Emulsions


Introduction

  • Definition: Emulsions consist of two immiscible liquids where one liquid is distributed as droplets throughout the other. The system is stabilized by the presence of an emulsifying agent (EA).

  • Droplet Size of Dispersed Phase (Internal Phase): Ranges from 0.1 – 100 μm.

Objectives

  1. Understand emulsions as dispersed systems.

  2. Explain the advantages and disadvantages of emulsions.

  3. Understand the formulation of emulsions.

  4. Recognize the different forms and causes of emulsion instability.

Types of Emulsions

Oil-In-Water (o/w) Emulsions

  • Description: Oil droplets are dispersed in a continuous water phase.

  • Properties: Generally non-greasy; suitable for oral and topical applications.

Water-In-Oil (w/o) Emulsions

  • Description: Water droplets are dispersed in a continuous oil phase.

  • Properties: Greasy; used in ointments for occlusive effects.

Emulsifying Agents (EA)

  • Function: Surfactants reduce interfacial tension, stabilizing the dispersion.

  • Solubility Effects:   - If EA is more soluble in water, an o/w emulsion is formed.   - If EA is more soluble in oil, a w/o emulsion is formed.

Advantages of Emulsions

  • Delivery method for drugs that poorly dissolve in water.

  • Masks unpleasant taste of drugs.

  • Reduces skin irritation by trapping drugs in oil droplets (especially in o/w emulsions).

  • Suitable for patients with difficulty swallowing solid dosage forms.

  • Useful in total parenteral nutrition (IV feeding).

Disadvantages of Emulsions

  • Thermodynamically unstable: They can separate or break down over time.

  • Manufacturing Challenges: Difficult to manufacture consistently.

Formulation of Emulsions

Choice of Emulsion Type

  • Oral Formulations:   - o/w for oil-soluble drugs.

  • Topical Formulations:   - o/w for non-greasy effects, easily washed off.   - w/o for greasy, occlusive effects.

  • Parenteral Formulations:   - IV requires o/w; IM can utilize w/o.

Choice of Oil Phase

  • Oral Oils: Liquid paraffin, castor oil, cod liver oil, arachis oil, sesame oil, maize oil.

  • Parenteral Oils: Cottonseed oil, soya bean oil, safflower oil.

  • Topical Oils: Turpentine oil, beeswax.

  • Note: Type of oil depends on the route of administration.

Emulsion Consistency

  • o/w Consistency:   - Less greasy/sticky; easily washed. Often found in lotions.

  • w/o Consistency:   - Greasy texture; not easily washed. Common in ointments.

Ideal Properties of Emulsifiers

  • Compatibility: Does not affect stability or therapeutic activity.

  • Stability: Chemically and physically stable.

  • Safety: Non-toxic and non-irritant.

  • Acceptability: Organoleptically pleasant, effective at low concentrations.

Types of Emulsifying Agents

Anionic Emulsifiers

  • Characteristics: Produce negatively charged ions, often used in external formulations.

  • Examples: Alkali metal soaps (sodium oleate → o/w), divalent/trivalent metal soaps (calcium oleate → w/o).

  • Toxicity: Generally higher toxicity.

Cationic Emulsifiers

  • Characteristics: Produce positively charged ions, incompatible with anionic emulsifiers.

  • Can form o/w emulsions when mixed with non-ionic emulsifiers.

  • Examples: Cetrimide (has antimicrobial activity).

Non-Ionic Emulsifiers

  • Characteristics: Do not dissociate into ions; low toxicity and irritancy.

  • Can be used in both o/w and w/o emulsions.

  • Examples: Sorbitan esters, polyoxyethylene fatty acid derivatives.

Amphoteric Emulsifiers

  • Characteristics: Possess both positively and negatively charged groups.

  • Example: Lecithin.

Naturally Occurring Materials

  • Properties: Variability in batch composition can lead to inconsistencies; susceptible to bacterial or mold growth.

  • Examples: Polysaccharides (acacia), semisynthetic polysaccharides (methylcellulose), sterol-containing substances (lanolin).

Finely Divided Solids

  • Characteristics: Solids preferentially wetted by the aqueous phase will form o/w emulsions; vice versa for w/o emulsions.

  • Examples: Aluminum hydroxide, magnesium hydroxide, bentonite, kaolin (for o/w); talc, carbon black (for w/o).

Antioxidants

  • Purpose: Prevent degradation by oxidation of oils.

  • Examples: Ascorbic acid, citric acid, sodium metabisulfite, sodium sulphite.

Other Ingredients in Emulsions

  • Preservatives: Benzoic acids, chlorocresol, phenoxyethanol.

  • Sweetening Agents: Sucrose, sorbitol, glycerol.

  • Additives: Colors, flavors.

HLB Scale

  • HLB (Hydrophile-Lipophile Balance): Scale from 1 to 20 indicating polarity of emulsifiers.   - High HLB (≥ 10): Suitable for o/w emulsions.   - Low HLB (≤ 10): Suitable for w/o emulsions.

HLB Values of Some Emulsifiers

  • Sorbitan tristearate (Span 65): 2.1

  • Oleic acid: 4.3

  • Sorbitan monooleate (Span 80): 5

  • Beeswax: 12

  • Gelatin: 9.8

  • Cetyl alcohol: 15

  • Polyoxyethylene sorbitan monostearate (Tween 60): 14.9

Calculation Examples for HLB

  1. Calculate HLB value of a mixture:    - Span 60 (HLB 4.7) - 40% and Tween 60 (HLB 14.9) - 60% gives an HLB value of approx 10.8.

  2. Required HLB for a specific o/w emulsion:    1. Determine total % of oil phase.    2. Calculate % of each type of oil.    3. Calculate HLB contribution from each oil.    4. Sum HLB values resulting in a total of 12.1.

  3. Emulsifiers for target HLB:    - Example: For 20 ml of required HLB value of 12.1 using Span 80 and Tween 80, calculate respective volumes resulting in 14.6 ml of Tween 80 and 5.4 ml of Span 80.

Emulsion Instability

  • Types of Instability:   - Flocculation: Aggregation into loose clusters.   - Creaming: Aggregation on top/bottom; reversible by shaking.   - Coalescence: Cracking; irreversible.

  • Causes of Instability:   - Density differences between phases.   - Incorrect selection of emulsifying agents.   - Presence of incompatible excipients.   - Temperature changes.   - Microbial contamination.

Phase Inversion

  • Definition: A phenomenon in liquid-liquid dispersion where the dispersed phase spontaneously becomes the continuous phase and vice versa.

  • Causes: Change in emulsifying agent or phase volume ratio changes. Though the preparation may remain stable, the nature and clinical efficacy of the emulsion may change as a result.