PS 7 G

• excipients in suspensions


  solvents: purified/ultrapure water with mixtures of ethanol and glycerol. buffers: lactose. isotonicity modifiers (non-oral): NaCl, glucose. viscosity modifiers, suspending agents, thickeners: glycerol, syrup, alginate. flocculation modifiers: NaCl, surfactants, hydrophilic polymers. Antimicrobial preservatives: benzoic acids, parabens. antioxidants: ascorbic acid. sweeteners: sugars. flavouring and colourants.
• manufacture of suspenions


  step-wise addition of soluble ingredients to solvents (heating and agitation to facilitate dissolution), filtration, cooling, addition of finely divided active ingredients (dry substance or aqueous vehicle), blending, QC testing (appearance, pH, viscosity, potency, particle size, distribution, suspendability of actives, preservative conc and efficiency). packaging and labelling
• packing suspension


  bottles: glass, plastic, opaque. CRC. ampoules and vials: glass and plastic with polymeric stoppers. some suspension products with poorly stable actives are prepared and packaged as dry powders (oral) or freeze-dried powders (for injection) to be reconstituted immediately before use
• advantages of oral suspension


  drug dispersed and ready to dissolve, solid is more stable than liquid, allows for relatively high concentration and therefore smaller dose volume. easy to homogenise. drug in solid state may be more palatable. easy to make palatable by adding flavourings and sweeteners. easy to measure the required dose (with care). easy dose adjustment, administration and swallowing. good for paediatrics and geriatrics with swallowing difficulties.
• disadvantages of oral suspensions


  drug must dissolve before it can be absorbed. susceptible to microbial contamination. short shelf life compared to dry solid forms. bulky and less convenient to store/transport. glass container breakage. difficulty disguising drug taste sometimes. disagreeable texture. dose measurement susceptible to error. suspension inherently unstable (gravity), solids may settle separately and form a hard close-packed "cake", flocculation, crystals dissolve and regrow on larger particles (increased SA) reducing suspendability, must be shaken which may cause frothing
• density

  mass per unit volume (p) . g/mL or g/cm^3.
• specific gravity

  the weight of a certain volume of a substance divided by the weight of an equal volume of water. SG units/unitless. water has density of 1 g/mL at 25 degrees
• viscosity / dynamic viscosity


  the measure of resistance to flow, the amount of force required to make something flow (n). the more viscous the less likely to dissolve. normally declines as temp increases. units: pascal second Pa.s or poise P, 1 Pa.s is 1000mPa.s or 10 poise. 1mPa.s is 1 centipose cP or 100 poise. kinematic viscosity: n/p (dynamic viscosity/density)
• measuring viscocity

  ostwald viscometer. u-shaped tube. liquid is place inside the tube on 1 side, and it is sucked up until it reaches a mark on the other side, the it is released and let flow to a mark. this is timed and then measured in pa.s. falling sphere viscocometer: a tube with a ball in sample fluid, how long it takes for the ball to move from one mark to another. rotational viscometer, apparent viscosity is calculated from the magnitude of the torque caused bu the drag on a roataing cylinder in a liquid. low viscosity is quicker.
• temp on viscosity


  as temp increased viscosity decreases. true for water, ethanol and solutions
• sedimentation

  a suspended insoluble substance that is denser than the solvent will inevitably sediment due to gravity. 3 forces that affect this: buoyancy, less dense substances are pushed up (upthrust). gravity (mass x gravitational constant). drag tending to slow particle descent, depends on particle size and viscosity.
• stokes law of sedimentation velocity

  theoretical, only applies if particles are spheres, conc of particles must be low so particles move freely and do not interfere with each other, particle size must be 0.1 to 100 microns of 0.0001mm to 0.1 mm (too small disturbed by Brownian motion of fluid molecules, too large creates turbulence). according to the formula to reduce the velocity of sedimentation: reduce the diameter of particles, increase the density of the fluid, increase the viscosity of fluid
• Brownian motion


  everything is moving and vibrating, random particles will collide and be disturbed because they are so small
• zeta potential

  suspended paticles can have electric charges (polarity) and result in repulsion and attraction, attraction can form bigger particles affecting the sedimentation rate.
• flocculation


  zeta potentials cause particles to repel each other and remain separate however if the other forces of attraction between suspended particles exceed the electrical forces of repulsion, the particles form loose aggregates that behave as if they are relatively large particles and precipitate quickly
• deflocculated vs flocculated sediments


  deflocculated: forms slowly, compact and caked, the supernatant liquid is cloudy and difficult to resuspend. flocculated sedminet forms quickly and is loose and fluffy, the supernatant liquid is clear, and the solids can be resuspended by shaking.
• colloidal systems


  solute is distributed in microscopic irregular clumps (colloids) less then 0.5 um. produced by milling or ultrasonication under special conditions. colloids are kept in suspension and constant motion by their Brownian movement and solvent movement. too small to be seen by naked eye, but diffuse light from a beam. Detecting used ultramicroscopy or transmission electron microscopy. colloids absorb ions, become charged and repel each other. opposite charge colloids are added, colloids coagulate and precipitate out. silver colloid (germicide)
• types of pharmaceutical suspenions


  oral, topical lotions, eye drops, ear drops, nasal drops and sprays, subcutaneous and. intramuscular injections, rectal enemas, metered drug inhalers.
• formulation of suspensions


  a pharmaceutical suspension is a two-phase disperse system where a solid phase (typically active ingredient as 1-100 um sized particles) is distributed throughout suspended in a liquid phase