Week 13 Emulsions & Creams 2024 PDF

Pharmacy (PHA114) Emulsions & Creams Dr Paul Carter  Emulsions Low viscosity disperse systems – (% w/v) – O/W or W/O – External application, Two immiscible phases + appropriate amount of emulsifier (≤ cmc) WEEK ? What is an emulsion?...

Pharmacy (PHA114) Emulsions & Creams Dr Paul Carter  Emulsions Low viscosity disperse systems – (% w/v) – O/W or W/O – External application, Two immiscible phases + appropriate amount of emulsifier (≤ cmc) WEEK ? What is an emulsion? An emulsion is a type of colloid. Colloids are macro-heterogeneous systems that are comprised of one substance dispersed in another. They are not solutions, the dispersed particles do not dissolve, but instead are dispersed or suspended through another substance. The dispersed particles may have at least one dimension in the order of 10-9m to 10-6m (1- 1000nm) which is too small to see without a microscope. WEEK ? What is an emulsion? The dispersed substance is called the dispersed or internal phase, the material Internal phase it is dispersed in is called the continuous or external phase. Depending on the physical state of the internal and external phases, Continuous phase determines the type of colloid. An emulsion is a liquid dispersed in another liquid WEEK ? Instability of Emulsions Once the water and oil have separated out, the substance is no longer an emulsion. ‘Emulsion Stability’ describes the length of time a mixture remains an emulsion before it separates out. To understand ‘emulsion stability’ we must first discuss what makes an emulsion unstable. – Thermodynamic instability – Kinetic instability WEEK ? Thermodynamic Instability - ∆A ∆A is the surface area between two surfaces. In this case between the oils and water. To create an emulsion requires a large increase in surface area between the two phases. Therefore ΔA is always positive and large for emulsification or negative and large for separation. WEEK ? Thermodynamic Instability - ΔA and ɣAB ΔA and ɣAB together represent the forces that need to be overcome to create an emulsion. To explain, energy is required to overcome the interfacial tension between the phases. And, once the interfacial tension is overcome, more energy is required to create more surface area between the phases. Together ΔA and ɣAB represent the work needed (W) to create an emulsion with a certain droplet size, expressed in J. WEEK ? Kinetic Instability There are 4 + 1 processes of Kinetic instability: WEEK ? Kinetic Instabilty WEEK ? Kinetic Instability – Creaming and Sedimentation Creaming and Sedimentation are vertical process and are related: Creaming: This occurs when the dispersed particles are not as dense as the continuous phase and they tend to rise to the surface. Sedimentation: Similar to creaming except for the fact the dispersed phase has a higher density compared to the continuous phase. The particles tend to settle to the bottom of the container under gravity and remain as discreet entities. WEEK ? Kinetic Instability – Creaming and Sedimentation Sedimentation and Creaming occurs due to gravity. A difference in density between the phases will result in the less dense phase migrating above the more dense phase. This results in an increase in concentration of the internal phase at the surface (creaming) or bottom (sedimentation). Its rate was described by Stoke’s Law: Where V is the velocity of dispersed phase particle i.e. rate of sedimentation and creaming, r is the radius of the particle and g is the acceleration due to gravity. μ is the viscosity of the continuous phase, ρC and ρD are the respective densities of the continuous (C) and dispersed phases (D). WEEK ? Kinetic Instability – Creaming and Sedimentation What does Stokes Law tell us?? If we have a creaming or sedementing formula what does Stokes Law tell us we can do? Size of internal phase particle is important – as particle size increases, rate of sedimentation or creaming increases as well. So for increased stability the smaller the particle size the better. Hence, any flocculation or coalesces will have an effect on rate of sedimentation or creaming. Differential between the density of the internal and external phases should be small, if there is a large differential in density the rate of creaming and sedimentation will also be large. Rate of creaming and sedimentation is inversely proportional to viscosity of the continuous phase. As viscosity increases, the rate of creaming or sedimentation decreases. Viscosity is dependent on many things, including for most fluids, temperature. Formulation and CSC 201 Slide 12 Quality by Design of WEEK ? Kinetic Instability – Coalescence and Flocculation Coalescence and flocculation occur due to collisions of the dispersed phase droplets. These collisions can result in – repulsion, droplets move apart again with no change to the colloidal state. – Coalescence, where the droplets join to make a larger droplet, decreasing overall surface area of the colloid, or – flocculation, where the droplets do not move apart but associate and move together through the colloid but overall surface area remains the same. WEEK ? Disproportionation Disproportionation is a process – often referred to as Ostwald ripening – that is dependent on the diffusion of disperse phase molecules from smaller to larger droplets through the continuous phase. It is driven by the phenomenon that smaller droplets have a higher internal pressure than larger droplets. As expressed in the Laplace equation: where, P is the Laplace pressure (diff in pressure between inside and outside), γ is the surface tension and r is the droplet radius. WEEK ? Stabilising Methods - Emulsifiers Emulsifiers are surface active ingredients (surfactants) that migrate to the interface between the two phases. They have two affects on the system: – Lowering the interfacial tension between the phases. – Creating repulsive forces between the internal phase particles to retard the rate of coalescence and flocculation. Formulation and CSC 201 Slide 15 Quality by Design of WEEK ? Stabilising Methods - Emulsifiers – Creating a physical barrier to coalescence and flocculation by extending into the continuous phase. This stops collision by entanglement of the molecules. WEEK ? Stabilising Methods - Emulsifers Emulsifiers create a repulsive force by: – Creating a surface charge on the surface of each droplet. This creates a electrostatic charge on the particles and the creation of an electrical double layer. Slide 17 WEEK ? Stabilising Methods – Zeta potential Crucially, as the particle moves through the continuous phase, the outer portion of the diffuse layer is in flux beyond the slipping plane. Meaning that the whole double layer still has an electric potential that extends into the continuous phase. This is commonly referred to as the Zeta potential. The higher the Zeta potential the more repulsive the particles are to each other – stabilising the system. WEEK ? Zeta Potential As a generalisation a ±30 mv is often cited as the threshold of colloidal stability (Stubenrauch, C., 2006. Emulsions, Foams and Suspensions. Fundamentals and Applications. By Laurier L. Schramm: Wiley Online Library). Above ±30 mv and the particles repel each other enough to maintain colloidal stability and below the repulsion is not enough to prevent particle collision. Remember this is only a measure of stability with respect to coalescence and flocculation.  Emulsion rheology η = ηo (1 + 2.5 φ) Where: η = viscosity of emulsion ηo = viscosity of continuous phase φ = phase volume  Factors that affect the type of emulsion HLB of the emulsifying system Relative amount of the two immiscible phases (phase volume φ) – Phase volume φ is the %volume of disperse phase = (volume of disperse phase / total volume of emulsion) x 100 – w/o emulsions: volume of oil phase > volume of aqueous phase ϕ = 30-40% – o/w emulsions: ϕ up to 60%  Effect of emulsifier on emulsion type Bancroft rule: the liquid that the emulsifier is more soluble in, becomes the continuous phase. – Ionic surfactants and surfactants with strong polar heads (HLB = 8-16) stabilise o/w emulsions – Surfactants with long hydrocarbon tails and non-ionic less polar heads (HLB = 3-6) stabilise w/o emulsions  Effect of emulsifier on emulsion stability Mixture of surfactants – A binary mixture of surfactants with high and low HLB gives a more stable emulsion than a single surfactant – Formation of a complex interfacial film – mixed monolayer Compatibility between the surfactants!  Formulation of emulsions using the HLB system A mixture of two surfactants, with low and high HLB values, gives a more stable emulsion than a single surfactant alone. HLBmixt = x.HLBa + y.HLBb What is the overall HLB value of a surfactant mixture containing 25% Span 20 and 75% Tween 20? (HLBSpan 20 = 8.6 & HLBTween 20 = 16.7)  Formulation of emulsions using the HLB system A series of five emulsions (i to v) have been prepared using 35% mineral oil, 60% water and 5% emulsifier system with varying compositions. Table 1 shows the HLB value and mean globule size of each emulsion. Which is the most stable emulsion? Emulsion i ii iii iv v Mean globule size (μm) 28 20 15 3 25 HLB mixt 15 13 12.5 11 7  Creams Semi-solid emulsions for external application – Two immiscible liquid phases (oily and aqueous) – Emulsifying agent o/w- “vanishing creams” – Washable, cooling action – Classified according to surfactant used (non-ionic, anionic, cationic) w/o- oily creams – Emollient and cleansing action – Less greasy than ointments – Contain lipophilic emulsifying agents e.g. wool alcohols  Creams High viscosity – Semisolid emulsions (% w/w) Structured systems containing: – Excess emulsifier Gel crystalline phase or liquid crystals (>> cmc) – “Self-bodying” ingredients e.g. waxes Semi-solid consistency Micelles & Critical Micelle Concentration (cmc) Surfactant (surface active) molecules accumulate (adsorb) at the interface of two immiscible phases and form an adsorbed monolayer. Critical Micelle Concentration (cmc) – The concentration at which the adsorbed monolayer becomes saturated with surfactant molecules. Any additional surfactant molecules will form micelles. Micelles – Spherical aggregates of surfactant molecules in an aqueous solution Adsorbed monolayer Micelle  Formulation principles of emulsions & creams Type of emulsion/cream depends on: – Relative amount of the two phases – Type of surfactant added (see Bancroft’s rule!) Susceptible to microbial growth in the aqueous phase – Manufacture under aseptic conditions – Antimicrobial preservatives (e.g. phenoxyethanol, parabens, chlorocresol, benzoic acid, cetrimide etc) Antioxidants – Prevent oxidation of oily phase  Preparation methods of emulsions & creams “Solution method” – Each surfactant is dissolved in the respective phase. – The two phases are mixed and according to HLBA+B an o/w or w/o emulsion is formed. “Dispersion method” – Surfactant is dispersed in the phase that is less soluble in, then mixed slowly with other phase. – Gradual phase conversion. The resultant continuous phase is the one that the surfactant is more soluble in. (See Bancroft rule) Or – The emulsifying wax is dispersed in the oily phase, then the aqueous phase is gradually added at the same temperature.  Clotrimazole cream B.P. Clotrimazole dispersed in an o/w cream base – Cream base: Sorbitan monostearate polysorbate 60 cetyl esters wax cetostearyl alcohol 2-octyldodecanol purified water benzyl alcohol What is the role of each excipient?  SUGGESTED READING Eccleston G., 2017. Emulsions and creams. In: Aulton M.E. & Taylor K.M.G. (Eds.), Aulton’s Pharmaceutics; The design and manufacture of medicines, Elsevier, 5th edition. Chapter 27.