Pharmaceutical Suspensions

What’s a suspension ? • Defintion• Dimentions(0.5-10) (1-10) (10-50)• Good Suspension (10-50), Why?• Both kinds:

o Oral Suspensionso For Oral SuspensionWhy called dry syrups?

What’s a suspension ? • Dose• 5 mL teaspoonful• Dropper

Suspension Requirements• Settling?• How redispersed?• Changes in The particle size?• How pouring?

Why a suspension?

•Advantages• Liquid Therapy!• What about Chemical Stability?• What about (infants, children, and the elderly) ?• What about taste?

Why a suspension?

•Disadvantages• What about stability and skills required?• What about shelf-time?• Appearapnce ?• Carry with pateint?

• Note that:, erythromycin estolate

Stability;

• Is it perfect to repersent a Suspension?

Stability;

• So it’s an Indication• Dicussing all factors affecting the stability, including:• Particle size

• Density (floating vs. sedimentation)• Viscosity

• Note that: It’s not appropriate to a suspension to float??

• It’s not appropriate to have too much fine powders??

HOW TO MAKE A FINE POWDER? (10-50 MICRON)• Micropulverization?---attrition mills • Still finer powder? Fluid energy, what size?• How?• high-velocity compressed airstreams.• confined space!

Fluid Energy

sonic and supersonic velocities of the airstreams

Preparing Flocculated suspensions

Preparing Flocculated suspensions

Preparing Flocculated suspensions• Definition• less rigid or loose aggregation!!• flocs settle more rapidly than fine ????• weak particle-to-particle bonds• higher sediment volume• distribute readily

Preparing Flocculated suspensions

• diluted bentonite magma. flocculating agent

• pH: minimum solubility

• Electrolytes can also act as flocculating agents

• The carefully determined concentration of non-ionic and ionic surface-active agents (surfactants) can also induce flocculation

Bentonite

Formulation considerations for orally administered suspension:• Physical properties of the therapeutic Agent:• Particle size

• Crystallisation • Hydrophilic polymers to solve the proplem.

• Particle Shape:• i.e.: The needle-shaped particles formed a tenacious sediment cake on standing

that could not be redistributed, whereas the barrel-shaped particles did not cakeupon standing.

Formulation considerations for orally administered suspension:

• Wetting properties of the therapeutic agent• interfacial tensions should be decreased• poorly wetted, will tend to aggregate

Poorly wetted prticles

Aggregation

Rheology• Imagine a suspension you cant pour it down!!!• Imagine it fast to sedimentate.• Let’s discover rheology by food!!

Rheology for Pharmacists Year 4

Rheology

• Newtonian Systems:

Rheology

• Newtonian Systems:

Rheology

• Pseudoplastic Systems:

Rheology

• Pseudoplastic Systems:• i.e.: Veegum Magma (2%)

Rheology

• Pseudoplastic Systems:• i.e.: Veegum Magma (2%)

• Thixotropy system

Rheology

• Dilitant flow Systems:

Toothpaste

Rheology

• Dilitant flow Systems:• i.e.: stratch gel.

Rheology• Compare them:

And Now?Are u still Ready?

Excipients used in the formulation of suspensions for oral administration:

• Vehicle:• Most common is

• It is prepared by distillation, ion exchange methods or by reverse osmosis

• i.e.: Citric/Citrate of veicles:• Acidity, Alkanity? Electrolytes? Taste?

• Our product. Citric/citrate which lead to pH=5.5• Although it’s not the appropriate to minimum stability

Excipients used in the formulation of suspensions for oral administration:

Pay Attention

Excipients used in the formulation of suspensions for oral administration:

 

Note that: a liquid suspension for a neonate should not include preservatives, colorings, flavorings, or alcohol because of the potential for each of these to cause either acute or long-term adverse effects. 

Excipients used in the formulation of suspensions for oral administration:

• Excipients to enhance the physical stability of Suspensions:• Addition of electrolytes• (Brownian, Steric, and Electrostatic vs. Vandeer Vals)

Excipients used in the formulation of suspensions for oral administration:

Excipients used in the formulation of suspensions for oral administration:

• Surface-active agents:• Effect on wetting

Excipients used in the formulation of suspensions for oral administration:

• Effect on flocculation• ionic or non-ionic polymers? And why?

• Consider oral preps and Safety.•

e.g. polyoxyethylene fatty acid sorbitan esters, sorbitan esters or lecithin

Zeta Secondary minimum

Excipients used in the formulation of suspensions for oral administration:

• Effects on the physical stability of suspensions:

stearic repulsion

1 2

3 4

Polymer Distance

•Note That:• It reduces repulsion on far distance (stearic repulsion) but

enhance it on far distance (reduces zeta potential)• Next example clarifies the idea.

Excipients used in the formulation of suspensions for oral administration:

• Polymer Effect depends on the following:• Concentration:

• enhances repulsion but does not prevent the interaction of the particles in the secondary minimum

xx

xx Flocculation

Best Distance

Excipients used in the formulation of suspensions for oral administration:

• Polymer Effect depends on the following:• The type of polymer:

• This ability to interact may effectively maintain the polymer-coated particles at a distance, resulting in the production of a structured floccule

stearic repulsion

Excipients used in the formulation of suspensions for oral administration:

• Polymer Effect depends on the following:• Effect on the rheological properties of oral suspension:• concentrations ˃0.01%: (oral suspensions)• Pseudoplatic system -thixotropy

Excipients used in the formulation of suspensions for oral administration:

• Examples:• MC, HEC, HPMC, sodium CMC• Polyvinylpyrrolidone• Acacia, tragacanth and xanthan (caution)• Bentonite

Tired of presentation?Let’s have a break!

Relaxed?Let’s continuewith the excipient

Excipients used in the formulation of suspensions for oral administration:

• Preservatives and mold growth:• Is the mold growth allowed?• How much?• What’s prevented?

• Examples

Excipients used in the formulation of suspensions for oral administration:

• Sweetening agents/flavours• Compliance?

• aesthetic properties?• i.e.: sorbitol

• Antioxidants• Stability?

■ i.e: sodium sulphite

Some subdosage forms of suspensions• DRY POWDERS FOR SUSPENSIONS:

• i.e.:Antibacterial , stability?• Antacid Oral Suspensions• RECTAL SUSPENSIONS. • Antibacterial Oral Suspensions

Some subdosage forms of suspensions

Sustained-Release Suspensions (Pennkinetic):

granulate

Ion exchage

Ionized drugEC

Some subdosage forms of suspensions

Sustained-Release Suspensions (Pennkinetic):

granulate

Ion exchage

Ionized drugEC

Extemporaneous Prepration:

Contact the supplier