routes of administration (oral suspensions)

Question 1

what is a pharmaceutical suspension

Answer 1

a liquid disperse system consisting of particles distributed within a liquid vehicle
classified as a coarse or colloidal dispersion, depending on the size of particles (normally between 0.1 and 10 micrometers)
suspensions are not optically clear and appear cloudy

Question 1

what is a disperesed system

Answer 1

a two-phase heterogenous system in which an insoluble or immiscible dispersed phase is distributed through a continuous phase

Question 2

reasons for forumulating of an oral pharmaceutical suspension

Answer 2

to deliver poorly water-soluble which cannot be formulated as aqeous solutions
to mask the bitter taste of the drug
to increase drug stability
to achieve controlled/ sustained drug release

Question 3

flocculated systems

Answer 3

suspended particles are formed into floccules (van der Waals forces) rather than separate particles
sediment will be large and the redispersion is easy
controlled flocculation is a mechanism to prevent particle caking in suspension formulations
reducing the surface charge of particles can induce flocculation which can be achieved through the addition of surfactant and ionic salts

Question 4

deflocculated systems

Answer 4

a system where particles are individually and uniformly dispersed throughout the liquid medium
it will remain deflocculated when repulsive energy between the suspended particles is high

however, deflocculated particles may settle slowly over time results in the formation of a layer of particle sediment at the bottom of the suspension which will be difficult to re-suspend

not ideal as pharmaceutical suspensions

Question 5

how to control stability of suspensions

Answer 5

place particles easily
particles are readily uniformed and uniformly re-dispersed
particle size remains consistent over time
viscosity is high enough to ensure a uniform dose, but not so viscous that the suspension cannot be easily poured from the bottle

Question 6

what causes particle movement in suspensions

Answer 6

Brownian motion
gravity
external agitation

in deflocculated systems, particles behave as individual small particles
in flocculated systems, particles clump together and behave as individual large particles with a porous structure

Question 7

what is brownian diffusion

Answer 7

small particles are subject to Brownian motion only smaller than 2 micrmeteres

irregular movement within the medium
diffusion from high concentration to low

provides more homogenous particle distribution
smaller particles will diffuse more rapidly
increasing medium viscosity will also reduce diffsuion

Question 8

sedimentation

Answer 8

downward particle movement due to gravity
, particle movement is critical for successful suspension formulation

Question 9

sedimentation speed

Answer 9

• The speed of sedimentation and reversibility are two key factors.
  – A slow sedimentation rate would be optimal a deflocculated system.
  – Reversibility is required to ensure dosing is reproducible – a flocculated system would be better.
• Either develop a deflocculated system with minimal sedimentation which will require greater viscosity to maintain dispersion.
• Or develop a flocculated system with controlled slow sedimentation.

Question 10

relationship between particle size and sedimentation

Answer 10

particle size has a direct effect on the ease of maintenance of a uniform suspended phase
* Submicron suspension: Brownian motion helps to keep the particles in a dispersed state.
* Larger particles: the effect of gravity becomes significant.
* According to Stokes’ law, the velocity of a suspended particle falling under gravity is directly proportional to the particle’s size

Question 11

ways to reduce sedimentation rate

Answer 11

• Particle size reduction – increases diffusion.
• Reduce particle density – but at the same time increases particle size thus may have adverse effects.
• Increase medium density – e.g. adding dextrose.
• Increase medium viscosity – e.g. adding polymers like hydroxypropyl methylcellulose, reduces both diffusion and sedimentation.
• Increase temperature – increases diffusion constant, but effect is limited within normal range of temps

Question 12

what is zeta potential

Answer 12

provides a measure of the magnitude of the electrostatic or charge repulsion/attraction between particles at the slipping plane, between the particle and its associated double layer and the solvent

Question 13

look at slide 22/23

Answer 13

okay cuh

Question 14

what happens when the zeta potential is reduced below a certain value

Answer 14

• If the zeta potential is reduced below a certain value, the attractive forces between particles due to van der Waals’ force, overcome the forces of repulsion and the particles come together to form floccules.
• If a suspension has a large negative or positive zeta potential, the particles within it tend to successfully repel each other

Question 15

effect of excipients on electrical double layer

Answer 15

ionic salts increase the number of mobile charges
at low concentrations only the diffuse layer is affected ted, easier to neutralize the particle charge, thinning diffuse layer
at higher concentrations will also affect the fixed layer- charge on the particle surface will decrease

Question 16

effects of surfactants on electrical double layer

Answer 16

critical micelle concentration is the concentration of surfactants above which micelles form

above CMC micelles form with hydrophobic care in which hydrophobic drugs may dissolve

below CMC, surfactants will cover the particle surface. to reduce interfacial tension between particle and liquid medium (enhance suspension stability) surfactants are used at concentrations below CMC

Question 17

excipients to improve palatability (flavors, sweeteners and colorings)

Answer 17

– Improve patient acceptability and palatability.
– Drugs in suspensions formulations are less in tense in taste than in solutions.
– Traditionally sucrose was used as sweetener but potential issues with dental caries and diabetic control.

Question 18

flocculating agents

Answer 18

Decrease zeta potential of the suspended charged particle causing aggregation (flock formation) of the particles.
*The final excipient added to the formulation.
*Examples:
*They are ionic materials e.g. NaCl or CaCl2.
*Surfactants
*Polymeric agents
*Sulfate, citrates, phosphates salts

Question 19

chemical stabilisers and wetting agents

Answer 19

• Chemical stabilisers
  – Improve chemical stability of the drug, this includes:
  – Antioxidants e.g. ascorbic acid at 0.2%w/v.
  – Chelators e.g. disodium salt of EDTA.
• Wetting agents
  – Reduce interfacial tension between particle and liquid medium.
  – Improve homogeneity of drug particle distribution.
  – E.g. using surfactants below their critical micelle concentration.