MPharm Programme Colloids & Suspensions PDF

WEEK MPharm Programme Colloids & Suspensions Dr Paul Carter Slide 1 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK What are colloidal particles? large molecules...

WEEK MPharm Programme Colloids & Suspensions Dr Paul Carter Slide 1 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK What are colloidal particles? large molecules or finely divided small particles dispersed in a medium. Lie between a true solution and a coarse suspension. Seen with electron microscope and will not pass through semi- permeable membrane. Size 10-9 m to 10-6 m have at least one dimension between 1nm to 1 µm all 3 dimensions not necessarily in colloidal range e.g. fibres. sometimes difficult to make distinction between colloidal and non- colloidal examples of colloidal systems: aerosols, cosmetics, paint, cement, rubber and pharmaceuticals - use colloidal systems for drug delivery and nanoparticle technology. Slide 2 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Classification of colloidal particles Lyophobic colloids solvent hating e.g. water insoluble drugs, clays, oily phases, suspensions of microorganisms, blood, metals be careful, because some water insoluble drugs are hydrophilic e.g. kaolin. Classed as lyophobic but not 'water hating‘ lyophobic dispersions not formed by spontaneous dispersion in the medium thermodynamically unstable and will separate (but some may remain suspended for a long time) because of size, high surface area – a reduction in surface area (e.g. droplets coalescing or particles aggregating) reduces their free energy – favourable Note: 'disperse phase' - phase that is subdivided and dispersed in the 'continuous phase' Slide 3 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Classification of colloidal particles Lyophilic colloids ‘solvent loving’ e.g. surfactants, proteins, gums. solutions (colloidal, not ‘true’ solutions) formed spontaneously and hence thermodynamically stable if water the solvent - termed hydrophilic Examples of colloidal systems: Foam liquid in gas Milk liquid/liquid emulsion Smoke solid in gas polydisperse aerosol Slide 4 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Properties of colloids Kinetic properties (motion of particles) Interactions lead to aggregation (or coalescence for liquid droplets) and hence the colloidal system destroys itself Brownian motion In dispersion of fine particles in a liquid (or gas), interactions between particles occur as a result of Brownian motion random collisions with molecules of dispersion medium (particles travel in zig-zag fashion) Slide 5 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Properties of colloids - kinetic Sedimentation (solid particles) and Creaming (emulsions) Stokes' law Spherical particles of radius (r) and density (σ) falling in a liquid of density (ρ) and dynamic viscosity (η), the velocity of sedimentation (or creaming) (v) is determined by: V = 2 r2 g (σ-ρ) 9η Reduce V by: Forming smaller particles Increasing the viscosity of the continuous phase Decreasing the density difference between the two phases Slide 6 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Question example A particle which has a mean diameter of 1.5 µm, and true density of 3580 kg m-3 is suspended in an aqueous solution of density 1080 kg m-3 and viscosity 1.12 g m-1 s-1 note, units for dynamic viscosity are Pa.s = N. m-2.s = kg.m.s-2.m-2.s = kg.m-1.s-1). calculate the velocity of sedimentation (m s-1) under gravity (g=9.81 m. s-2) What distance would the particle fall in 1 hr? Slide 8 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Question example V = 2 r2 g (σ-ρ) 9η therefore V = 2. (0.75 x 10-6)2.(9.81).(3580-1080) 9.(1.12 x 10-3) V = 2.74 x 10-6 m s-1. In 1 hr, particle would fall 2.74 x 10-6 x 3600 = 9.86 x 10-3 m. Slide 9 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Properties of colloids - kinetic Diffusion colloidal particles spontaneously diffuse from a region of higher concentration to lower concentration. rate described by Fick's first law: dm/dt = -DA dC/dx dm is mass of substance diffusing in time dt across area A under conc gradient dC/dx. D is diffusion co-efficient (cm2 s-1). Minus sign shows diffusion in direction of decreasing conc. Other properties such as osmotic & optical – beyond the scope of this lecture Slide 10 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Pharmaceutical suspensions Dispersion of insoluble drug in aqueous/non-aqueous continuous phase may be colloidal ( e.g. magnesium hydroxide often in colloidal range) or often a bit coarser (therefore gravity will have large impact) Why have suspensions? Difficulty in swallowing solid dosage formulations Stability of drugs e.g. hydrolysis of drugs in solution Taste High surface area Main problems: Sedimentation Caking Flocculation Particle growth (dissolution and recrystallisation) Slide 14 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Types of suspension Classified according to: Dispersion medium: aqueous or oily Formulation: flocculated or defloccuated Stability of the drug: – Ready to use Suspensions (stable drugs) – Reconstituted powder (non stable drugs) Uses: – Oral, – Parenteral – Topical preparations – Ocular eye drops (hydrocortisone and neomycin) – X- ray contrast media Slide 15 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Formulation of suspensions in practice, avoid aggregation/caking and adhesion of particles to vessel surfaces produce a flocculated system a floc is a loose assembly of particles ideal suspension is partially (not fully) flocculated A fully flocculated system: clear supernatant large sediment volume rapid sedimentation easily redispersed Slide 16 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Flocculated suspension Clear supernatant (no individual particles left) Large sediment volume – bulky flocs (loose aggregates of particles) Loose clusters easily redispersed on shaking Reform and sediment rapidly (Stokes’ law) Slide 17 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Deflocculated suspension Fully deflocculated: Cloudy supernatant (individual particles present) Small sediment volume (cake formation) Slow sedimentation (small particles – gravity acts and pushes particles to bottom but some too small and remain suspended) Difficult to redisperse (strong van der Waals forces between closely packed particles) Because of cake formation – deflocculated systems are no good for pharmaceutical suspensions Slide 18 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Partial flocculation Deflocculated systems: have the advantages of slow sedimentation rate thus enabling a uniform dose to be taken from the container, but when settling does occur, the sediment is compact and difficult to redisperse. Flocculated systems: form loose sediments which are easily redispersed but the sedimentation rate is fast and there is a danger of an inaccurate dosage and the product would look inelegant. A compromise is reached in which suspension is partially flocculated and viscosity is controlled so that the sedimentation rate is at a minimum. Slide 19 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Formulation of suspensions Main stages: size reduction (coarse suspension > 1µm) Large particles, if greater than about 5 μm diameter, will: – impart gritty texture to the product and settle quickly – cause irritation if injected or instilled into the eyes – block hypodermic needle (over 25 μm) diameter particularly if acicular in shape rather than isodiametric Use a particular particle size range to control the rate of release of drug and the bioavailability It is advantageous to use a suspended drug of narrow size range – Polydispersed drug particle size may give very small crystals ( divalent > monovalent Electric potential Ψ mV Electric potential Ψ mV 10-3 M Monovalent 10-2 M Bivalent 10-1 M Trivalent Distance Distance Slide 33 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Thickening agents Used to modify the viscosity of the vehicle Examples include – Acacia – Starch – Hydroxyethylcellulose – Carmellose sodium Slide 37 of 38 MPharm Routes of Administration- Colloids & Suspensions WEEK Quality control physical appearance particle size analysis ease of redispersal F (sedimentation volume ratio) = V/Vo where V = final settled volume of sediment and Vo = total volume of suspension. zeta potential rheology – particles should remain suspended during storage. Higher shear rate conditions such as shaking and pouring require particles to be mobile. shear rate thinning or thixotropy (time dependant reversible loss of structure) are desirable qualities Slide 38 of 38 MPharm Routes of Administration- Colloids & Suspensions