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Colloid An Introduction Kausar Ahmad Kulliyyah of Pharmacy http://staff.iiu.edu.my/akausar Physical Pharmacy 2 1 Contents Lecture 1: • Types of colloids • Types of dispersions Lecture 2: • Types of emulsions • Emulsification factors Physical Pharmacy 2 2 Colloidal System Particle size below 1 mm High specific surface area Discrete particles dispersed in a different medium Physical Pharmacy 2 3 Types of Colloids Dispersed phase Continuous phase Emulsion: o/w oil water Emulsion: w/o water oil Suspension solid water or oil Aerosol solid or liquid air Others Multiple emulsion: w/o/w, o/w/o Type Physical Pharmacy 2 4 Classification Based on Size Class Molecular dispersion Colloidal dispersion Coarse dispersion Size < 1.0 nm Examples glucose 1.0 nm - 0.5 mm Natural rubber latex > 0.5 mm Physical Pharmacy 2 red blood cells 5 Classification of dispersed systems hydrophilic colloidal dispersion (in water) • surfactant micelles and phospholipid vesicles, also known as association colloids lyophilic colloids • proteins, gelatin • rubber, gum lyophobic/hydrophobic colloids • gold, silver and sulfur • emulsion Physical Pharmacy 2 6 Colloidal Phenomena detergency milk coconut milk ice-cream Physical Pharmacy 2 7 Pharmaceutical suspensions Coarse dispersions • Solid-in-liquid Main function • Delivery vehicle for suspended drug particles Surfactant/dispersant reduces interfacial energy • Stabilisation by electric repulsive force & steric hindrance effect Examples: Oral suspensions, topical applications, injectables Physical Pharmacy 2 8 Preparing a Dispersion Particle size reduction surface of each primary particle is available to liquid. Wetting of powder wet external surfaces & displace air between internal clusters. Dispersing by using charged bulky surfactants Provide strong interfacial layer Physical Pharmacy 2 Modifying the viscosity to minimise sedimentation 9 Properties of dispersing agents adsorption of surfactants at the solid/liquid interface. highly charged provide steric hindrance END OF LECTURE 1 OF 2 Physical Pharmacy 2 10 Pharmaceutical Emulsions Emulsion • liquid-in-liquid vehicle • o/w or w/o Main function • provide vehicles for drug delivery and parenteral nutrition. • drug is dissolved in the water or oil phase. Surfactant/emulsifier reduces interfacial energy • emulsion becomes thermodynamically stable Examples: • parenterals, creams, lotions Physical Pharmacy 2 11 Emulsification emulsifier homogeniser OIL WATER Physical Pharmacy 2 12 Emulsification Factors Concentration of dispersed/oil phase Types & concentrations of surfactants Emulsifying temperature especially for nonionic surfactants Type of homogeniser Physical Pharmacy 2 13 Types of Emulsions Macroemulsion Nanoemulsion Microemulsion Multiple emulsion Physical Pharmacy 2 14 Nanoemulsion and Microemulsion Nanoemulsions: 50-200 nm Microemulsions: 5-50 nm long term physical stability against creaming, flocculation and coalescence Due to small size they enhance penetration, spreading and will give uniform distribution on the substrate on which they are applied. Examples: personal care products and cosmetics, agrochemicals, pharmaceuticals, household products etc. Physical Pharmacy 2 15 Methods of Preparation Nanoemulsions are easily formulated using highpressure homogenizers with proper choice of surfactants and/or polymers. The production of microemulsions may employ the Phase Inversion Temperature (PIT) principle. These emulsions are stabilised through steric stabilization and by the thickness of the adsorbed layer. Physical Pharmacy 2 16 Multiple Emulsion Dispersed phase contains droplets of another phase. o/w/o or w/o/w. Prepared through a double homogenization process or a one step procedure using the PIT. Both are important for drug delivery. Physical Pharmacy 2 17 Example of w/o/w emulsion for drug delivery by intra-muscular route Advantage of w/o: slow-release because drug has to diffuse through oil disadvantage: viscosity of medium (oil) is high solution: to disperse the w/o in aqueous medium. • On injection, the aqueous phase dissipates rapidly leaving behind the w/o. Physical Pharmacy 2 18 Multiple Emulsion for Pharmaceuticals Examples Sandostatin LARTM Depot Novartis (hypothalamic hormones analogue) Control of hypersecretion at the site of the tumour where hormone overproduction starts Human NutropinTM Depot Alkermes/Genentech (human insulin suspension) somatropin (rDNA origin) for injectable suspension long-acting dosage form of recombinant human growth hormone (rhGH). Physical Pharmacy 2 19 Multiple emulsion Pharmaceutical Problems Rapid release during the first day • typically accounts for 10-80% of the total drug loading. • This ‘initial burst’ poses a toxicity threat & is a major hurdle for the development of microspheres. Very slow release period after the initial burst period. • This can last for weeks and is referred to as the ’lag-time’. • During this induction period, the patient is not effectively treated due to lack of drug release. Physical Pharmacy 2 20 References PC Hiemenz & Raj Rajagopalan, Principles of Colloid and Surface Chemistry, Marcel Dekker, New York (1997) HA Lieberman, MM Rieger & GS Banker, Pharmaceutical Dosage Forms: Disperse Systems Volume 1, Marcel Dekker, New York (1996) F Nielloud & G Marti-Mestres, Pharmaceutical Emulsions and Suspensions, Marcel Dekker, New York (2000) J Kreuter (ed.), Colloidal Drug Delivery Systems, Marcel Dekker, New York (1994) Physical Pharmacy 2 21