Colloids and suspensions

what is a dispersed system

one or more ocmponents dispersed as particles or droplets throughout another component

• 2 phases vs solutions have 1 phase

what are colloidal dispersions and the size of their particles

dispersions where size of dispersed particles are between 10^-9 and 10^-6 m

• suspension particle size >1 um vs colloidal system particle size < 1um

why are suspensions used in formulation of drugs (ie. pros of suspensions over solutions)

• taste-masking

• not possible to dissolve drug completely within a reasonable volume

• drug may be more stable

• poorly soluble drugs cannot be made into solutions

• prevent degradation - hydrolysis of drug by water

• drug may be more stable as a solid so it is dispersed before dispensing into a suspension

properties of good suspensions

• particles are small and the same size

• homogenous - needs to be evenly distributed throughout the liquid to ensure same dose is given

• easy to disperse upon shakinh

what type of properites allows solutions and suspensions to be differentiated

optical properties

what is the Tyndall effect

light scattering by particles in a colloid

• light scattering makes the colloidal systems look cloudy/ turbid

true or false: in suspension particles scatter beam of light so path can be seen

true: whereas in solutions, there is very little scattering so path of beam cannot be seen

true of false: the less I (turbidity), the less turbid the sample is so the lower the conc of dispersed particles

false: the less I (turbidity), the more turbid the sample is so the greater the conc of dispersed particles

• I = I_o e^-IL

  • where I_o = light intesitiy entering system

  • I is light intensity exiting system

  • L = length of sample

particles in colloids will undergo Brownian motion, what is Brownian motion

random movement of dispersed particles throughout the continuous phase

what is the equation for diffusion in colloids

Fick’s Law:

dm/dt = -DA [dc/dx]

which equation is used to determine velocity of sedimentation

Stoke’s Law

V = 2a²g (sigma - p)/ 9n where:

• a = particle radius

• sigma = density of solid particle

• p = density of liquid

• n = viscosity of liquid

• g = acceleration due to gravity

what is the equation for sediment ratio

• R = height of sedimented layer/ initial height of suspension or

• R = volume of sedimented layer/ total suspension volume

when making suspensions, what do you add if drug is insoluble in water. how did this agent work

add wetting agents which break down interfacial tension so solid particles are dispersed easily in liquids

• liquid needs to be spread around solid for good suspension

what is the interfacial tension

energy barrier which prevents liquid spreading around solid

examples of wetting agents

surfactants, hydrophilic colloids, solvents

clumping → dispersed is achieved when wetting agent is added to clumping state. what is clumping and what happens when you add wetting agents

• clumping is when particles stick together

• increasing wetting of hydrophobic drug particle leads to decrease in surface tension

clinging → dispersed is achieved when wetting agent is added to clumping state. what is clinging and what happens when you add wetting agents

• clinging is when particles adhere (stick) to the container

• wetting agents decrease adsorption of particles to container by applying repellent coating

what is aggregation

collection of particles in groups

aggregation of particles in colloids lead to

• flocculation (temporary - particles easy to separate)

• deflocculation (permanent - difficult to separate)

what is coagulation

when particles are closely aggregated and difficult to redisperse (defloculated systems)

what are flocculation systems

aggregates that have loose structures and particles have a small distance apart and weakly bound in groups

what is caking and what does this mean in terms of dosing

formation of densely packed, non-dispersible layer of aggregates (particles) at the bottom of container that cannot be dispersed again upon shaking

results in patient underdosing (first few doses = no drug) or overdosing (too much drug if taken from the bottom)

true or false: caking cannot be eliminated by reduction in particles size or by increasing viscosity of continuous phase

true: refer to Stoke’s Law

how to reduce caking (hint: want to increase viscosity)

add viscosity enhancer agents which increases viscosity

• sedimentation rate (from Stoke’s Law) is slowed

• however, caking will still eventually occur with viscosity enhancers

how does flocculating agents reduce caking

• encourage floc formation to minimise caking

what creates an electrical double layer in colloidal systems

the electrostation interactions between drug particles and positively or negatively charged ions

flocculation depends on DVLO theory: what does this predict

• predicts the stability of charged particles in dispersion to aggregation

• V_T = V_A + V_R

• V_R (potential energy of repulsion) determines whether partially deflocculated system is stable or not

• V_A potential energy of attraction

• V_T = total potential energy of interactions

stage 1 of DVLO theory: all particles have a net surface charge

• means particles will stay apart

• there are counter ions in suspension which will cancel out the surface charges

stage 2 of DVLO theory: encouraging floc formation by controlling net surface charge

• use zeta potential to measure how strong repulsion forces are between 2 particles

true or false: the less counterions, the lower the zeta potential

false: the more counterions, the lower the zeta potential because charge cancels out more quickly

can zeta potential be negative and if so when does this occur

yes, when there are too many counterions

what is the ideal zeta potential

want to be close to zero

stage 3 of DVLO theory: what does the diagram look like

what value of zeta potential will caking occur and not occur

• -30 → +30 mV flocs form so no caking

• < -30mV or >+30 mV means it is dispersed to caking forms

stage 4 of DVLO theory: what does Vr depend on

• surface charge

• thickness of double later

• Vr affects height of primary maximum and depth of secondary minimum energies

what happens to particles if primary maximum is:

• large

• small

• particles stay dispersed

• particles will aggregate

stage 5 of DVLO theory: adding electrolytes (counterions), what will this do

• increase Debye-Huckel parameter

• decrease thickness of electrical double layer

• decrease zeta potential

• increase depth of secondary minimum

• THIS ALL LEADS TO FLOCCULATION

will increasing electrolyte conc prevent caking and why

yes, because secondary minimum occurs lower on the graph

• zeta potential is close to zero → leads to more flocculation

true or false: too much electrolyte can lead to caking

true

changing amount of electrolye will change what

surface charge of drug particle

difference between viscosity enhacing agents and electrolyes

viscosity enhancing agents SLOW down caking process

vs

electrolytes prevent caking

to prevent caking, surfactants are added. what does this do

neutrailises surface charge so repulsion is reduced

adding polymers (chemical groups which interact with particle surface) prevent caking, how does this work

free end of the polymer attaches to another particle and leads to interparticle bridging and flocculation

• if there is no particles to interact with, free end of polymer coats the particle which leads to restabilision and deflocculated system

difference between flocculation and deflocculation

in floc vs defloc:

• aggregates settle quickly vs sedimentation rate is slowed

• liquid is entrapped in sediment so easily redispersed vs slow rate of settling prevents liquid entrapment so compact structure formed (caking), difficult to redisperse

compare properties of flocculated vs deflocculated system

flocculated: particles settle [quickly/slowly] leading to [tightly/loosely] packed sediment with [large/small] volumes of entrapped liquid. this means it is '[difficult/easy] to redisperse

deflocculated: particles settle [quickly/slowly] leading to [tightly/loosely] packed sediment with [large/small] volumes of entrapped liquid. this means it is '[difficult/easy] to redisperse

flocculated: particles settle [quickly/slowly] leading to [tightly/loosely] packed sediment with [large/small] volumes of entrapped liquid. this means it is '[difficult/easy] to redisperse

deflocculated: particles settle [quickly/slowly] leading to [tightly/loosely] packed sediment with [large/small] volumes of entrapped liquid. this means it is '[difficult/easy] to redisperse

why are viscosity enhancing agents useful

they increase viscosity so decrease sedimentation rate

stokes law states that rate of sedmentation is proportion to 1/viscosity