Suspensions

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  • Created by: LBCW0502
  • Created on: 28-02-18 15:21
What is a suspension?
Coarse dispersion in which insoluble particles (> 1 micron) are dispersed within a liquid medium which is usually aqueous
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What is a pharmaceutical use of a suspension?
Administration of water soluble drugs
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What are suspensions needed for?
All new products (unless problematic), paediatrics, geriatrics, enteral fed patients, insoluble drugs, controlled release
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What are the routes of pharmaceutical suspension delivery?
Oral, intra-nasal, inter-muscular, inter-ocular, topical (suspended solute must not be soluble, Oswald ripening, recrystallisation/crystal growth
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Why are drugs within a solution unstable?
They undergo hydrolysis (in a suspension the drug is isolated for a period of time/low mixing with drug)
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What is Oswald ripening?
Small particles dissolve and deposit on large particles
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Describe features of an ideal suspension
Homogeneous during dosing, easy to re-suspend, proper viscosity, particles should be small and uniform in size
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Is caking a reversible reaction?
No
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Describe features of physical stability
Lyophobic colloids physical stability can be problematic. Suspensions are coarse (contain larger particles). Issue of sedimentation. Must be homogeneous for reproducible dosing
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Sedimentation relates to which law?
Stoke's law
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In terms of physical stability, what does delta p < 0 mean?
Creaming occurs rather than caking
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Does the DVLO theory apply to suspensions?
Yes - Vt = Va + Vr. The secondary minimum is more important (very few coarse suspensions remain suspended)
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What is flocculation?
Forming into an aggregated lumpy of fluffy mass
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What are the three types of flocculation?
Caked/creamed, stable and flocculated
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Describe the process of flocculation
Suspended particles in contact during sedimentation. Large repulsive forces lead to particles passing one another. Closely packed. Lowest layer pressed. Repulsive barrier overcome (caking). Can't be re-dispersed
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Which forces are stronger in flocculation?
Attractive forces (course compact mass). Weakly attracted clusters form (smaller attractive forces). Re-disperse upon shaking
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Describe features of flocculated systems
Particles are aggregated, fast sedimentation, fluffy sediment, large sedimentation volume
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Describe features of deflocculated systems
Particles remain as discrete units, slower sedimentation, compact sediment, small sedimentation volume
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How do you calculate the sedimentation volume ratio?
F = Vu / Vo (final settled volume/original volume, gives degree of flocculation)
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Describe features of under flocculation
Compact sediment, difficult to re-suspend
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Describe features of over flocculation
Might be irreversible, high viscosity, unattractive product, fast sedimentation
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What causes deflocculation?
Addition of surfactants
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How is controlled flocculation achieved?
Particle size, use electrolytes (control repulsion), adding flocculating agents - Schulze-Hardy Rule
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What is the Schulze-Hardy rule?
Increase in valency of counter ion leads to increase in concentration required to cause aggregation
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How do electrolytes affect controlled flocculation (DVLO)?
Low conc/large diffuse region (large primary maximum/secondary minimum). Intermediate conc/compression of diffuse layer (smaller primary max/appearance of secondary minimum). Large conc/complete compression of diffuse layer (no primary max/unstable)
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What is the effect of flocculating agents on controlled flocculation?
Surfactants (ionic-zeta potential/non-ionic bridging), polymers (bridging/increase viscosity) - stabilisation
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Describe features of steric repulsion
Adsorbed macromolecules, positive enthalpy change (interact), negative enthalpy change (conformation), osmotic effect (dilution)
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Describe features of wetting agents
Dispersion of hydrophobic solid in aqueous environment. Wettability of powder (contact angle). Large contact angle (poor wetting). Reduce surface energy. Surfactants. Prevent absorption to packing
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What is included in a suspension formulation?
Solvent, drug, surfactant, wetting agent, taste, viscosity and preservative
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What are the requirements for the solvent?
Must be biocompatible, not highly volatile, must not facilitate in particle dissolution (options - purified water, glycerol, alcohol, glycols)
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What are the requirements for suspending and wetting agents?
One additive can achieve both. Control flocculation (buffer). Surfactants (e.g. Span, Tween), lyophilic colloids, dispersed/dissolved in solvent, adsorb to drug, increase wetting < aggregation < adsorption to packing
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Give examples of sweetening agents
LMW carbohydrates (sucrose), polyhydric alcohols (sorbitol), artificial sweeteners e.g. sodium saccharin
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Give examples of flavours
Aromatic oils e.g. peppermint, fruit juices e.g. apricot, herbs and spices e.g. anise
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What are the requirements for viscosity modifying agents?
Polysaccharides (acacia/lyophilic, tragacanth/lyophilic/thixotropic, alginates/lyophilic), water soluble celluloses (methylcellulose), hydrates silicates (bentonite), carbomers (synthetic polymer), colloidal silicon (aerosil)
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What are the requirements for the preservative?
Minimal absorption, ensure efficacy at suspension pH (e.g. benzoic acid, esters, parabens)
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Give examples of other additives
Buffers, antioxidants, colours
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Give an example of a simple suspension
Paracetamol, sucrose, glycerol, sorbitol, methyl hydroxybenzoate, xanthan gum, purified water
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Which chemical factors are considered in formulation stability?
Analysis (e.g drug, excipients, preservative)
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Which physical factors are considered in formulation stability?
Measure and manipulation
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Describe features of the zeta potential
Approximation of surface charge, used to control physical stability, very high/low zeta leads to poor stability (good value - 60 mV). Measure
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What is the consequence of having particles greater than 10 microns?
Aggregation
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What is the consequence of having particles with a size of 10 microns?
Physically stable
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What is the consequence of having particles smaller than 10 microns?
Dissolving
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How is particle size measured?
Microscopy, sedimentation, electrical sensing zone method (coulter counter), light scattering (colloids), laser diffraction - frequency distribution curves
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Describe features of particle size in microscopy
Laborious, shape, best for solids, particle is visualised, shape can be accounted for, discrimination possible
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Describe features of sedimentation
>10 microns gravitational, >0.5 microns centrifugal. Anderson pipette (formulae). Laborious, shape, inaccurate at low particle sizes, particle not visualised, user dependent, no discrimination
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Describe features of electrical sensing zone method for particle size
Number, simple, mixed samples, good size range, solvents limited, user-friendly
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Can laser scattering be used for suspensions?
No - light scattering is used for colloids due to particle size
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Describe features of laser diffraction for particle size
Beam expander, measuring zone, sample in, sample out, lens, detector (most common method)
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What are the advantages of laser diffraction particle size analysis?
Very quick, measure particles in wide variety of environment, data manipulation is quick and easy, little user dependence, equipment cheap and available
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What are the disadvantages of laser diffraction particle size analysis?
Not accepted by FDA/MCA. Requires computational input. Absolute accuracy in formulations. Concentration dependent
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What would be the most appropriate method to measure the physical stability of a paracetamol suspension containing 50 mg/mL of drug?
Laser diffraction
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What is a pharmaceutical use of a suspension?

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Administration of water soluble drugs

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Card 4

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What are the routes of pharmaceutical suspension delivery?

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Card 5

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Why are drugs within a solution unstable?

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