivity Test
The basic principle of this test is that water is a good conductor of electricity. Therefore in case of o/w emulsion, this test will be positive as water is the external phase. ‘In this test, an assembly is used in which a pair of           electrodes connected to an electric bulb is dipped into an emulsion. If the emulsion is o/w type, the electric bulb glows.’
Dye-Solubility Test
In this test an emulsion is mixed with a water soluble dye (amaranth) and observed under the microscope. If the continuous phase appears red, it means that the emulsion is o/w type as water is in the external phase and the dye will dissolve in it to give color. If the scattered globules appear red and continuous phase colorless, then it is w/o type. Similarly if an oil soluble dye (Scarlet red C or Sudan III) is added to an emulsion and the continuous phase appears red, then it is w/o emulsion.
Fluorescence Test:
Oils give fluorescence under UV light, while water doesn’t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces.  When a w/o emulsion is exposed to fluorescent light under a microscope the entire field fluorescence. If the fluorescence is spotty, then the emulsion is of o/w-type. However, all oils do not exhibit fluorescence under UV light and thus the method does not have universal application. It is necessary that the results obtained by one method should always be confirmed by means of other methods
Cobalt Chloride Test:
Filter paper impregnated with CoCl2 and dried appear to be blue but when dipped in o/w emulsion changes to pink. This test may fail if emulsion unstable or breaks in presence of electrolyte.
FORMULATION OF EMULSIONS
1.      Emulsifying agents (emulsifiers)
2.      Antioxidants (Stabilizers)
3.      Antimicrobial preservatives
4.      Colours and flavourings
Emulsifying agents (emulsifiers):
An emulsifying agent is any material that enhances the stability of an emulsion (i.e. Prevention of coalescence and reducing creaming).The ideal emulsifying agent is colourless, odourless, tasteless, non-toxic, non-irritant and able to produce stable emulsions at low concentrations.
Classification of Hydrocolloid emulsifying agents
        i.            Hydrocolloids.
      ii.            Surface active agents (SAA) (surfactants).
    iii.            Finely divided solids.
    iv.            Auxiliary emulsifiers.

 Natural emulsifying agents. :
Natural    (Multimolecular films)
Ø  From plant origin Polysaccharides ( Acacia, tragacanth, agar, pectin, lecithin) o/w emulsions.
Ø  From animal origin
Ø  Proteins ( Gelatin) o/w emulsions.
Ø  Lecithin, o/w i/v emulsion
Ø  Cholesterol. w/o
Ø  Wool fat, w/o

i. Natural emulsifying agents from vegetable sources
These consist of agents which are carbohydrates and include gums and mucilaginous substances. Since these substances are of variable chemical composition, these exhibit considerable variation in emulsifying properties. They are anionic in nature and produce o/w emulsions. They act as primary emulsifying agents as well as secondary emulsifying agents (emulsion stabilizers). Since carbohydrates acts a good medium for the growth of microorganism, therefore emulsions prepared using these emulsifying agents have to be suitable preserved in order to prevent microbial contamination. E.g. tragacanth, acacia, agar, chondrus (Irish moss), pectin and starch.
Acacia:It is a carbohydrate gum which is soluble over a wide pH range. Tragacanth, pectin and starch are used as auxiliary emulsifying agents.
ii. Natural emulsifying agents from animal source
The examples include gelatin, egg yolk and wool fat (anhydrous lanolin).
Gelatin:
It is a protein .It has two isoelectric points, depending on the method of preparation. Type a gelatin derived from acid treated precursor, has an isoelectric point between pH 7 and 9. Type B gelatin obtained from an alkaline precursor has an isoelectric point around pH 5. . Type A gelatin acts best as an emulsifier around pH 3 where it is -vely chaged: On the other hand type B gelatin suitable as emulsifier at pH 8 where it is –vely charged.Type A gelatin (Cationic) is generally used for preparing o/w emulsion while type B gelatin is used for o/w emulsions of pH 8 and above.
Lecithin:
It is an emulsifier obtained from both plant (soyabean) and animal (e.g. egg yolk) sources and is composed of phosphatides. Although the   primary component of most lecithins is phosphatidyl choline. But it also contains phosphatidyl srine, phosphatidyl inositol, phosphatdylethanloamine and phosphatidic acid.. It imparts a net –ve charge to dispersed particles. They show surface activity and are used for formulating o/w emulsions. Lecithins are good emulsifying agents for naturally occurring oils such as soy, corn, or safflower. Purified lecithin from soy or egg yolk is used for i/v emulsions.
cholesterol:
It is a major constituent of wool alcohols, obtained by the saponification and fractionation of wool fat. It forms w/o emulsion. It is because of cholesterol that wool fat absorbs water and form a w/o emulsion It is also present in egg yolk.
Wool fat
It is mainly used in w/o emulsions meant for external use. They absorb large quantities of water and form stable w/o emulsions with other oils and fats.

Classification of Surfactant emulsifying agents
Ø  Synthetic  (Surfactants)  ( Monomolecular films)
·         Cationic
·         Quaternary ammonium compounds
Ø  Nonionic
·         Glyceryl esters
·         Sorbitan fatty acid esters
·         Polyoxyethylene polyoxypopylene esters (Macrogels)
·         Polyoxyethylene derivatives of sorbitan fatty acid esters (polysorbate)
Synthetic emulsifying agents (Surfactants):
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 film. This film acts as a mechanical barrier and prevents coalescence of the globules of the dispersed phase. They are classified according to the ionic charge possessed by the molecules of the surfactant e.g., anionic, cationic, non-ionic and ampholytic.They may be subdivided into anionic, cationic and nonionic surfactants.
i. Anionic Surfactants:The long anion chain on dissociation imparts surface activity, while the cation is inactive. These agents are primarily used for external 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, sulphated alcohols and alkyl sulphonates.
a. Monovalent soaps: E.g. potassium, sodium, ammonium salts of lauric and oleic acid. They are soluble in water and are good o/w emulsifying agents.
Disadvantages:
They have disagreeable taste and are irritating to the GIT.. So they are useful only for external use emulsions.
They have a high pH . They get ppted below pH 10 because the unionized fatty acid is formed which has a low aqueous solubility. So emulsions formed with alkali soaps are not stable at pH less than 10.
b. Polyvalent soaps: The calcium, magnesium and aluminum salts of fatty acids (metallic soaps) are water insoluble and give w/o emulsion.
c. Organic soaps: Triethanol amine soaps of fatty acids give o/w emulsion. They are used for external use emulsions. They are less alkaline as compare to monovalent soaps. They can act till pH 8.00
d. Sulfated alcohols: They are neutralized estrs of sulfuric acid and fatty alcohols. They can be used as auxiliary emulsifying agents. E.g Sodium lauryl sulphate
e. Sulfonates : In these compounds the sulfur atom is connected directly to the carbon atom, giving the general formula
CH3 (CH2) n CH2SO3 – Na+
e.g. sodium lauryl sulphate , dioctyl  sulphosuccinate.
ii. Cationic Surfactants: The positive charge cations produced on dissociation are responsible for emulsifying properties. They are mainly used in external preparations such as lotions and creams. Quaternary ammonium compounds such as cetrimide, 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.
Quaternary ammonium compounds (cetyl trimethyl ammonium bromide; cetrimide)
CH3 (CH2)14 N+ (CH3)34Br
They have marked bactericidal activity. So they are useful for anti-infective products such as skin lotions and creams. The pH of an emulsion prepared with cationic emulsifier is in pH 4 -6 range. This is the range of normal pH of skin. So they are suitable for skin. They are comparatively weak emulsifying agents, so they are used along with auxiliary emulsifying agents such as cetostearyl alcohol. They are incompatible with anionic surfactants.
Nonionics :
They are the class of surfactants widely used as emulsifying agents. They are extensively used to produce both oil in water and water in oil emulsions for internal as well as external use.
Advantages: They are not susceptible to pH change and presence of electrolytes.
They also show low irritancy as compared to other surfactants.
Most commonly used nonionics 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)
  • Glyceryl esters :  e.g. glyceryl mono stearate. It is too lipophilic to be used as a primary emulsifying agent. It is used as auxiliary emulsifying agent.
Sorbitan fatty acid esters : e.g. sorbitan mono oleate. They are oil soluble nonionic surfactants.and give w/o emulsions.
  • Polyoxyethylene derivatives of sorbitans fatty acids : They are hydrophilic and give o/w emulsion.    
  • Polyoxyethylene/polyoxypropylene block poymers , also known as poloxamers consist of combined chains of oxyethylene with oxypropylene where the oxyethylene portions imparts hydrophilicity and oxypropylene portion imparts lipophilicity. The molecules are synthesized as long segments of hydrophilic portions combined with long segments of the hydrophilic portions, with each portion referred to as block. They are used in the formulation of i/v emulsions and can impart structures to vehicles and interfacial films.
  • Ampholytic surfactants: These are the substances whose ionic charge depends on the pH of the system. Below a certain pH, these are cationic while above a defined pH, these are cationic. At intermediate pH these behave as zwitterions. e.g. lecithin.
  • Includes mainly cellulose derivatives like sodium carboxy methyl cellulose, hydroxyl propyl cellulose and methyl cellulose. They are used for formulating o/w type of emulsions. They primarily act by increasing the viscosity of the system. e.g., methyl cellulose, hydroxypropyl cellulose and sodium carboxy methyl cellulose
Finely dispersed solids:
Finely divided solid particles that are wetted to some degree by both oil and water act as emulsifying agents. This results from their being concentrated at interface, where they produce a particulate film around the dispersed droplets to prevent coalescence.They form particulate films around the dispersed droplets, producing emulsions which are coarse grained but stable. Colloidal clays like bentonite, veegum are the examples of finely divided solids used as emulsifying agents.
Bentonite : It is a gray, odorless and tasteless powder which swells in the presence of water to form a suspension with a pH of about 9. Depend on the order of mixing, both o/w or w/o emulsion can be formed with bentonite. For o/w emulsion, bentonite is first dispersed in water and allowed to hydrate to form magma. Then oil phase is gradually added with constant agitation. To prepare w/o emulsion, bentonite is first dispersed in oil and then water is added gradually.
Veegum : Used as stabilizer in concentration of 1% for  cosmetic lotions and creams.  Prepared with anionic or non-ionic emulsifying agents.
Auxiliary emulsifying agents
Auxiliary (Secondary) emulsifying agents include those compounds that are normally incapable themselves of forming stable emulsion. Their main value lies in their ability to function as thickening agents and thereby help stabilize the emulsion.These are those compounds which normally cannot form an emulsion on their own but can function as thickening agents and stabilize the emulsion. Sometimes they increase the viscosity of the external phase and help restricting the collisions of droplets.. Some of them prevent coalescence by reducing van de waals forces between particles or by providing a physical barrier between droplets. Proteins, semisynthetic polysaccharides (methyl cellulose, carboxy mthyl cellulose), clays can be used as auxiliary agents.
Antimicrobial agents
Emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols and phosphatides.All of which readily support the growth of a varity of microorganisms. Even in the absence of any of the above mentioned ingredients, the mere presence of a mixture of lipid and water in intimate contact frequently allows microorganisms growth. So preservative is a must for emulsions. Microbial contamination may occur due to:Contamination during development or production of emulsion or during its use.Usage of impure raw materials.Poor sanitation conditions. Invasion by an opportunistic microorganisms.Contamination by the consumer during use of the product. Precautions to prevent microbial growth ;Use of uncontaminated raw materialsCareful cleaning of equipment with live straem .
Preservation :
Once a microbiologically uncontaminated product has been formed, a relatively mild antimicrobial agent is sufficient to protect the product against microbial contamination. The preservative system must be effective against invasion by a variety of pathogenic organisms and protect the product during use by consumer.The preservative must be :Less toxic, Stable to heat and storage, Chemically compatible, Reasonable cost, Acceptable taste, odor and color.Effective against fungus, yeast, bacteria.
Available in oil and aqueous phase at effective level concentration.
          Acids and acid derivatives - Benzoic acid - Antifungal agent
           Aldehydes –  Formaldehyde - Broad spectrum
          Phenolics - Phenol - Broad spectrum
                       Cresol
                       Propyl p-hydroxy benzoate
          Quaternaries -Chlorhexidine and salts  - Broad spectrum
                        Benzalkonium chloride
                        Cetyl trimethyl ammonium bromide
          Mercurials -Phenyl mercuric acetate - Broad spectrum
Colours and flavourings
Colour is rarely needed in an emulsion, as most have an elegant white colour and thick texture. Emulsions for oral use will usually contain some flavouring agent.
The HLB ( Hydrophilic lipophilic balance system):
An HLB number (1-20) represents the relative proportions of the lipophilic and hydrophilic parts of the molecule. High numbers (8-18) indicate a hydrophilic molecule, and produce an o/w emulsion.Low numbers (3-6) indicate a lipophilic molecule and produce a w/o emulsion. Oils and waxy materials have a 'required HLB number' which helps in the selection of appropriate emulsifying agents when formulating emulsions. Liquid paraffin, for example, has a required HLB value of 4 to obtain a w/o emulsion and 12 for an o/w emulsion.
HLB ca. 3.5 to 8: Water-in-Oil Emulsifiers
HLB ca. 1 to 3.5: Antifoams
HLB ca. 7 to 9: Wetting and spreading agents
HLB ca. 8 to 16: Oil-in-Water Emulsifiers
HLB ca. 13 to 16: Detergents
HLB ca. 15 to 40: Solubilizers

Methods of Preparation Of Emulsions
Commercially, emulsions are prepared in large volume mixing tanks and refined and stabilized by passage through a colloid mill or homogenizer. Extemporaneous production is more concerned with small scale methods.
1) Dry Gum Methods
2) Wet Gum Methods
3) Bottle Method
4) Beaker Method.
5) In situ Soap Method
DRY GUM Method (Continental method)
Dry gum method is used to prepare the initial or primary emulsion from oil, water, and a hydrocolloid or "gum" type emulsifier.  (4 parts oil, 2 parts water, and 1 part Emulsifier).
Ratio of oil: gum: water in primary emulsion
Fixed oil      = 4:1:2
Mineral oil   = 3:1:2
Volatile oil   = 2:1;2
Procedure: Take mortar, 1 part gum is levigated with the 4 parts oil until the powder is thoroughly wetted; then the 2 parts water are added all at once, and the mixture is vigorously triturated until the primary emulsion formed is creamy white and produces a "crackling" sound as it is triturated. Active ingredients, preservatives, color, flavors are added as a solution to the primary emulsion. When all agents have been incorporated, the emulsion should be transferred to a calibrated vessel, brought to final volume with water.Oil soluble substances in small amounts may be incorporated directly into the primary emulsion.  Any substance which might reduce the physical stability of the emulsion, such as alcohol ( which may  precipitate the gum) should  be added as near to the end of the process as possible to avoid breaking the emulsion. When all agents have been incorporated , the emulsion should be transferred to a calibrated vessel, brought to final volume with water, then homogenized or blended to ensure uniform distribution of ingredients.
Wet Gum Method (English method)
(Oil 4 parts + Water 2 parts + Emulsifier 1 parts)
Procedure: In this method, the proportions of oil, water, and emulsifier are the same (4:2:1), but the order and techniques of mixing are different. The 1 part gum is triturated with 2 parts water to form a mucilage; then the 4 parts oil is added slowly, in portions, while triturating. After all the oil is added, the mixture is triturated for several minutes to form the primary emulsion. Then other ingredients may be added as in the continental method. Generally speaking, the English method is more difficult to perform successfully, especially with more viscous oils, but may result in a more stable emulsion.
Bottle Method
This method may be used to prepare emulsions of volatile oils, Oleaginous substances of very low viscosities.This method is a variation of the dry gum method. One part powdered acacia (or other gum) is placed in a dry bottle and four parts oil are added. The bottle is capped and thoroughly shaken. To this, the required volume of water is added all at once, and the mixture is shaken thoroughly until the primary emulsion forms.
Beaker Method
The most appropriate method. Dividing components into water soluble and oil soluble components. All oil soluble components are dissolved in the oily phase in one beaker and all water soluble components are dissolved in the water in a separate beaker. Oleaginous components are melted and both phases are heated to approximately 70°Cover a water bath. The internal phase is then added to the external phase with stirring until the product reaches room temperature.
In situ Soap Method
Two types of Soaps developed by this Methods:
1) Calcium Soaps
2) Soft Soaps
Calcium Soaps: W/O type Emulsions. E.g. Oleic acid + Lime water. Prepared by simple mixing of equal volumes of Oil and Lime water.Emulsifying agent used is Calcium salt of free fatty acids. E.g. Olive Oil + Oleic acid (FAA) = calcium Oleate.Advantage: O/W is external Phase used frequently  on dry skin and sun burned skin.
Large Scale Methods
Physical parameters affecting the droplet size distribution viscosity, and stability of emulsion: Location of the emulsifier, method of incorporation of the phases, the rates of addition , the temperature of each phase and the rate of cooling after mixing of the phases considerably
Energy may be supplied in the form of:
¢  Heat
¢  Homogenization
¢  Agitation
Mechanical equipment for emulsification (Agitation)
Mechanical Stirrers
An emulsion may be stirred by means of various impellers mounted on shafts, which are placed directly into the system to be emulsified. This is used for mixing, suspending, milling, dispersing, disintegrating solids etc. & reduces batch time. It consists of stator and rotor assembly. The rotor rotates inside the stator assembly which is fixed with three tie rods to the motor.
Propeller Mixers
Simple top entering propeller mixers are adequate for routine development work in the laboratory and production.The degree of agitation is controlled by propeller rotation but the pattern of liquid flow and resultant efficiency of mixing are  controlled by the type of impeller, its position in the container, the presence of baffles, and the general shape of the container. These stirrers can not be used when  :vigorous agitation is needed,
Extremely small droplets are needed.
Foaming at high shear rates must be avoided.These mixers may have  paddle blades, counter rotating blades or planetary  blades .
¢  Homogenizers
In homogenizers the dispersion of two liquids is achieved by forcing their mixture through a small inlet orifice at big pressures. Homogenizers can be made with more than one emulsifying stage, and it is possible to recycle the emulsion through the homogenizer more than one time. Homogenizers raise the temp. Of the emulsion, hence cooling may be required. It can be used when a reasonably mono disperse emulsion of small droplet size (1 nm) is required.
Colloid Mills
They operate on principle of high shear which is normally generated between rotor and stator of the mill.Colloid mill consists of a fixed stator plate and a high speed rotating rotator plea.
Material drawn or pumped through an adjustable gap set between the rotor and stator is homogenized by the physical action and the centrifugal force is created by high rotation of the rotor which operates within 0.005 to0.010 inch of the stator
Ultrasonifiers
Ultrasonic energy s used to produce pharmaceutical emulsions. These transduced piezoelectric devices have limited output and are expensive. They are useful for laboratory preparation of emulsions of moderate viscosity and extremely low particle size. Commercial equipment is based n principle of Pohlmn liquid whistle. The dispersion is forced through an orifice at modest pressure and is allowed to impinge on a blade. The pressure range is from 150-350 psi . This pressure causes blade to vibrate rapidly to produce an ultrasonic note. When the system reaches a steady state, a cavitational field is generated at the leading edge of the blade and the pressure fluctuations of approx. 60 tones psi can be achieved in commercial equipment.
Emulsions for oral use
Quantities for primary emulsions
Example: Calculate the quantities for a primary emulsion for the following:

    Cod liver oil                30 ml
    Water                          to 100 ml

Answer: Primary emulsion quantities:
     Cod liver oil is a fixed oil, therefore the primary emulsion proportions are 4 : 2 : 1 .Hence:
Cod liver oil                                         30 ml                 4
Water                                                  15 ml                  2
Powdered acacia gum                      7.5g                    1
If the proportion of oil is too small, modifications must be made. Acacia emulsions containing less than 20% oil tend to cream readily. A bland, inert oil, such as arachis, sesame, cottonseed or maize oil, should be added to increase the amount of oil and so prevent this from happening. Care should be taken in selection of the bulking oil because of the increasing incidence of nut allergy. It is often, therefore, advisable to avoid oils such as arachis, especially for children.
Example: Rx Calciferol solution, 0.15 ml per 5 ml dose.
Answer: The percentage of oil in each dose is 3%. The oil content must be made up to at least 20% to produce a stable emulsion.  Since 20% of 5 ml = 1 ml the volume of bland oil required is 1-0.15 = 0.85 ml
Formula for primary emulsion (for 50 mL)
Calciferol solution              1.5 ml                             4
Cottonseed oil                     8.5 ml                  
Water                                    5 ml                                 2
Acacia                                    2.5g                                 1
The primary emulsion may not form and a thin oily liquid is formed instead. Possible causes are:
Phase inversion has occurred, incorrect quantities of oil or water were used, and Cross-contamination of water and oil, a wet mortar was used, The mortar was too small and curved or the pestle was too round giving insufficient shear, Excessive mixing of oil and gum before adding water (dry gum method), Diluting the primary emulsion too soon or too rapid dilution of primary emulsion, Poor-quality acacia
Prepare 200ml cod liver oil emulsion to the following formula:
Cod liver oil                       60 ml
Chloroform                        0.4ml
Cinnamon water              to 200ml
100ml Liquid Paraffin Oral Emulsion BP 1968.
Liquid paraffin                    50ml
Vanillin                               50mg
Chloroform                         0.25ml
Benzoic acid solution          2ml
Methylcellulose 20               2g
Saccharin sodium                5mg
Water                                to 100ml
Emulsions for external use
Liquid or semi-liquid emulsions may be used as applications, liniments and lotions. The extemporaneous preparation of emulsions for external use does not require the preparation of a primary emulsion. Soaps are commonly used as the emulsifying agent and some are prepared 'in situ' by mixing the oily phase containing a fatty acid and the aqueous phase containing the alkali. Alternatively the emulsifying agent can be dissolved in the oily or aqueous phase and the disperse phase added to the continuous phase, either gradually or in one portion.Creams are semisolid emulsions which may be o/w (e.g. aqueous cream) or w/o (e.g. oily cream). Applications: solutions or emulsions that frequently contain parasiticides. Liniments: alcoholic or oily solutions or emulsions designed to be rubbed into the skin. The medicament is usually a rubefacient.Lotions : aqueous solutions, suspensions or emulsions that cool inflamed skin and deposit a protective layer of solid.
Creams are semisolid emulsions which may be o/w (e.g. aqueous cream) or w/o (e.g. oily cream).
Rx 100ml Oily Calamine Lotion 1980
Calamine                                      5g
Wool fat                                       1g
Oleic acid                                     0.5ml
Arachis oil                                    50ml
Calcium hydroxide solution    to 100ml

Shelf life, storage, containers
Emulsions should be stored at room temperature and will either be recently or freshly prepared. Some official preparations will have specific expiry dates. They should not be frozen.A plain amber medicine bottle is used for internal use with an airtight child-resistant closures.Containers with a wide mouth are useful for very viscous preparations.
Instability of emulsions    
1)      Flocculation and creaming
2)      Coalescence and breaking
3)      Phase inversion.
4)      Miscellaneous physical and chemical changes

Flocculation
Neighboring globules come closer to each other and form colonies in the continuous phase. This aggregation of globules is not clearly visible. This is the initial stage that leads to instability. Flocculation of the dispersed phase may take place before, during or after creaming.The extent of flocculation of globules depends on 
                                           (a) globule size distribution.
                                           (b) charge on the globule surface.
                                           (c) viscosity of the external medium.
a.       Globule size distribution
Uniform sized globules prevent flocculation. This can be achieved by proper size reduction process.
b.      Charge on the globule surface
A charge on the globules exert repulsive forces with the neighboring globules. This can be achieved by using ionic emulsifying agent, electrolytes etc.
c.       Viscosity of the external medium.
If the viscosity of the external medium is increased, the globules become relatively immobile and flocculation can be prevented. This can be obtained by adding viscosity improving agents (bodying agents or thickening agents) such as hydrocolloids or waxes. Flocs slowly move either upward or downward leading to creaming. Flocculation is due to the interaction of attractive and repulsive forces, whereas creaming is due to density differences in the two phases.
Creaming
Creaming is the concentration of globules at the top or bottom of the emulsion. Droplets larger than 1 mm may settle preferentially to the top or the bottom under gravitational forces.Creaming may also be observed on account of the difference of individual globules (movement rather than flocs). It can be observed by a difference in color shade of the layers.It is a reversible process, i.e., cream can be redispersed easily by agitation, this is possible because the oil globules are still surrounded by the protective sheath of the emulsifier. Creaming results in a lack of uniformity of drug distribution. This leads to variable dosage. Therefore, the emulsion should be shaken thoroughly before use. Creaming is of two types, upward creaming and downward creaming
Upward creaming, is due to the dispersed phase is less dense than the continuous phase. This is normally observed in o/w emulsions. The velocity of sedimentation becomes negative.Downward creaming occurs if the dispersed phase is heavier than the continuous phase. Due to gravitational pull, the globules settle down. This is normally observed in w/o emulsions.Since creaming involves the movement of globules in an emulsion, Stokes’ law can be applied.
            ν =      d2 (ρsρ0)g
18 η0
ν = terminal velocity in cm/sec,
d is the diameter of the particle in cm,
ρs and ρ0 are the densities of the dispersed phase and dispersion medium respectively,
g is the acceleration due to gravity and
η0 is the viscosity of the dispersion medium in poise.
Creaming is influenced by,
      Globule size
      Viscosity of the dispersion medium
      Difference in the densities of dispersed phase and dispersion medium.
Creaming can be reduced or prevented by:
Reducing the particle size by homogenization. Doubling the diameter of oil globules increases the creaming rate by a factor of four.Increasing the viscosity of the external phase by adding the thickening agents such as methyl cellulose tragacanth or sodium alginate.Reducing the difference in the densities between the dispersed phase and dispersion medium. Adjusting the continuous phase and dispersed phase densities to the same value should eliminate the tendency to cream. To make densities equal, oil soluble substances such as bromoform, β-bromonaphthalene are added to the oil phase (rarely used technique).
Coalescence
If the sizes of globules are not uniform, globules of smaller size occupy the spaces between the larger globules. A few globules tend to fuse with each other and form bigger globules.This type of closed packing induces greater cohesion which leads to coalescence. In this process, the emulsifier film around the globules is destroyed to a certain extent. This step can be recognized by increased globule size and reduced number of globules.
Coalescence is observed due to:
Ø  Insufficient amount of the emulsifying agent.
Ø  Altered partitioning of the emulsifying agent.
Ø  Incompatibilities between emulsifying agents.
Phase volume ratio of an emulsion has a secondary influence on the stability of the product and represents the relative volume of water to oil in emulsion.At higher ratio (>74% of oil to water), globules are closely packed, wherein small globules occupy the void spaces between bigger globules.Thus globules get compressed and become irregular in shape, which leads to fusion of adjacent globules.Ostwald and others have shown that if one attempts to incorporate more than about 74% of oil in an o/w emulsion, the oil globules often coalesce and the emulsion breaks. This value known as the critical point, is defined as the concentration of the dispersed phase above which the emulsifying agent cannot produce a stable emulsion of the desired type.
Breaking (cracking)
Separation of the internal phase from the external phase is called breaking of the emulsion. This is indicated by complete separation of oil and aqueous phases, is an irreversible process, i.e., simple mixing fails. It is to resuspend the globules into an uniform emulsion. In breaking, the protective sheath around the globules is completely destroyed and oil tends to coalesce.

Phase inversion
This involves the change of emulsion type from o/w to w/o or vice versa.
When we intend to prepare one type of emulsion say o/w, and if the final emulsion turns out to be w/o, it can be termed as a sign of instability. It may due to
       By addition of an electrolyte
       By changing Phase-Volume ratio
       By temperature change
       By changing emulsifying agent

       It can be minimized by keeping concentration of disperse phase between 30-60%

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