MPharm Surface Tension & Surfactants PDF

MPharm Programme Surface tension & surfactants Dr Paul Carter Slide 1 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Interface Definition: An interface is the transition region wher...

MPharm Programme Surface tension & surfactants Dr Paul Carter Slide 1 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Interface Definition: An interface is the transition region where two immiscible phases contact each other i.e. the contact area between two phases e.g. Liquid-vapour (‘gas’) interface (e.g. liquid surface in air) liquid-liquid (e.g. emulsion) solid-liquid (e.g. suspension) solid-vapour (e.g. solid surface in air) solid-solid (e.g. solid mix) phase one is ~ air Where one phase is liquid and the other gaseous = ‘surface tension’ Where both phases liquids = ‘interfacial tension’ Between solids, physical phenomena such as adhesion and friction. Slide 2 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  oil-water Interface i spontaneously mixed Surface Tension small oil droplets SHAKE are dispersed in water Interfacial Tension Liquid – liquid interface Gas – liquid interface Slide 3 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Surface free energy Excess energy the surface has compared to the bulk Surface molecules have higher energies and reactivities to the => unstable same molecules in the bulk Why? Think about attractive forces on molecules at surface and in bulk – different. strong forces between the molecules => tension & surface gradually deeps down ↓putof ~ energy ~ reducing its energy Nature acts to attain a state of minimum total free energy (more stable). Since the surface has higher energy than the bulk, reducing surface area an efficient way of reducing energy Slide 4 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Surface free energy Water droplets are spherical (smallest surface area for given volume). Occurs spontaneously to reduce energy. Solids can’t deform though! Higher surface area = more reactive. Higher energy. For solids, reducing particle size (milling) creates a increased surface area and therefore more surface free energy. Fine particles are very difficult to handle. To increase surface area of a solid/liquid, energy must be supplied. Example – emulsion formation. Slide 5 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Surface tension Surface of water demonstrates a ‘skin’ that resists puncture Inward force experienced by surface molecules creates a tendency for surface to contract. Slide 6 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Exaggerated diagram - Cohesive forces between molecules in bulk are shared with all neighbouring molecules. On surface, no molecules above – net pull downwards. Surface molecules exhibit stronger attractive forces between them on the surface Slide 7 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Surface tension Surface molecules have higher energy and experience an inward pull. Leave surface and enter bulk – dynamic equilibrium. Typical lifetime of a molecule at the surface is 1 microsecond (1 x 10-6 s) Definition: surface tension is the force acting parallel to the surface and at right angles to a 1m line drawn anywhere in the surface (N m-1) force/area ↑ If area of surface/interface is to be increased, energy must be supplied Definition: surface free energy is the work required to increase the surface area isothermally and reversibly by 1 m2 (J m-2) 1 Surface tension and surface free energy are numerically equivalent Slide 8 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Surface tension Surface free energy and surface tension have symbol with subscript referring to system e.g. w/a So, liquid/vapour surface tension = l/v interfacial free energy of an o/w system = o/w V The surface tension of water is 72 mN m-1 at 250C. um u ↓ The surface tension of water decreases significantly with ↑ in temperature increase Slide 9 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Surface tension versus temperature Approximately linear. Hot water better cleaning agent than cold – a lower surface tension makes hot water a better ‘wetting agent’ to get into pores/fissures rather than bridging them (with surface tension effect). Soaps/detergents further lower the surface tension 70 Surface tension (mN m-1) 60 (59 mN m-1) 50 20 40 60 80 100 Temperature 0C Slide 10 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Surface tension values l/v (mN m-1 at 250C) water 72 glycerol 63 ethanol 22 octanol 27 liquid paraffin 35 mercury 480 Note: presence of impurities reduces surface tension Slide 11 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Wetting phenomena – solid liquid interface hydrophobic hydrophilic Float on surface SINK !! Slide 12 of24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Contact angle No wetting Absolute wetting = 0o =180o contact angled wettability + H dissolution & somereading < 90o = 90o > 90o Slide 13 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Measurement of surface tension Wilhelmy Plate Thin, rectangular plate (glass, mica) attached to a torsion balance, dips into liquid under investigation F vapour 00 liquid Slide 14 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Wilhelmy plate Force, F, to detach plate is calculated. The force of surface tension ( l/v) acts around the perimeter, P. Must be completely wetted i.e. zero contact angle to ensure surface tension act vertically. l/v = F/P Absolute method i.e. no correction factor May use in static mode to measure change in force to keep plate at constant depth – useful when measuring change in surface tension with time or other variable. Slide 15 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Calculation example The force needed to detach a Wilhelmy Plate from liquid A at 200C was 3 mN. The rectangular plate was 2.2 cm length and 2.5 mm thickness. Calculate the surface tension of A at 200C in mN m-1. Give answer to 2 d.p. l/v = F/P F = 3 mN, convert dimensions to metres: Length = 0.022 m, thickness = 0.0025 m. Perimeter = 0.049 m -e(l wh + Therefore, 3/0.049 = 61.22 mN m-1. Slide 16 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  du Nouy tensiometer (ring method) measures force to detach a platinum ring from surface/interface Slide 17of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  du Nouy tensiometer Detachment force = surface tension x perimeter F = 2 (R1 + R2) R1 and R2 are the inner and outer radii for the ring Zero contact angle needed. Cleaning and flaming. During detachment, all forces do not act vertically and therefore need correction factor for accurate determinations (in lab – use apparent surface tension) Slide 18 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  What are surfactants? SURFace ACTive AgenNT A substance which has both water loving and oil loving structural components in the same molecule Slide 19 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Surfactants Amphipathic Hydrophobic group (usually a carbon chain) – no affinity for non-polar aqueous solvents Hydrophilic group – affinity for water loxygen charged Because surfactants have two regions, once in solution they will orientate at surface/interface with hydrocarbon group away from aqueous phase Slide 20 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Surfactant structure out pushedthe Y from phase aqueous ↓ oily Hydrophobic ( lyophilic, Hydrophilic ( lyophobic, water-fearing ) tail water-loving) head containing a containing a charged um hydrocarbon chain functional group Slide 21 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Surfactant action The longer the chain, the more energetically favourable to adsorb at surface/interface. The longer the chain, the greater the tendency to escape the aqueous environment. Traube’s rule = for dilute solutions of a homologous series of the aliphatic alcohols, e.g. CnH2n+1OH, the ratio of the concentration at the surface layer to that in the 4 by a factor of approximately 3 for each additional –CH2 group bulk increases This adsorption lowers surface tension – surface active molecules replace water ↑ molecules - disruption of the water-water bonding. Reduces contractile nature and ↓ surface tension. Dynamic equilibrium therefore reduces Water-water attractive forces > water-hydrocarbon attractive forces > hydrocarbon-hydrocarbon attractive forces cause Slide 22 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Liquid/Liquid interface V A colloidal system comprised of two or more immiscible liquids is called an Emulsion. In cosmetics, as one phase is usually water, they are called water-in-oil or ( oil-in-water emulsions. cause > - may coalescence should be kept suspended shelf life. the during Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Surfactant action Surfactants used as emulsifying agents, detergents, solubilizing agents, wetting agents, foaming & antifoaming agents, flocculating agents Example – liquid paraffin & water emulsion Initially, spontaneous separation of oil & water – reduce interfacial free energy (area of interface) – oil floats since less dense o o w w Shaking gives temporary emulsion. Oil droplets dispersed in water – large increase in interfacial area. High energy situation = unstable. When stop shaking, system reverts spontaneously back to give lowest interfacial area. So how can we form a stable o/w emulsion? Slide 23 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Example – liquid paraffin & water emulsion Add surfactants to form stable system Water soluble surfactant e.g sodium dodecyl sulphate Oil soluble surfactant e.g. cetostearyl alcohol Form mixed monolayer – droplets very small (due to reduction in surface tension). Tendency to coalesce is reduced since complex stable film, that is charged (- ve). Slide 24 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations  Example – liquid paraffin & water emulsion The overall effect is that the interfacial tension between the phases is reduced. Which means that with AB now lower, the work needed to create a surface is less. a ↓ increase V With a surfactant on the surface of the internal particles, they can act as a barrier to coalescence, either by steric hindrance or electrostatic repulsion Slide 24 of 24 MPharm Surfactants and Their Use in Pharmaceutical Preparations Manufacture and cost Manufacture Cost  easy process and bulky  excipients cheap  need pharmaceutical-grade water  drug potentially expensive Partition, dissolution and drug absorption  drug has to cross the lipid membrane of the gastrointestinal tract (permeation)  partitioning: distribution of a molecule between an aqueous and lipid phase  when drug in aqueous solution is adjacent to a lipid environment — drug will distribute itself between the two phases according to its lipophilicity/ hydrophilicity  ratio of equilibrium concentration in oil and water is the partition coefficient — highly dependent on ionisation state of molecule — very low partition coefficients when ionised and higher values when they are unionised — very strong link between partition and pH of aqueous phase Drug dissolution  solubility is the equilibrium value of saturated concentration  dissolution is the process by which a drug dissolves Surfactants Surfactants are surface-active molecules which accumulate at surfaces  are amphipathic/ amphiphilic molecules: contain two separate regions — hydrophilic — hydrophobic  polar head group of surfactant is covalently bonded to non-polar part whereas counter-ion is not  many drugs have surface activity e.g. certain antihistamines, antidepressants, analgesics, anti-bacterials, local anaesthetics  used as excipients to produce many medicines  common in nature e.g. lecithin is extracted from egg, bile salts  commonly used in daily life e.g. soap, washing up liquid, shampoos surface-active drugs — e.g. chlorpromazine, amitriptyline, tetracaine, etc surface-active excipients — e.g. sodium dodecyl sulfate, benzalkonium chloride, sorbitan monolaurate, etc Characteristics Examples Anionic used in greater volume than any other Polar headgroups examples: sodium stearate class of surfactant due to ease and low Carboxylate (COO2-), sulphate (SO42-), sodium dodecyl sulphate cost of manufacture. Used in most sulfonate (SO3-), phosphate (PO43-) sodium cholate detergent formulations Usual counterion: Na+ sodium lauryl sulphate Cationic Usual counterion: halide or methyl sulphate hexadecyltrimethylammonium bromide dodecylpyridinium chloride quaternary ammonium pyridinium cetrimide BP (0.1-1%) cetrimide emulsifying wax benzalkonium chloride Non-ionic Least toxic Polar headgroups examples: heptaoxyethylene monohexadecyl ether sorbitan Polyether or polyhydroxyl group monostearate sorbitan esters polysorbates cetomacrogol 1000 Zwitterionic Usual counterion: N-dodecyl-alanine glycine NH2-CH2-COOH +ve : almost invariable NH4+ aminopropionic acid NH2-CH2-CH2-COOH -ve : vary but COO- is the most common betaine  At a liquid/ air interface At oil-water interface Adsorption at liquid/air interface. Hydrophobic region of Adsorption at interface between aqueous and non-aqueous molecules escapes from hostile aqueous environment. liquids. Hydrophilic headgroup goes in aqueous phase. Surfactant molecule orientates itself to remove its Hydrophobic tail goes in the oil/non-aqueous phase. hydrophobic part from water. At liquid/ Hydrophobic solid interface Micellisation - micelle formation Surfactants adsorb onto surface, which reduces contact Molecules are arranged in spheroidal aggregates with between hydrophobic groups and water; This allows hydrophobic areas shielded from water by mantle of attainment of minimum energy state. hydrophilic groups. Surface tension  molecules at surface of liquid are not completely surrounded by other like molecules compared to those in bulk  net inward force of attraction exerted on surface molecule by bulk molecules  tendency for surface to contract. Surface tension of liquid (  ) defined as: work required to increase surface area by 1 m2 W =  ∆A work expended by force of one newton through distance of one metre i.e. 1 J = Nm Impact of surfactant on surface tension  surfactant adsorbed at solution/air interface  some water molecules replaced by surfactant molecules  force of attraction between bulk water molecules and surfactant molecule is less than water-water attraction  contracting power of the surface is reduced  surface tension is reduced Impact of surfactant on interfacial tension aqueous and non-aqueous liquids Solid / Liquid interface  interfacial tension is generally between surface tensions of two  solid surface has surface energy immiscible liquids, except where there is attraction between them  as a result, solid/liquid interfacial tension decreases  surfactant migrates to interfacial layer, so interfacial tension is  when surfactant reduces interfacial tension at reduced solid/liquid interface, solid can be wetted (liquid  surface/interfacial tension of aliphatic hydrocarbon–water is higher has spread over its surface) than hydrocarbon-aqueous surfactant solution In Pharmacy, wetting is important for drugs to be suspended or dissolve when pharmacists are making medicines or for a drug to be dissolved in the body, so that it can be absorbed and act General types of Adsorption — Physical adsorption – adsorbate is bound through weak Vander waal’s forces — Chemical adsorption – chemisorption – which involves stronger forces e.g. ion-exchange process