Colloid An Introduction Physical Pharmacy 2 4/25/2017 Colloid An Introduction Kausar Ahmad Kulliyyah of Pharmacy http://staff.iium.edu.my/akausar Physical Pharmacy 2 KBA

Lecture 1: Lecture 2: Contents Types of colloids Types of dispersions Physical Pharmacy 2 4/25/2017 Contents Lecture 1: Types of colloids Types of dispersions Lecture 2: Types of emulsions Emulsification factors Physical Pharmacy 2 KBA

Colloidal System Particle size below 1 mm High specific surface area Physical Pharmacy 2 4/25/2017 Colloidal System Particle size below 1 mm High specific surface area Discrete particles dispersed in a different medium In pharmaceutical emulsions or suspensions, particle size ranges from colloidal to visible or coarse. Physical Pharmacy 2 KBA

Multiple emulsion: w/o/w, o/w/o Physical Pharmacy 2 4/25/2017 Types of Colloids Type Dispersed phase Continuous phase Emulsion: o/w oil water Emulsion: w/o Suspension solid water or oil Aerosol solid or liquid air Others Multiple emulsion: w/o/w, o/w/o Physical Pharmacy 2 KBA

Classification Based on Size Physical Pharmacy 2 4/25/2017 Classification Based on Size Class Size Examples Molecular dispersion < 1.0 nm glucose Colloidal dispersion 1.0 nm - 0.5 mm Natural rubber latex Coarse dispersion > 0.5 mm red blood cells Physical Pharmacy 2 KBA

Classification of dispersed systems Physical Pharmacy 2 4/25/2017 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 Sol – refers to any colloidal system in which the dispersion medium is a liquid. Lyophilic sol – a sol consisting of a dispersed phase which has an affinity for the continuous phase. This means that the colloid is readily formed e.g. starch in water. Lyophobic sol – a sol which is solvent-repelling, such that the disperse phase has little or no attraction for the dispersion medium e.g. gold in water. Physical Pharmacy 2 KBA

Colloidal Phenomena milk detergency coconut milk ice-cream Physical Pharmacy 2 4/25/2017 Colloidal Phenomena detergency milk coconut milk ice-cream Detergency Most important products using surfactants Main component is surfactant Involves in adsorption, wetting, emulsification and dispersion Wetting of substrate ->soil-removing process ->preventing soil redeposition (PEG) Physical Pharmacy 2 KBA

Pharmaceutical suspensions Physical Pharmacy 2 4/25/2017 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 KBA

Preparing a Dispersion Physical Pharmacy 2 4/25/2017 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 Modifying the viscosity to minimise sedimentation Dry powders usually consist of aggregates and agglomerates which need to be dispersed in the liquid to produce "individual" units which may be further subdivided into smaller particles. This requires understanding of various phenomena such as powder wetting, dispersion of aggregates and agglomerates and comminution of the primary particles into smaller units. HOW? Once a powder is dispersed into a liquid, it is essential to prevent aggregation of the particles and their sedimentation. Powder wetting, dispersion and subsequent stabilization requires in most cases the use of a dispersing agent, usually a surfactant, a polymer or polyelectrolyte. Physical Pharmacy 2 KBA

Properties of dispersing agents Physical Pharmacy 2 4/25/2017 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 KBA

Pharmaceutical Emulsions Physical Pharmacy 2 4/25/2017 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 KBA

Emulsification emulsifier homogeniser OIL WATER Physical Pharmacy 2 4/25/2017 Emulsification emulsifier homogeniser OIL WATER Physical Pharmacy 2 KBA

Emulsification Factors Physical Pharmacy 2 4/25/2017 Emulsification Factors Concentration of dispersed/oil phase Types & concentrations of surfactants Emulsifying temperature especially for non-ionic surfactants Type of homogeniser Physical Pharmacy 2 KBA

Types of Emulsions Macroemulsion Nanoemulsion Microemulsion Physical Pharmacy 2 4/25/2017 Types of Emulsions Macroemulsion Nanoemulsion Microemulsion Multiple emulsion Physical Pharmacy 2 KBA

Nanoemulsion and Microemulsion Physical Pharmacy 2 4/25/2017 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 KBA

Methods of Preparation Physical Pharmacy 2 4/25/2017 Methods of Preparation Nanoemulsions are easily formulated using high-pressure 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 KBA

Multiple Emulsion Dispersed phase contains droplets of another phase. Physical Pharmacy 2 4/25/2017 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 KBA

Example of w/o/w emulsion for drug delivery by intra-muscular route Physical Pharmacy 2 4/25/2017 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 KBA

Multiple Emulsion for Pharmaceuticals Examples Physical Pharmacy 2 4/25/2017 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). 11/6/2003 J Wang et al, Journal of Controlled Release 82 (2002) 289-307 Physical Pharmacy 2 KBA

Multiple emulsion Pharmaceutical Problems Physical Pharmacy 2 4/25/2017 Multiple emulsion Pharmaceutical Problems 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. Rapid release during the first day 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. Very slow release period after the initial burst period. Physical Pharmacy 2 KBA

Physical Pharmacy 2 4/25/2017 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 KBA