MANUF LAB - Emulsions

Emulsions

A heterogenous system of 2 immiscible liquids which are mixed using mechanical shear and surfactant

Poorly soluble, or have low bioavailability or dissolution rates

Emulsions may provde an efficient means of administering drugs that are ________, or have _________ or __________, increasing both dissolution rates and absorption to increase bioavailability and improve bioavailability.

Surface area

By increasing ____________ provided by an emulsion, dissolution rates and absorption rates of drugs are increased, improving their bioavailability.

Topical drug delivery

Emulsions are widely utilized as bases for _________ drug delivery formulations, such as creams, lotions, and ointments.

Lipophilic as well as hydrophilic

Their incorporation allows ________ as well as _________ drugs to be mixed together for maximum skin penetration and permeation of active ingredients.

Intravenous or intramuscular

Emulsions serve as carriers for ______ or _________ administration of drugs, solubilizing lipophilic ones while protecting from degradation and decreasing injection site irritation.

Propofol

Example of parenteral emulsion include _________, as a widely used anesthetic and lipid-based solutions used for Total Parenteral Nutrition Delivery

Ocular

Emulsions can be used to formulate eye drops and other ______ drug delivery systems, increasing drug retention time in the eye and permeating through corneal barriers more easily while providing sustained release of active ingredients and thus increasing therapeutic efficacy

Oil in water; Water in oil; Multiple emulsions (e.g. w/o/w emulsions)

Types of emulsions based on dispersed phase (3)

Oil in water emulsions

[Types of emulsions] A type wherein droplets are dispersed in water

Fats and oils; fat soluble drugs and vitamins, unpleasant tasting drugs

[Types of emulsions] Oil in water emulsions are used for the administration and as vehicles of ________ (3)

Oral administration, Intravenous (IV) injection

[Types of emulsions] O/W emulsions are ideal for these routes of administration (2)

Water, soya oil, egg lecithin

[Types of emulsions] Propofol emulsion for IV use is an O/W emulsion containing lipid-soluble Propofol emulsified in a mixture of _____________

Water in oil Emulsions

[Types of emulsions] A type wherein water droplets are dispersed in oil

Dispersion of antigenic materials, water-soluble drugs in mineral oil

[Types of emulsions] W/O emulsions are used as a vehicle for the dispersion of ________, and vehicle for __________

Intramuscular (IM) injection, Topical Application

[Types of emulsions] W/O Emulsions are preferred for these routes of administration (2)

0.1 to 100 microns

With most methods of preparations, emulsions droplets will have a droplet size diameter from ___ to ____ microns

Colloidal behavior

if the diameter is less than 0.1 micron, the emulsion can exhibit __________ behavior and a higher degree of stability

Dermatological, medicinal, and cosmetic uses

Emulsion bases containing oils and lipids are used for __________/ _________, and _________ uses

O/W Emulsions

________ emulsions command more attention today because of its greater applications and uses

Macroemulsions

[Emulsions based on Size of Liquid Droplets] 0.2 - 50 mm

Microemulsions

[Emulsions based on Size of Liquid Droplets] 0.01 - 0.2 mm

Nanoemulsions

[Emulsions based on Size of Liquid Droplets] 50 - 1000 nm

Knowledge of the various processes involved in emulsification

General considerations in Emulsification: First consideration

Surface tension theory, oriented wedge theory, interfacial film/plastic film theory, viscosity theory

Theories of Emulsification Process (4)

Surface Tension Theory of Emulsification

This theory states that surface-active agents reduce the interfacial tension between two immiscible liquids, reducing the repellent force between both the liquids and decreasing the attraction of each liquid for its own molecules

Surface active agents (surfactants)

In the surface tension theory of emulsification, the ______ are used

Oriented Wedge Theory

According to this theory, monovalent soap like sodium stearate give o/w type of emulsion. This was explained by successful accommodation of the soap molecules to give the type of emulsion.

Interfacial Film Theory

In accordance with this theory, the added emulsifying agent reduces the interfacial tension between the oil and water phases and thus a stable emulsion is formed. This theory could not explain the formation of type of emulsion.

Viscosity theory

Emulgents like acacia and tragacanth, which are hydrocolloids, as well as PEG (polyethylene glycol), glycerine, and other polymers like CMC (carboxymethyl cellulose), all increase the viscosity of the medium, which helps create and maintain the suspension of globules of dispersed phase.

Influence in viscosity

General considerations in Emulsification: Second consideration

Emulsification process; Types of emulsion formed

The viscosity of each phase of an emulsion influences the following: (2)

Viscosity

The __________ of the external phase influences the rate of droplet movement during the initial period of emulsion formation.

Lesser

The greater the viscosity, the ____________ the rate of droplet movement.

Brookefield viscometer

The viscosity of an emulsion and suspension can be determined by a ____________

Emulsion stability

General considerations in Emulsification: Third consideration

Coalescence, flocculation, creaming, sedimentation

The major concern of the formulator must be the maintenance of a stable product without appropriate phase separation. This is influenced by the following factors: (4)

Flocculation

It is caused by the aggregation of particles of the dispersed phase

Oil in water emulsions

Flocculation is generally found in what type of emulsions

Aggregation

Other term for flocculation

Flocculation

The dispersed droplets com together but do not fuse.

Creaming

It is caused by the influence of buoyancy or centripetal force

Dairy products

Creaming can be found in ________ products when they are left for a long time.

Coalescence

The complete fusion of droplets leads to a decrease in the number of droplet and ultimate separation of the 2 immiscible liquids.

Coalescence

It is caused by increasing the average particle size of the discontinuous phase

Fog

Coalescence can be seen in the ____________

Breaking

It is the complete separation of oil and water

Inversion

it is when the emulsion changes from an O/W to a W/O emulsion or vice versa

Addition of electrolyte; Phase volume ratio

Inversion can be brought about by the addition of an _________________ or by changing the ________________________

Basis of Experience; Personal Tastes of the Formulator; Considerable Trial and Error Experimentation

Selection of Materials and the Quantities Required to Formulate A Desired Emulsion (3)

Ultimate use of the product; Potential toxicity of the oil; Consistency desired; Possible chemical incompatibilities with other ingredients

The materials making up the oil phase of the emulsion and its relative amounts are determined by the following conditions

Phase volume ratio

It refers to the proportion of the internal and external volumes of emulsions

40-60% internal phase volume

For fluid emulsions, it is suggested that a _______ internal phase volume produces acceptable emulsions with minimal difficulty

Lower internal phase volume

The use of (lower/higher) internal phase volume makes it more difficult to avoid creaming or sedimentation

Hydrophilic colloids

A lower internal phase volume can be corrected by increasing the consistency of the external phase by addition of ___________________

High

The use of very HIGH internal phase volume tend to produce (low/high) viscosities, and thus it requires special manufacturing processes

W/O Emulsions

Phase volume ratio changes may also lead to Phase inversion. Phase inversion is more possible with __________ emulsions

Natural Emulsifiers

Influence emulsification by acting as hydrophilic colloids / Increase viscosity of the aqueous phase

Tragacanth, Acacia, Pectin, Alginates, Starch

Plant-Based Emulsifiers (5)

Gelatin, Casein, Egg Yolk, Wool Fat (Lanolin), Cholesterol

Anima-Based Emulsifiers (5)

Finely divided solids

Influence emulsification by its tendency (by polar solids) to be wetted by water and (by non-polar solids) to be wetted by the oil phase

Finely divided solids

Shown to be good in combination with synthetic or plant-derived emulsifiers

Finely divided solids

Since the polar or non-polar solid appears to exist as a fine colloidal layer, acting as an interfacial barrier to promote flocculation

Bentonite, Veegum

Colloidal Clays (2)

Mg(OH)2; Al2(OH)3; Trisilicates

Metallic Hydroxides (3)

Synthetic emulsifiers

Promote emulsification by its adsorption at the oil-water interface as a monomolecular phase

Sodium lauryl sulfate

Anionic Synthetic emulsifier (1)

Benzalkonium chloride

Cationic Synthetic emulsifier (1)

Spans, Tweens, PEG400

Non-ionic synthetic emulsifiers (3)

Hydrophile-lipophile balance value (HLB Number)

It is assigned to an emulsifier depending on its relative polarity

Hydrophile-lipophile balance value (HLB Number)

It is the percentage weight of the hydrophilic group divided by five (5) for non-ionic emulsifiers

Viscosity

Once the derived emulsion and emulsifiers have been chosen, a consistency that will provide the desired stability and flow characteristics must be attained.

Alter the emulsifier concentration

[Procedures that may be adapted to improve/modify consistency] to produce a flocculated system that will remain rigid, until agitated

Alter the phase volume ratio

[Procedures that may be adapted to improve/modify consistency] This is desirable for emulsions. Specially, applicable for parenteral, oral, and topical emulsions

Proper retention of the product on the skin; Proper spreading characteristics

[Procedures that may be adapted to improve/modify consistency] For lotions and creams, greater consistency is required to provide (2)

Spermaceti, cetyl alcohol, stearyl alcohol, beeswax

[Procedures that may be adapted to improve/modify consistency] Addition of long-chain waxes and high MW alcohols, such as _________ (5), to the oil phase to increase the total solids content of the emulsified product.

Addition of thickening agents

[Procedures that may be adapted to improve/modify consistency] Addition of _______ agents to the External phase, but excessive amounts should be avoided to prevent an adverse effect on flow properties.

High concentration

Any preservative distributed in the oil phase, will not be available for antimicrobial activity in the aqueous phase. The remedy is a (high/low) concentration of preservative is required.

Higher amount

If the preservative interacts with any of the emulsion components, then the preservative action will be diminished. The remedy is a (higher/lower) amount/quantity of the preservative is required.

Vegetable oils and hydrocarbon bases

Oxidation of organic compounds readily occur in ________ (2) due to polyunsaturated FA's present in these substances.

Turbulence

Large amounts of air accumulated during the emulsification process

Rancid taste; Unpleasant odor; Darkening of color

Oxidation in emulsions results in ________ (3)

Gallic acid, BHA, BHT, tocopherol and alkyl gellates

Antioxidants used for cosmetics (5)

Guaiacol, pyrogallol, citric acid, glycerin, and benzoin

Antioxidants used for pharmaceutical emulsions (5)

High Speed/Turbulence required in agitation and filling operations; Excess soluble surfactant added in the emulsion formulation

Excess foaming in emulsions: Causes

Regulate the speed of mechanical stirring during the cooling period of the emulsion; Use of compressed air; Use of de-foaming agents such as cetyl alcohol, silicon derivative

Foam control procedures (3)

cetyl alcohol, silicon derivative (Antifoam A, a dimethylsiloxane polymer)

De-foaming agents (2)

Degree of shear, turbulence

The major factors in the preparation of emulsion are (2)

Degree of shear

Splitting of emulsion into tiny droplets

Turbulence

Agitation required to the given dispersion of droplets

Mechanical stirrers

[Equipments used in the preparation of emulsions] Emulsions are stirred by means of various impellers mounted on shafts, which are placed directly into the system to be emulsified.

Mechanical stirrers

[Equipments used in the preparation of emulsions] These equipment are ideal for slow mixing of finished emulsions which have been prepared by melting the waxes

Homogenizers/Colloid mills

[Equipments used in the preparation of emulsions] The high shearing stress produced at pressures ranging from 500-1000 PSI can produce extremely fine droplets depending on the viscosity and interfacial tension of the system.

Ultrasonifier

[Equipments used in the preparation of emulsions] The use of this equipment will produce extremely fine particles for moderately viscous emulsions: The equipment is not available for commercial scale

Emulsion stability

It implies consumer acceptance and the acceptance varies with the use of the product

Aerosols

Emulsion type of _______, though completely separated outside, will become acceptable for use, upon shaking the container before using

Stability, Appearance, function of the final packaged product

Evaluation of emulsion properties and stability

Shake well Label

This label is important to eliminate creaming and sedimentation in fluid emulsions and will make the product acceptable for use

Subsidence

Other term for phase separation

Phase separation/Subsidence

The rate and extent of phase separation is observed by allowing an emulsion to stand in the container