Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Dosage Forms II > Exam 1 Suspensions > Flashcards

Exam 1 Suspensions Flashcards

1
Q

What is a suspension?

A

a liquid preparation that consists of solid particles dispersed throughout a liquid phase in which the particles are not soluble → like solid drug particles suspended in water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why would a suspension be preferred over a solution?

A
  1. solubility
  2. chemical stability → if unstable, it’s better if formulated as a suspension since suspensions follow zero order kinetics (more constant degradation) while solutions follow first order kinetics (exponential decay curve)
  3. palatability (taste) → example is that erythromycin estolate oral suspension is more palatable than erythromycin solution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why would a suspension be preferred over a tablet dosage form?

A
  1. flexibility of dose
  2. ease of swallowing
  3. dissolution rate → suspension already has the drug disintegrated into small particles compared to waiting for the tablet to be broken down
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why are suspensions better than other dosage forms in some cases?

A
  1. compared to tablets, the drug is better dissolved as a suspension since the drug is already broken down into small pieces → faster dissolution rate
  2. compared to tablets, the drug is excreted faster since it is absorbed faster whereas with the tablets, it takes the longest because the tablet needs to disintegrate and be broken down → takes time
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why are suspensions better than other dosage forms in some cases?

A
  1. compared to tablets, the drug is better dissolved as a suspension since the drug is already broken down into small pieces → faster dissolution rate
  2. compared to tablets, the drug is excreted faster since it is absorbed faster whereas with the tablets, it takes the longest because the tablet needs to disintegrate and be broken down → takes time
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the components of a suspension?

A
  1. active ingredient (solid particles) → the drug
  2. vehicle → continuous phase (dominant phase), usually water
  3. buffer → to keep a certain pH to keep the drug stable
  4. preservative
  5. flocculating agent
  6. structured vehicle system
  7. wetting agent
  8. antifoaming agent
  9. flavor and sweetener
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the desirable properties of a suspension?

A
  1. the suspended material should not settle rapidly → if it settles too quickly, bad things can happen especially if the patient does not shake before use
  2. the particles that settle to the bottom of the container must not form a hard cake but should be readily redispersed into a uniform mixture when the container is shaken
  3. easy to administer → must not be too viscous to pour freely from the orifice of the bottle or to flow through a syringe needle & in the case of an external lotion, must be fluid enough to spread easily over the affected area and yet must not be so mobile that it runs off the surface to which it is applied to
  4. particle size remains constant during storage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the correlation between particle size and dissolution rate?

A

dissolution rate is a measure of particle size so if particle size is not constant, dissolution rate changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How is settling measured?

A

using Stokes Law in which V is the velocity of sedimentation, d is diameter of particle in cm, ps is density of the solid, pl is the density of the liquid, n is the viscosity of liquid (example water is 1 centipoise which is 0.01 poise) and 980 is the gravity constant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How can settling time be changed?

A
  1. changing the particle size → if particle size decreases, settling time increases
  2. changing the solution from water to sorbitol → sorbitol has a greater density and viscosity so the settling time increases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the typical size range for particle size in suspensions?

A

1-50 micrometers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the different ways to make particle size smaller?

A
  1. micropulverization
  2. fluid energy grinding
  3. spray drying
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is micropulverization?

A
  1. makes particle size of 10-50 micrometers (for most oral and topical suspensions)
  2. high speed attrition or impact mills
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is fluid energy grinding?

A
  1. makes particle size <10 micrometers (for parenteral like IM or SC or ophthalmic suspensions that cause little to no sensation in the eyes)
  2. jet milling, micronizing
  3. shearing action of high velocity compressed airstrear (airstream?) on the particles in a confined space
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is spray drying?

A
  1. makes particle size <5 micrometers → important for lung delivery
  2. spray dryer: a cone shaped apparatus into which a solution of a drug is sprayed and rapidly dried by a current of warm, dry air circulating in the cone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the two main things in a suspension formulation design?

A
  1. the dispersed phase (solid particles)

2. the dispersion medium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the three different types of suspensions?

A
  1. dispersed suspension
  2. flocculated suspension
  3. structured vehicle system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the thermodynamic stability of suspensions?

A
  1. given by the equation ΔG = γs/l*ΔA in which ΔG is the increase in surface free energy, γs/l is the interfacial tension between solid and liquid, and ΔA is the increase in surface area
  2. a suspension is stable when ΔG = 0 which can never be reached in a suspension because we want small particles (high ΔA) for rapid dissolution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does a suspension move toward ΔG = 0 over time?

A

by two processes that reduce the surface area (ΔA) which is another way of saying increasing the particle size → aggregation and crystal growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the four different types of interparticle forces?

A
  1. van der waals attractive force
  2. hydration repulsive force
  3. electrostatic repulsive force
  4. steric repulsive force
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are van der waals attractive forces?

A

operates at a moderate distance from the surface but becomes very strong close to the surface → increases as distance gets smaller → formulation factors DO NOT affect van der waals force

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are hydration repulsive forces?

A

due to absorbed water molecules at the surface of a particle → formulation factors DO NOT affect the hydration repulsive force

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are electrostatic repulsive forces?

A

due to surface charge on the particles → may be controlled by the formulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are steric repulsive forces?

A

due to an absorbed layer of neutral polymer at the surface of a particle → may be controlled by the formulation

24
Q

What forces are driven by the drug itself and we cannot do much about it?

A
  1. van der Waals attractive force

2. hydration repulsive force

25
Q

What forces can be controlled by modifying the formulation?

A
  1. electrostatic repulsive force

2. steric repulsive force

26
Q

What is the difference between repulsive and attractive forces?

A
  1. repulsive forces (+) decrease as there is more distance between particles
  2. attractive forces (-) decrease as particle distance increases
27
Q

What happens in a dispersed suspension?

A
  1. want to make repulsive forces dominant
  2. the particles repel each other and do not aggregate (but if the particles get really close, they will act like a magnet and stick to each other)
  3. the problem → particles settle as individual particles which leads to a dense, compact sediment (cake) which is difficult to resuspend → once the particles get close together and settle, they will form that dense cake layer
28
Q

What happens in a controlled flocculation?

A
  1. repulsive and attractive forces are in balance
  2. particles are attracted to each other at the secondary minimum to form aggregated which are known as floccules → floccules settle to produce a sediment with a high volume which is easy to redisperse
29
Q

What is the secondary minimum in a controlled flocculation?

A

the certain level of distance between the two particles that can be broken apart with minimum forces and that the particles are okay/comfortable with (won’t repel or attract one another)

30
Q

What are the differences between dispersions and flocculations?

A
  1. dispersion: want to keep the particles away from each other so they don’t settle and form a cake, all particles are on their own, supernatant will not be clear (hazy), once the particles settle, they form a cake that is compact and difficult to break up
  2. flocculation: has some distance between the particles (secondary minimum) and they form aggregates called floccules that settle fast but are less prone to compaction and can be broken up easily, supernatant is clear/transparent, can be easily redispersed since there is the space between the particles, has a loose sediment (aka floccules) with a larger volume
31
Q

What is sediment volume (F) and degree of flocculation (β)?

A
  1. sediment volume (F) = final volume of sediment/volume of suspension (is a unitless ratio) → the greater the sediment colume, the greater the flocculent suspension1.
  2. degree of flocculation (β) = sediment volume of test suspension (aka flocculated suspension)/sediment volume of dispersed suspension
    FLOCCULATED SUSPENSION WILL TYPICALLY HAVE LARGER SEDIMENT VOLUME!!!
32
Q

What are flocculating agents?

A
  1. the choice depends on the type of drug and type of product desired
  2. clay (diluted bentonite magma) → oral suspension
  3. alteration in the pH of the suspension (to the region of minimum drug solubility) → parenteral solution
  4. electrolytes → reduces the electrical barrier between the particles by masking the surface charges to make it more neutral
  5. non-ionic or ionic surface active agents → to control repulsive interactions
  6. same charge = repel, no charge = no interaction, no repelling
33
Q

What happens when you use KH2PO4 (monobasic potassium phosphate) as a flocculating agent?

A

starts out with a dispersion (all positive charges) → the addition of KH2PO4 turns it into a flocculated suspension (with a mix of positive and negative charges) → if you keep adding KH2PO4, will make it negatively charged and back to a dispersion once again

34
Q

Even if it’s possible to resuspend floccules, why is it not desirable that a suspension settles too rapidly?

A
  1. can hinder accurate measurement of dosage

2. esthetically not good

35
Q

What is a structured vehicle?

A
  1. thickens the dispersion medium and helps suspend particles
  2. should not interfere with the availability of the drug
  3. should not make the suspension too viscous to agitate or to pour
36
Q

What are some examples of structured vehicles?

A
  1. polymer → carboxymethylcellulose (CMC), methylcellulose, microcrystalline cellulose, polyvinyl pyrrolidine, xanthan gum
  2. clay → bentonite, magnesium aluminum silicate
37
Q

What is rheology?

A

the study of flow characteristics which consists of shear rate and shear stress in which force is applied from the side and the top part moves faster than the bottom (has drag) →

  1. shear rate (dv/dr) → the difference of velocity (dv) between two planes of liquid separated by a distance (dr) → basically how quickly the liquid is willing to flow
  2. shear stress (F) → the force per unit area (F’/A) required to bring about flow → basically the force applied to the liquid
38
Q

What are the two different types of flow?

A
  1. Newtonian flow (direct linear relationship, straight upwards linear line)
  2. Non-Newtonian flow → plastic (nothing flowing for a little then curved upwards and then straight upwards linear line), pseudoplastic (like exponential upwards curve where applying greater force/shear will result in faster flow), dilatant (like a saturation curve where more applied stress will result in slower flow)
39
Q

What is the relationship between velocity and viscosity?

A

velocity decreases as viscosity increases (Stokes law)

40
Q

What is Newtonian flow?

A

shows constant viscosity, the slope of the rate of shear vs shearing stress is a positive linear line

41
Q

What are the units for viscosity?

A

cps (centipoise = 0.01 poise in which poise is equal to dynesec/cm^2 which is equal to the units g/(cmsec)) → the viscosity of water is 1 cps

42
Q

What is plastic non-Newtonian flow?

A
  1. is typical of flocculated suspensions
  2. f (yield value) → threshold of shear stress necessary to initiate flow which represents the strength of the attractive force of the secondary minimum
  3. shear thinning → viscosity decreases as sheer rate is applied
  4. slope is shallow then steep → high then low viscosity
43
Q

What is pseudoplastic non-Newtonian flow?

A
  1. typical of polymer solutions such as methyl cellulose, polyvinyl alcohol, sodium carboxymethylcellulose, xanthan
  2. shear thinning → viscosity decreasing as sheer rate is applied
  3. slope is shallow then steep → high viscosity then low viscosity
44
Q

What is dilatant non-Newtonian flow?

A
  1. exhibited by suspension having a high solids content
  2. shear thickening → viscosity increases as sheer rate is applied
  3. steep slope then shallow slope → low viscosity then high viscosity
45
Q

What is thixotropy? (thixis = stirring, shaking & trepo = turning, changing)

A
  1. the ability of a system that was disturbed by an applied shear stress to return to its undisturbed structure
  2. plastic and pseudoplastic (shear thinning) fluids show this change in viscosity
  3. at rest, the fluid forms a rigid matrix that resembles a gel which will stabilize suspensions
  4. as shear is applied by shaking, the matrix relaxes and forms a sol with the characteristics of a liquid dosage form for ease of use
  5. upon removal of the stress, the sol is returned to the undisturbed gel structure
46
Q

What is the basic takeaway of thixotropy?

A

at rest the fluid is like a solid but when shaken it is like a liquid → the ability of the system to go back to its undisturbed nature when it is disturbed

47
Q

What are the main points of a dispersed suspension (Stokes law approach)?

A
  1. aim to achieve a very slow rate of sedimentation → want to keep the particles repelling as much as possible
  2. cloudy suspension
  3. dense sediment (aka cake)
  4. may form a non-suspendable sediment since it is a dense cake
48
Q

What are the main points of a controlled flocculation?

A
  1. takes advantage of the secondary minimum
  2. rapid rate of sedimentation
  3. clear supernatant
  4. large sediment volume
  5. easily redispersed by shaking
49
Q

What are the main points of structured vehicle suspension?

A
  1. may appear as a semi-solid when undisturbed but is fluid when shaken → fluid with shear stress and semi-solid when stored/at rest
  2. no sedimentation
  3. thixotropic → reversibility between thick and thin viscosity
50
Q

What are the different strategies to make different suspensions?

A

particles → (addition of wetting agent and dispersion medium) → uniform dispersion of deflocculated particles → A, B or C
A: (incorporation of a structured vehicle) → deflocculated suspension in structured vehicle as final product
B: (addition of flocculating agent) → flocculated suspension as final product
C: (addition of flocculating agent) → flocculated suspension → (incorporation of structured vehicle) → flocculated suspension in structured vehicle as final product

51
Q

What is the main takeaway of the multiple alternative approaches to the formulation of suspensions?

A

can’t rely on a single strategy → can use a mix of strategies

52
Q

What is wetting?

A

the displacement of air from the surface of a particle by the vehicle (aka get rid of air bubbles) → have to consider water-based (aqueous) vehicle and hydrophilicity (like water) or hydrophobicity (like oil) of the drug particles

53
Q

What happens when a drug particle is suspended in liquid?

A

the drug particle can be smooth or rough but if it is rough, will have air bubbles (since it is hydrophobic and hard to wet) → so need to reduce the surface tension of water by adding surfactants that can spread and wet the particle

54
Q

What is the idea behind the contact angle?

A

a high contact angle indicates poor spreading and that the cohesive forces of the liquid is strong

55
Q

Organic solvents typically have higher or lower surface tension?

A

lower surface tension → can spread better

56
Q

What is the relationship between contact angle and hydrophilicity of a solid?

A

contact angle greater than 90 degrees → hydrophobic

contact angle less than 90 degrees → hydrophilic

57
Q

What is the idea behind using a wetting agent?

A

if a solid has a rough surface with small pores, the aqueous vehicle will not enter the pore so it will remain filled with air so the particles will float → best solution is to reduce the surface tension of the aqueous vehicle to allow the water to enter the pore and displace the air → surface active agent (surfactant) is added to reduce the surface tension = wetting agent

58
Q

What are some examples of wetting agents?

A

polysorbate 80 (aka Tween 80)

Dosage Forms II (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions