Emulsions and Creams Detailed Notes

Emulsions and Creams

Learning Outcomes

• Calculate the Required Hydrophilic-Lipophilic Balance (RHLB) for emulsions and the quantity of surfactant to use.
• Discuss the stability of emulsions and methods for stability testing.
• Discuss the role of other ingredients in emulsions.
• Discuss the preparation methods for emulsions.
• Discuss different types of cream bases.
• Discuss the compatibility of drugs and cream bases.
• Discuss preservation considerations for emulsions and creams.

Formulation of Emulsions

• Developing an emulsion formulation requires considering several factors:
  • Type of emulsion required (e.g., oil-in-water or water-in-oil).
  • Required route of administration (e.g., oral, IV, topical).
  • Volume of the internal phase.
  • Desired droplet size and consistency.

Emulsion Types and Formulation Considerations

• Emulsion Type:
  • Oral and IV routes typically use oil-in-water (o/w) emulsions.
  • Topical applications can use either o/w or water-in-oil (w/o) emulsions.
• Volume of Internal Phase:
  • Affects emulsion stability; too high a volume can lead to phase inversion.
• Droplet Size and Viscosity:
  • Reducing droplet size decreases the rate of creaming.
  • Viscosity influences emulsion stability; higher viscosity may be needed for cream spreading.

Hydrophilic-Lipophilic Balance (HLB) System

• The HLB system is used to select mixtures of emulsifying agents to produce physically stable emulsions.

HLB Values

• o/w emulsifiers generally have HLB values between 8 and 16.
• w/o emulsifiers generally have HLB values between 3 and 6.

Selection and Concentration of Emulsifying Agents

• An emulsifier is an essential ingredient in an emulsion.
• Often, a mix of emulsifiers is used to produce a stable emulsion.
• Mixing two emulsifiers together can achieve a required HLB (RHLB).
• The HLB value for each emulsifier is used to determine the proportion of each emulsifier needed to achieve the required HLB.

Calculation Example

• Prepare an o/w emulsion with the following composition:
  • Cottonseed oil: 30%
  • Stearyl alcohol: 3%
  • Beeswax: 2%
  • Emulsifier: qs (quantity sufficient)
  • Water: to 100%

RHLB Calculation Example

• Look up the RHLB for each oil.
• Calculate what fraction of the total oil each represents (Total oil = 30 + 3 + 2 = 35).

Emulsifier Mixture Calculation Example

• Use Span 60 (HLB = 4.7) and Tween 60 (HLB = 16.49).
• Mix these to produce the RHLB of 10.49.
• If preparing 100g of this emulsion with 2% emulsifier, what would be the actual amounts of Span 60 and Tween 60 you would use?
• Equation: Y \times 4.7 + (1-Y) \times 16.49 = 10.49
• Solve for Y: Y = 50.9\%%
• Therefore, 50.9% Span 60 and 49.1% Tween 60 are required.
• Total amount of emulsifier: 100 \times 2\%% = 2g
• Span 60: 2 \times 50.9\%% = 1.02 g
• Tween 60: 2 \times 49.1\%% = 0.98 g

Stability of Emulsions

• A stable emulsion retains droplets in their initial character and uniformly distributed.
• Cracking: Separation of the emulsion into two phases.
  • Factors that can lead to cracking:
    • Adding a chemical incompatible with the emulsifying agent (e.g., anionic + cationic).
    • Bacterial growth.
    • Temperature change (heat or cold).
    • Poor formulation.

Breakdown of Emulsions

• Creaming
• Sedimentation
• Flocculation
• Phase inversion
• Coalescence
• Ostwald ripening

Flocculation and Coalescence

• Flocculation:
  • Loose associations, re-disperse easily.
• Coalescence:
  • Fusion of droplets to make larger droplets; irreversible process.

Creaming and Sedimentation

• Many emulsions cream on standing (e.g., some milk products).
• Droplets do not coalesce, redisperse easily.
• Gives an inelegant product and possibility of inaccurate dose.
• Increases likelihood of coalescence.
• Minimize by:
  • Enhancing viscosity of external phase.
  • Reducing the size of droplets to very fine with a homogenizer.
  • Adjusting the densities of both internal and external phases to be the same.

Ostwald Ripening

• Results from the finite solubility of the liquid phase.
• Immiscible (oil and water) does not mean that there is no solubility.
• Emulsions are poly-disperse, and smaller droplets are likely to dissolve into the bulk.
• Become deposited on larger droplets.
• Larger droplets grow in size.

Phase Inversion

• o/w inverts to w/o.
• w/o inverts to o/w.
• Phase volume ratio contributes to the emulsion type produced.
• Contributes to stability.
• Any additive that alters the HLB of the emulsifying agent may alter the emulsion type.
• Adding a magnesium (Mg) salt to an emulsion stabilized with sodium oleate will cause the emulsion to crack or invert.

Assessing Stability

• Evidence of cracking.
• Look for creaming, sedimentation.
• Look at change in droplet size with time.

Preparation of Emulsions

• Small Scale:
  • Dry mortar and pestle.
  • Mechanical blender or mixer.
  • Hand or bench-type homogenizer.
• Large Scale:
  • Large mixing tanks with a high-speed impeller.
  • Product may be rendered finer by:
    • Passage through a colloid mill, in which the particles are sheared between the small gap separating a high-speed rotor and the stator.
    • Passage through a large homogenizer, in which the liquid is forced under great pressure through a small valve opening.

Extemporaneous Preparation: Mortar and Pestle Method

• Primary Emulsion Formation:
  • Fixed oils (vegetable oils, mineral oil): 4:2:1 oil: water: gum (Acacia).
  • Volatile and essential oils: 3:2:1 or 2:2:1.
• Dry gum method.
• Wet gum method.

Extemporaneous Preparation: Wet and Dry Gum Methods

• Wet Gum (English) Method:
  • Mucilage made by mixing acacia and water.
  • Oil is added slowly with rapid mixing to form the primary emulsion.
  • More water is then added and triturated rapidly until complete.
• Dry Gum (Continental) Method:
  • Acacia mixed with oil for a short time.
  • Water is added all at once to make the primary emulsion with rapid trituration.
  • When a snapping sound is heard, the primary emulsion is formed.
  • More water is added and triturated until complete.

Other Methods of Emulsion Preparation

• Bottle Method:
  • Can be used for volatile and non-viscous oils.
  • Emulsifier + oil placed in bottle and shaken.
  • Requires water added and shaken rapidly to produce primary emulsion.
  • Then add any further additional water, shaking after each addition.
• In-situ Method:
  • Emulsifying agent is made in situ by chemical reaction between fatty acid in the oil phase and a base in the aqueous phase.
  • Emulsion type depends on the type of soap formed.

Ingredients in Emulsions

• Vehicle:
  • Type of water (e.g., oral or IV).
  • pH control?
  • Oil phase - what is the use? (e.g., IV, oral, or topical).
• Antioxidants?
  • Oil or water phase: if the oil phase, use oil-soluble antioxidants such as BHT, BHA, propyl gallate.
• Flavors and sweeteners - if oral.
• Viscosity enhancers: Physical stability but also the product must be usable! (not too viscous and won’t pour or spread).
• Emulsifying agent: oral, external, or parenteral?

Preserving Emulsions

• Particularly critical for o/w emulsions.
• Prevent degradation of product, odor changes, color changes, gases.
• Prevent degradation of emulsifier.
• Other ingredients can also provide a medium for microbe growth.
  • Arachis oil supports Aspergillus species.
  • Liquid paraffin supports Penicillium species.

Preservatives for Emulsions

• Must be able to partition into the oil phase.
• Reduce concentration in water phase.
• Need to achieve appropriate concentration in the water phase.
• May also complex to other ingredients or sorb into the container.
• Common preservatives: Benzoic acid, Parabens, Chloroform, Chlorocresol, Phenoxyethanol, Benzyl alcohol, Quaternary ammonium compounds (cetrimide- also emulsifier), Organic mercurial compounds (phenylmercuric nitrate), Sorbic acid and its salts.

Desirable Features of Preservatives

• Wide spectrum of activity.
• Bactericidal rather than bacteriostatic.
• Not toxic, irritant, sensitizing.
• High water solubility and low partition coefficient.
• Compatible with other ingredients.
• Stable over a wide range of pH and temperature.
• Free from color or odor.
• Retain activity in the presence of a large number of microorganisms.

Creams

• Semi-solid preparations, usually emulsions intended for application to the skin.
• Oil miscible (w/o) called OILY creams.
• Water miscible (o/w) called AQUEOUS creams.

Oily Creams

• Protective and emollient.
  • Examples: Oily cream, Cold Cream, Oily Glycerol Cream.
• Not suitable for the presentation of water-soluble antiseptics.
• Used for local protective agents such as calamine, zinc oxide and applying oil soluble medicaments such as menthol, methyl salicylate.

Calamine Cream (Oily)

• Calamine
• Oleic acid
• Phenoxyethanol
• Arachis oil
• Wool fat
• Calcium hydroxide solution
• Used as antipruritic/protective agent.

Aqueous Creams

• Used to deliver medicaments to the body surface.
• o/w easily removed by washing.
• Used for water-soluble antiseptics, local anesthetics, or other dermatological agents.
• Water may reduce the stability of medication which readily hydrolyzes.
• A preservative should be used to reduce microbial growth.
• Classified according to the type of emulsifier used:
  • Anionic (- charge), cationic (+ charge), and non-ionic.

Anionic Cream

• Aqueous cream
• Emulsifying ointment
• Chlorocresol
• Purified water
• Emulsifying ointment contains sodium lauryl sulfate and cetostearyl alcohol and liquid paraffin.

Cationic Cream

• Cetrimide cream
• Cetrimide
• Cetostearyl alcohol
• Liquid paraffin
• Purified water

Nonionic Cream

• Cetomacrogol cream (Sorbolene)
• Cetomacrogol emulsifying wax
• Liquid paraffin
• Chlorocresol
• Glycerol
• Water
• Cetomacrogol emulsifying wax contains cetomacrogol 1000 and cetostearyl alcohol.

Selecting a Cream Base

• If a cationic drug is used, do NOT use an anionic cream.
  • Cationic substances: Alkaloidal salts, most local anesthetics, most antihistamines, sympathomimetic amines such as adrenaline salts, acriflavine, atropine sulfate, benzalkonium chloride, cetrimide, PMN, promethazine HCL, procaine HCl.
• If an anionic drug is used, do NOT use a cationic cream.
  • Anionic substances include: Sodium alkyl sulfate, acid dyestuffs, soluble barbiturates, soluble sulphonamides, soluble organic mercurial antiseptics.
• When in doubt of the nature of the therapeutic agent, recommend the use of a NONIONIC cream.
• Sorbolene (also called cetomacrogol) cream.