Emulsion and Formulation of Emulation Industrial Pharmacy

Definition: Emulsion is a thermodynamically unstable mixture of two immiscible liquids in which miscibility is supported by Emulsifiers.

Emulsion consist of two phases or part alongside with emulsifier. One phase is continues phase or external phase, while the other is discontinues phase or internal phase or disperse phase. Disperse phase is in the form of globules and continues phase is the phase in which the globules are present in suspended form. Emulsifiers are the agent which support the emulsion and prevent the separation of two phases (retain the disperse phase in disperse form).

Types of Emulsion: Three type of emulsion. 1) Simple emulsion W/O or O/W. 2) Multiple emulsion which is also called emulsion in emulsion W/O/W or O/W/O. 3) Micro-emulsion is a clear type of emulsion in which the globule size is very low in size 10-75 nm.

Formulation considerations of emulsion:

1)    Choice of oil phase: mainly vegetable oils and mineral oils are used. Mineral oil is most extensively used. In case of topical preparation oils must be viscous in order to form film. Viscosity of oils can be increased by adding agents like waxes (bees wax , carnauba wax) etc. in case of oral preperations vegetable oils are preferred.

2)    Consistency: consistency of emulsion is related to terms like texture or feel , viscosity, and thixotrophy. Viscosity of emulsion is required to give a feel of richness of greasy texture to the emulsion. Viscous emulsion form a thick film upon topical application. But the viscosity should be enough so that it must not prevents the flow from the container. Thixotrophy is a rheological property of emulsion in which upon application of share force the viscosity of emulsion increases. Thixotrophy is required in most cases. The feel or texture of emulsion depends upon the nature of the emulsion o/w or water in oil. W/o emulsions feel greasy and sticky and cant be washed easily while o/w emulsion are less greasy , less sticky and easily washable.

       ways to increase the viscosity of emulsion:

      I.            Reducing the particle size: if the particle size of the disperse phase is reduced then it viscosity will be increased.

   II.            By adding viscosity builders: in O/W emulsion viscosity can be increased through adding tragacanth, CMC, HPMC etc. While in W/O emulsion viscosity can be increased through poly-cations, resins etc.

III.            By increasing internal phase concentration: viscosity of emulsion is directly related to the concentration of the internal phase or ratio of internal phase to external phase. Increasing the internal phase concentration viscosity is proportionally increased.

3)    Choice of Antimicrobials (Preservatives) : selection of preservative used in emulsion depends upon;

• a)    Chemical compatibility with the API and other formulating agents.
• b)    Toxicity inside the body.
• c)     Tissue irritation

Most commonly used preservative are, Phenolics (phenol, benzalkonium chloride, benzethonium chloride),  benzoic acid, sodium benzoate, mercurials, chlorocresol, Alcohol, parabans (methyl parabans and propyl parabens where methyl paraben is water soluble and propyl paraben is oil soluble so for the perfect result a blend is prepared) (note parabens are the poly-hydroxy benzoic acids). Phenolics (phenol).

Methyl paraben is water soluble and propyl paraben is lipid soluble so that both are included to give complete preservation to the emulsion. Instead this combination give synergistic antimicrobial effect so batter protection against microbes.

4)    Antioxidants: Antioxidants are the compounds which are used to prevent oxidation/rancidity of the oil phase of emulsion. Auto-oxidation is the problem with unsaturated oils. Microbial oxidation is also a problem with emulsion. Antioxidants are:

Chain terminators: used particularly in case of autoxidation(which is a chain rxn). Agent used are thiosorbital and thioglycerol. Lipid soluble chain terminators are used which are Butylated Hydroxy- Toluene and Butylated Hydroxy Anisole they have very disturbing smell. Now a days L-tocopherol is widely used instead of them.

Reducing agents:  Reducing agents have capability of accepting electron inverse to oxidation. Agents include are sodium sulphide, sodium metabisulphide, and ascorbic acid.

De-aeration : De-Aeration is the process in which air is removed. N₂ Spurging is used to de aerate the emulsion. Vacuum applied along with Nitrogen spurging completes de-aeration. 

Chelating Agents: Traces elements: which cause oxidation. Trace element induced oxidation can be prevented by EDTA, H₃PO_4, Citric acid and tartaric acid.