Disperse Systems Flashcards
what is a disperse system?
liquid preparation containing undissolved or immiscible drug dispersed through a vehicle
which is the dispersed phase and which is the dispersing phase?
dispersed = distributed substance dispersing = vehicle
what is the difference between a suspension and an emulsion?
suspension: dispersed phase is a solid
emulsion: dispersed phase is a liquid
what is the term for the disperse system when air is the vehicle?
aerosol
what is the difference between a coarse dispersion and a fine/colloidal dispersion?
coarse: particle size is 10-50um
fine/colloidal: particle size 0.5-10um
give an example of a coarse dispersion and a fine/colloidal dispersion
coarse: suspensions, emulsions
fine: magmas, gels
what does particle size have to do with separation from vehicle?
the larger the particle size, the greater the tendency to separate from the dispersing medium
what is one important thing to do before using a disperse system?
shake well before use to distribute drug evenly
what is a suspension?
two phase system consisting of a finely divided solid dispersed in a (usually aqueous) liquid phase
what is the general oral use for suspensions? topical use?
oral: sweetened flavour formulations
topical: lotions
what are 4 advantages to suspensions?
1) useful for pts who have difficulty swallowing tablets/capsules but the drug is insoluble
2) flexibility in giving doses
3) mask unpleasant taste
4) more stable than solutions
what are 2 disadvantages to suspensions?
1) unstable (solids will settle over time leading to lack of uniformity)
2) possible unpleasant mouth-feel/texture (large particle size)
what are 3 desirable attributes of a suspension?
1) suspension should settle slowly and be readily re-dispersed with gentle shaking
2) particle size should remain fairly constant over shelf life of the product
3) suspension should pour readily and evenly from its container
what is Stokes’ law?
dx/dt = (d^2(pi-pe)g)/18n dx/dt = rate of settling d = particle diameter pi = particle density pe = medium density g = gravitational constant n = medium viscosity
what does Stokes’ law indicate about rate of settling
rate of settling is a function of particle size (smaller particles settle slower) and inverse function of viscosity (more viscous solutions settle slower)
what could happen if particle size is too small?
caking may occur, and drug will not re-disperse
how do you prevent caking from occurring?
form a floccule
what is a floccule?
loose aggregation of the particles held together by van der Waals forces, allowing for easy re-dispersion
How do you form a floccule?
Add a small amount of surfactant or electrolytes to neutralize the particle surface charges
Floccules usually settle faster, how do you prevent this?
add suspending agent to increase viscosity
what are 2 suspending agents?
methylcellulose polyvinylpyrrolidone (PVP)
what are 2 characteristics of a desirable suspension?
pseudoplastic
thixotropic
what is considered low shear rate? high shear rate?
low: storage, just after shaking, while pouring
high: shaking
what does thixotropic mean?
slow recovery from deformation (shaking), remaining in fluid long enough to be poured
what does pseudoplastic mean?
higher viscosity at lower shear rates and lower viscosity at higher shear rates
what is extemporaneous compounding?
the preparation of a prescription drug in a pharmacy according to the given prescription
what are two properties to keep in mind with extemporaneous compounding?
stability
bioavailability
what is the first step for extemporaneous compounding?
empty appropriate # of capsules/grind up tablets and add a small amount of vehicle/levigating agent to make smooth paste
what is the second step for extemporaneous compounding?
add vehicle with continuous mixing then add to graduated cylinder and bring to volume
what preservatives should be avoided with infants and neonates? what does this mean in terms of expiry date?
alcohol
propylene glycol
expiry: short beyond use date (14 days) and require refrigeration
what is the expiry date for products containing preservatives?
25% of remaining expiration date of commercial product or 6mo. whichever comes first
What is the process used for dry powders for oral suspensions?
must first loosen the powder then add the correct amount of solvent (usually water) accurately measured
what is an emulsion?
a dispersion in which the dispersed phase (internal phase) is composed of small droplets of liquid distributed throughout a vehicle, in which it is immiscible
What is the difference between oil in water (o/w) and water in oil (w/o) emulsions?
o/w: continuous phase is aqueous
w/o: continuous phase is oleaginous
what dose forms could emulsions be used for?
oral
topical (most)
parenteral
ophthalmic
why aren’t emulsions used for oral use very often?
poor patient acceptance (oily and unpalatable)
when is it better to use a w/o topical emulsion? why?
on unbroken skin since it’s easier to apply as a thin film, softening on the skin (resists drying) and tends to be more occlusive/more difficult to remove.
what is good about o/w topical emulsion?
less greasy feel
easier to remove with washing
small particle size of internal phase may promote better absorption of medication
what is creaming?
occurs when the dispersed internal phase droplets merge and rise to the top (o/w) or settle to the bottom (w/o) but can be re-dispersed by shaking
what is breaking or cracking?
occurs when the internal phase undergoes coalescence and there is complete and irreversible separation of the dispersed phase
what is one way to stabilize emulsions?
use of emulsifying agents
what are some examples of emulsifying agents?
surfactants
hydrocolloids
solid particles
whats an example of a cationic surfactant? anionic surfactant? non-ionic surfactant?
cationic: benzalkonium chloride
anionic: sodium docusate, sodium oleate
non-ionic: spans and tweens
why are cationic surfactants rarely used?
irritating and potentially toxic in amounts required
what are examples of natural hydrocolloids? semi-synthetic? synthetic?
natural: acacia, gelatin
semi: methylcellulose
syn: carbopols
how do solid particles work as an emulsifying agent?
form a layer around the dispersed droplets and tend to swell in the dispersion medium to increase viscosity and reduce the attraction between the dispersed droplets
what are some examples of solid particle emulsifying agents?
bentonite
aluminum hydroxide
magnesium trisilicate
what are some examples of auxiliary emulsifying agents?
fatty acids (stearic acid) fatty alcohols (cetyl alcohol) fatty esters (glyceryl monostearate)
what is the function of the hydrophilic-lipophilic balance (HLB)?
aid in making decisions about the amount and types of emulsifying agents needed to form stable products
how does the HLB work?
arbitrary scale of 1-18 assigned to emulsifying agents
low HLB: lower number of hydrophilic functional groups on the molecule (oil soluble) therefore oil phase will predominate (w/o)
high HLB: indicates water solubility, water phase will predominate (o/w)
what is the HLB equation?
HLB = ((qty surfactant 1)(HLB surfactant 1) + (Qty surfactant 2)(HLB surfactant 2))/(qty surfactant 1 + qty surfactant 2)
what are the 4 methods of emulsion preparation in a pharmacy?
1) continental method
2) english method
3) bottle method
4) beaker method
what is usually in a primary emulsion for the continental method?
oil (4 parts)
water (2 parts)
hydrocolloid/gum-type emulsifier (1 part) - usually acacia
how do you prepare the primary emulsion?
levigate the gum with 4 parts of oil until powder is thoroughly wetted, then 2 parts water added at once
mixture vigorously triturated until its creamy white and is viscous
when are water soluble ingredients added to the primary emulsion? oil soluble?
water - after primary emulsion is prepared
oil - added to oil prior to making primary emulsion
what occurs after the primary emulsion is made in the continental method?
transfer to a measuring cylinder and make to volume and shake to ensure uniform distribution
what is the english method of preparing a primary emulsion?
use the same ratio, but the gum is triturated with the water and then the 4 parts oil is added in portions with vigorous trituration
when can you use the bottle method?
when using oils of low viscosity
how is an emulsion prepared using the bottle method?
same ratio, but gum is added to the bottle then oil is added and shaken
water is added next and shaken to mix
in what case would you not use the 4:2:1 ratio for making emulsions? why? what method is this for?
when synthetic emulsifiers are used because a smaller amount of emulsifying agent is required
beaker method
how does the beaker method work to prepare an emulsion?
oil soluble components are dissolved in the oil; water soluble components are dissolved in water.
both solutions heated to 70C in a water bath and then internal phase is added to the external phase with stirring until product reaches room temperature
What is a colloidal dispersion?
those where the particle size ranges from 1nm to 1um
could be single large molecules of high MW or aggregates of smaller molecules
how can you tell a colloidal dispersion from a true solution?
opaque particles scatter light when a beam of light is passed through at right angles (Tyndall effect)
true solution = no scattering
how is uniform dispersion maintained in colloidal dispersions?
brownian movement (due to particles being bombarded by molecules of dispersing medium)
what are the two types of colloids in regards to interaction with the solvent?
lyophilic - solvent loving
lyophobic - solvent hating
what are hydrophilic molecules?
have an affinity for water and when dispersed in water, they become hydrated
what happens with a hydrophilic molecule becomes hydrated?
they swell and increase the viscosity of the system
what happens when the viscosity of a system is increased? why?
improvement in stability
reducing interaction between particles so there is less tendency for particles to coalesce, increase in size, and settle
what charge do gums like acacia and methylcellulose possess? why?
negative
carboxylic and sulfate functional groups
how can surface charge influence a colloidal dispersion?
presence of surface charge produces repulsion of particles and reduces the chance that the particles will adhere and settle (increase stability)
what type of colloidal dispersions are usually made?
hydrophilic
what happens when surfactant molecules are introduced in water?
form micelles
which is more of a concern regarding stability: hydrophilic or hydrophobic colloids? why?
hydrophobic
no affinity between dispersed and continuous phases, meaning no change in viscosity occurs
what are some examples of hydrophobic colloids? (5pts)
oils water-insoluble drugs silver chloride gold sulfur
how can you increase the stability for a hydrophobic colloid?
create some affinity between the particles and the continuous phase by using surfactants or protective colloids
what may cause a hydrophobic molecules to carry an electric charge?
absorption of electrolyte ions from solution
how can you neutralize the particle? what happens when you neutralize the particle?
addition of ions of opposite charge
neutralized particles will coalesce and precipitate
what influence neutralization efficiency?
valence of the ion
rank the following ions from most effective to least effective at neutralizing a negative charge?
Aluminum
Calcium
sodium
aluminum > Ca > Na
what is the use of gelatin (hydrophilic colloid)?
add it to a hydrophobic colloid, and the gelatin is adsorbs onto the hydrophobic colloid and surround it, making it behave like a hydrophilic colloid (protects from electrolytes)
what are some examples of colloidal systems in pharmacies?
vitamin K1
cyclosporine A
paclataxol
amphotericin-B injections
what are gels? (2def’ns)
hydrophilic colloidal systems
semisolid systems consisting of suspensions made up of small inorganic particles/large organic molecules interpenetrated by a liquid
how are gels made?
using agents which undergo a high degree of cross-linking or association when hydrated, increasing viscosity of the system
what restricts movement of the dispersing phase?
interlacing 3D network of particles or solvating macromolecules
what is the typical concentration range of gelling agents found in gel?
0.5-2%
what is the difference between a gel and a magma?
gel: two phase system of small discrete particles
magma: relatively large particle size
what do single-phase systems consist of?
organic macromolecules uniformly distributed through a liquid in such a manner that no apparent boundaries exist b/w the dispersed macromolecules and the liquid
what is imbibition?
taking up of liquid without an increase in volume
what is swelling?
taking up of liquid with an increase in volume
what is syneresis?
when the interaction between particles of the dispersed phase increases on standing and the dispersing medium is squeezed out as droplets and the gel mass shrinks
what is thixotropy?
reversible change from sol to gel
what is a xerogel?
formed when a liquid is removed from the gel and only the framework remains
what are some uses of gels?
preparing oral, topical, nasal, and ophthalmic and vaginal formulations
what are the 4 main categories for gels?
inorganic
hydrogel
organic
organogel
what is a main difference between organic and inorganic gels?
inorganic - two phase system
organic - one phase system
give an example of an inorganic gel and an organic gel
inorganic - aluminum hydroxide gel, bentonite magma
organic - tragacanth, carbomer
what is characteristic of the ingredients found in hydrogels?
ones dispersible as colloids or are soluble in water
what kind of ingredients are found in organogels?
hydrocarbons like mineral oil hydrocarbon waxes
fats (lards, cocoa butter)
soap base greases (Al stearate)
what are jellies?
gels in which the structurally coherent matrix contains water (with active drug) and a thickening agent
what could be some thickening agents found in jellies?
tragacanth
gelatin
carboxymethylcellulose
what are two ways of avoiding microbial growth in jellies?
antimicrobial preservative
stored in fridge
how do you prevent evaporation of water in jellies?
stored in a closed container
what is a problem with preparing gels (esp. organic polymers)?
wetting the powder
the powder usually forms clumps and the interior of the clump remains dry, taking a long time for the material to hydrate
how do you overcome the problem with wetting the powder?
slowly adding the dry powder in portions with aggressive mixing to disperse the powder and allow the small particles to hydrate
what is a second technique to overcome wetting the powder?
disperse powder in a medium in which it is insoluble and then add the dispersed powder to the solvent with mixing
what are some examples of mediums that could be used to disperse the powder?
alcohol
glycerin
proplyene glycol
what is alginic acid?
gelling agent obtained from seaweed
usually tasteless
what concentration range is used for alginic acid?
1-5%
what happens when soluble calcium salt is added to the dispersion with alginic acid?
cross-linking occurs and the product becomes much more viscous
what is bentonite?
colloidal hydrated aluminum silicate which is insoluble in water but swells to ~12x its volume in water to form a gel
what makes bentonite good to use in gels?
thixotropic
forms of a sol when shaken which allows easy and rapid dispersion of suspension particles and easy pouring for administration
what is a bad thing about bentonite?
it is alkaline and may pose stability problems for an added medication
if it’s acidified, it loses its viscosity
what can carbomer/carbopol resins be used for?
thickening, gelling, emulsifying or suspending agents
what happens when a carbomer is added to an alkali?
neutralizes with the alkali and forms a very viscous product
what can you neutralize aqueous dispersions with? hydroalcoholic dispersions?
aqueous - NaOH
hydro - triethanolamine
what use is poloxamer at concentrations of 15-50% in water?
it forms gels which are stable in the presence of acids, alkalis and metal ions
what name are poloxamers marketed under? what are they mainly used for?
Pluronic
used as topical drug delivery systems
what auxiliary label should be on all disperse system containers?
shake well before use
what can a pharmacist do to ensure proper shaking of the disperse system?
provide disperse system in oversized container so shaking can be effective
what is the usual concentration of surfactants in a dispersion system?
5%
