Surfactant Activity - Application PDF

MPharm Programme Surfactant activity & application Dr Paul Carter Slide 1 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Amphipathic Surfactants...

MPharm Programme Surfactant activity & application Dr Paul Carter Slide 1 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Amphipathic Surfactants hydro- Hydrophobic group (usually a carbon chain) – no affinity for aqueous solvents polar CH Hydrophilic group – affinity for water Water – high degree of structure due to hydrogen bonding. If add ionic or strongly polar solute, water structure will be disrupted. But solute can hydrogen bond with water molecules and therefore this compensates for disruption of pure water bonds Ionic and polar materials are freely soluble in water cationic (+ ) lonic 1 anionic 1 Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Surfactants cont. No such compensation for non-polar groups. Solution is resisted. Water molecules need to form extra structured clusters around the non-polar regions. This increased structure results in a negative entropy change. Energetically favourable for hydrophobic groups to withdraw from the aqueous phase. With surfactants, solubility will depend whether polar group sufficiently hydrogen bonds to water to overcome the repulsive effect of the water molecules around the hydrophobic group Because surfactants have two regions, once in solution they will orientate at surface/interface with hydrocarbon group away from aqueous phase. Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Surfactants cont. The longer the chain, the more energetically favourable to adsorb at surface/interface. Higher concentration of more to the surface go on surfactant at surface/interface > - more surface likely to reduce tension This adsorption lowers surface tension – surface active molecules replace water molecules Water-water attractive forces > water-hydrocarbon attractive forces > hydrocarbon-hydrocarbon attractive forces Surfactant molecules at surface cause disruption of the water-water bonding. Reduces contractile nature and therefore reduces surface tension System in dynamic equilibrium Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  HLB The HLB (hydrophilic-lipophilic balance) determines the partition between the two phases and helps us to predict the use of a surfactant. Low HLB = oil soluble, high HLB = water soluble. HLB = %hydrophilic part/5 PHI I I e.g. C10H21(OCH2CH2)6OH non-ionic surfactant oxyethylene Lionic - solubilize anyway Calculate HLB, total mass = 120+21 +(44x6)+17 = 422 * PHI bit % mass X Total mass Hydrophilic part = (44x6)+17 = 281 HLB = (281/422) x(100/5) = 13.3 Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  HLB HLB value use >13 (readily soluble, clear solution) solubilization 8-10 (soluble) o/w emulsification 6-8 (soluble with agitation) wetting 3-6 poor solubility w/o emulsification 1-3 insoluble antifoaming Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  HLB According to the HLB System, all fats and oils have a Required HLB. v requires HLB value of For example: oil phase in formulation Soybean Oil has a required HLB of 7. y Use an emulsifier or blend of emulsifiers that have a HLB of 7 ± 1. So, before we can select our emulsifiers, we must know the required HLB of our oil phase. Start calculating the required HLB of an Oil Phase. Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  HLB Let's suppose that your oil phase (in an emulsion) contains: Soybean (Glycine Soja) Oil = 15% mix usually Cetyl Alcohol = 5% high HLB The total amount of oils in our Oil Phase = 20% + Ow HLB all phase ↓ ↓ Soja) Oil is 75% of the oil phase Therefore Soybean (Glycine and Cetyl Alcohol is 25% of the oil phase. Soybean (Glycine Soja) Oil = 15% of the formula and 75% of the oil phase & Cetyl Alcohol = 5% of the formula and 25% of the oil phase. Required HLB of Soybean (Glycine Soja) Oil is 7 Required HLB of Cetyl Alcohol is 15.5 (75/100) X 7 = 0.75 X 7 = 5.25 overall (25/100) X 15.5 = 0.25 X 15.5 = 3.88 & HLB The required HLB of our oil phase is the sum of these numbers or 9.13 Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Gibbs Adsorption EXAM X TBLO Gibbs derived an equation enabling the extent of surfactant adsorption to be calculated Dynamic equilibrium between surface and bulk molecules – imagine a boundary Surface excess concentration defined as the amount present in the surface phase in excess of that which would have been present if the bulk phase had extended to the surface without change in composition don't Y memorize ! Γ= − (Cb/RT).(dγl/v/dCb) Where Γ = surface excess concentration (mol m-2), Cb = bulk concentration (mol dm- 3), R=gas constant (8.314 J mol-1 k-1), T = thermodynamic temperature (K), dγ /dC l/v b = gradient of surface tension vs bulk concentration at selected value of bulk concentration Verify units? Calculate available surface area per molecule. If Γ=p, NA = avagardos number = 6.023 x 1023 mol-1 1m2 will contain pNA molecules. Available area per molecule = 1/pNA.m2 (multiply by 1018 to give nm2) Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  solubilization Although an excess of surfactant at the surface, this accounts for a very small proportion The majority of surfactant molecules are in the bulk. Leads to application known as solubilization When adding increasing amounts of surfactant, fall in surface tension very pronounced, then a discontinuity observed over a narrow concentration. After this, fall becomes slight Concentration at which change occurs = critical micelle concentration (cmc) Below cmc = monomers. Dilute solution, apply Gibbs’ equation Above cmc, aggregates called micelles existing in dynamic equilibrium with monomers. Monomer concentration assumed constant Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  CMC Critical ex all. cream droplets Micelle ↳ in water tend to concentration coalesce ↓ use SAM " water solution - form is full/unavailable micelles in continuous => molecules Phase old aggregate together ↓ stirring Isurfactant ↳ micelle PHI cream - - PHO * ollsoluble substances (oe E surface 8 7 tension doesn't change ! u Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Micelle formation ionipulsionregates non-ionic - easier form Attainment of state of minimum free energy Ticelles CC X Structuring of water around hydrophobic group – negative entropy - (energetically unfavourable) If concentration too high, difficult for molecules of surfactant to orientate themselves at packed surface Self-aggregate. Molecules have freedom of movement within micelle since not restrained by water structure Dynamic equilibrium with monomers – continually breaking and reforming Non-ionic surfactants form micelles at lower concentrations (generally 2-3 orders of magnitude) than ionic surfactants (due to repulsion of charged head groups opposing micelle formation) – see in lab Ionic micelles spherical with 70-80% counter ions bound Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  micelles Non-ionic micelles much larger than ionic micelles. Asymmetrically shaped e.g. C16H33(OCH2CH2)21OH (cetomacrogol 1000) thought to be ellipsoidal Also, oxyethylene chains tend to entrap water in addition to water hydrogen bonded – hydrated Factors affecting cmc & micellar size 1. Structure of hydrophobic group Increase in chain length results in decrease in cmc and increase in micellar size 2. Nature of hydrophilic group Increase in hydrophilic portion of molecule will result in increase in cmc Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  Non-ionic surfactants have a lower cmc and higher aggregation number than ionic surfactants with similar hydrocarbon chains. For polyoxyethylated non-ionic surfactants, increasing the polyoxyethylene chain gives a greater hydrophilicity and hence increases cmc Example CH3(CH2)15(OCH2CH2)nOH length pre n=6 n=9 n=21 106 cmc (mol l-1) 1.7 2.1 3.9 Aggregation no. 2430 220 70 (J Chem Soc 907 1963) Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  3. The counter ion More weakly hydrated ion (larger mass) can absorb into the micellar surface and hence decrease charge repulsion between head groups 4. Addition of electrolytes For ionic micelles, addition of electrolytes decreases the micellar size and cmc due to reduction of repulsive forces between surfactant head groups Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  5. Effect of temperature If aqueous solutions of many non-ionic surfactants are heated, become cloudy at cloud point temperature. Solubility of ethoxylate surfactants decreases with increase in temperature (unusual). Reversible. Separation of two phases Conduct experiments below cloud point moreecipitated Note: The Krafft point is the temperature above which the solubility of ionic surfactants increases significantly Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  sites for solubilisation dissolve oil droplets - in the centre of micelle L Water soluble surfactant Medium/long chain polar solubilizate Short chain polar solubilizate Non polar solubilizate C-H. ol droplets Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  · TBL V Plot conductivity versus surfactant concentration – two linear phases, second phase less steep. Change occurs at cmc. Do expt in lab with ionic surfactant (SDS) put more => Nat increase n. of micelles ↓ I - more conductive less steep gradient ~ negative ~ IonI ⑪ read * linear Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations  electrolytes ↓ pull- electrical conductivity of ionic micelles Movement of ions retarded by viscous drag of solvent. On micellization, reduction in drag. One micelle less drag than 100 monomers. This should increase conductance. Ionic atmosphere around micelle exerts breaking affect because unbound counter ions exert attractive force and carry water, so fluid flow counter to movement of micelle. This should decrease conductance. Bound counter ions (70-80%) reduce overall charge on micelle and are moving in opposite direction hence exert retardation force. This may be main factor leading to decrease in conductance. Slide 24 of 24 Surfactants and Their Use in Pharmaceutical Preparations